Coexistence of Autoimmune Thyroiditis and Juvenile Idiopathic Arthritis.
Autoimmune thyroid disease seems to occur more often in children with juvenile idiopathic arthritis (JIA) than in the general pediatric population. We investigated the prevalence of autoimmune thyroiditis (Hashimoto's thyroiditis) in young patients with JIA in Greece, which has not been evaluated previously. This descriptive study included patients with JIA followed up at the Pediatric Rheumatology Unit of the Second Department of Pediatrics of a tertiary general hospital in Thessaloniki, Greece. All patients were diagnosed and sorted according to the classification criteria of the International League of Associations for Rheumatology. The presence of thyroid autoantibodies was considered for determining autoimmune thyroiditis. Basic demographic, clinical, and laboratory data were collected from patients' records. Results: The analyzed sample comprised 130 patients with JIA (mean age 12.22 years; 69.2% female). Most patients (70%) had a family history of at least one autoimmune disease and 30.8% of Hashimoto's thyroiditis. More than half (53.8%) had enthesitis-related arthritis (ERA), 22.3% had oligoarthritis, and 15.4% had psoriatic arthritis. Thyroid autoantibodies were detected in 22/130 patients (16.9%) suggesting autoimmune thyroiditis; most of these patients were euthyroid, whereas 3/22 (13.6%) had overt hypothyroidism determined by elevated levels of thyroid-stimulating hormone, decreased levels of free thyroxine, and typical ultrasound findings for Hashimoto's thyroiditis. The prevalence of clinical cases of Hashimoto's disease was 2.3%. The prevalence of autoimmune thyroiditis in our JIA cohort is higher compared to the general population and consistent with the previously reported range. Hence, investigation for thyroid autoimmunity should be included in the workup of patients with JIA.


Outcomes After Double-Layer Repair Versus En Masse Repair for Delaminated Rotator Cuff Injury: A Systematic Review and Meta-analysis.
Delamination of rotator cuff tears during arthroscopic shoulder surgery has an incidence of 38% to 92%. Double-layer (DL) repair and en masse (EM) repair are most commonly used in this situation. To compare the clinical results of the DL versus EM repair techniques for delaminated rotator cuff tears using a meta-analysis. Systematic review; level of evidence, 3. We identified relevant studies comparing the clinical results of DL and EM repair for delaminated rotator cuff injuries in the PubMed, Embase, and Cochrane databases after the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The primary outcomes were the Constant score and retear rate. Additionally, we compared other postoperative shoulder functional scores, shoulder range of motion, and visual analog scale (VAS) pain scores between the 2 suture methods using a meta-analysis. The mean difference (MD) was compared for continuous outcomes, and the odds ratios (ORs) were compared for categorical outcomes. Of the 197 studies initially identified, 6 studies were included in this analysis. There were significant differences in the Constant score (MD, 8.64 [95% CI, 4.47 to 12.8]; P < .05) and external rotation (MD, 5.10 [95% CI, 2.63 to 7.56]; P < .05) between the 2 techniques, with DL repair having superior outcomes. No significant differences were observed between the 2 techniques in forward flexion (MD, 0.62 [95% CI, -1.18 to 2.43]; P = .50), VAS pain (MD, -0.03 [95% CI, -0.34 to 0.27]; P = .84), or retear rate (OR, 0.73 [95% CI, 0.37 to 1.41]; P = .35). Results of this review and meta-analysis suggest that DL repair was more beneficial than EM repair in terms of the Constant score and shoulder external rotation in patients with delaminated rotator cuff injuries.


Diagnosing and predicting refractory epilepsy.
Over 30% of people with epilepsy will never achieve remission with antiepileptic drug (AED) therapy. These individuals are often severely disabled by their condition, have an unsatisfactory quality of life, and are at increased risk of sudden unexpected death. Early identification of refractory epilepsy would allow prompt referral to specialist services, where the diagnosis can be confirmed, seizures and syndromes classified, AED therapy optimized, and suitability for surgery assessed. Recent studies suggest that patients with symptomatic or cryptogenic epilepsy, those who experience multiple seizures before AED treatment initiation, and those with febrile convulsions, a family history of epilepsy, or psychiatric comorbidities are least likely to respond to drug therapy. Failure to achieve good seizure control with the first one or two AED monotherapies is usually sufficient to highlight the possibility of subsequent refractory epilepsy. For most of these individuals, combination therapy using AEDs with complementary modes of action is the recommended treatment approach.


A Routine 'Top-Down' Approach to Analysis of the Human Serum Proteome.
Serum provides a rich source of potential biomarker proteoforms. One of the major obstacles in analysing serum proteomes is detecting lower abundance proteins owing to the presence of hyper-abundant species (e.g., serum albumin and immunoglobulins). Although depletion methods have been used to address this, these can lead to the concomitant removal of non-targeted protein species, and thus raise issues of specificity, reproducibility, and the capacity for meaningful quantitative analyses. Altering the native stoichiometry of the proteome components may thus yield a more complex series of issues than dealing directly with the inherent complexity of the sample. Hence, here we targeted method refinements so as to ensure optimum resolution of serum proteomes via a top down two-dimensional gel electrophoresis (2DE) approach that enables the routine assessment of proteoforms and is fully compatible with subsequent mass spectrometric analyses. Testing included various fractionation and non-fractionation approaches. The data show that resolving 500 µg protein on 17 cm 3-10 non-linear immobilised pH gradient strips in the first dimension followed by second dimension resolution on 7-20% gradient gels with a combination of lithium dodecyl sulfate (LDS) and sodium dodecyl sulfate (SDS) detergents markedly improves the resolution and detection of proteoforms in serum. In addition, well established third dimension electrophoretic separations in combination with deep imaging further contributed to the best available resolution, detection, and thus quantitative top-down analysis of serum proteomes.


Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins.
Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.


Stroke unit care in germany: the german stroke registers study group (ADSR).
Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low.


Modulation of chromatin architecture influences the neuronal nucleus through activity-regulated gene expression.
The disruption of chromatin-regulating genes is associated with many neurocognitive syndromes. While most of these genes are ubiquitously expressed across various cell-types, many chromatin regulators act upon activity regulated genes (ARGs) that play central roles in synaptic development and plasticity. Recent literature suggests a link between ARG expression disruption in neurons with the human phenotypes observed in various neurocognitive syndromes. Advances in chromatin biology have demonstrated how chromatin structure, from nucleosome occupancy to higher-order structures such as topologically associated domains, impacts the kinetics of transcription. This review discusses the dynamics of these various levels of chromatin structure and their influence on the expression of ARGs.


Should clinicians incorporate positive spirituality into their practices? What does the evidence say?
Most of the rhetoric decrying the incorporation of basic and positive spiritual care into clinical practice is not based on reliable evidence. We briefly review the current evidence, which demonstrates that (a) there is frequently a positive association between positive spirituality and mental and physical health and well being, (b) most patients desire to be offered basic spiritual care by their clinicians, (c) most patients censure our professions for ignoring their spiritual needs, (d) most clinicians believe that spiritual interventions would help their patients but have little training in providing basic spiritual assessment or care, (e) professional associations and educational institutions are beginning to provide learners and clinicians information on how to incorporate spirituality and practice, and (j) anecdotal evidence indicates that clinicians having received such training find it immediately helpful and do apply it to their practice. We point out the reasons that much more research is needed, especially outcome-based, clinical research on the effects of these spiritual interventions by clinicians. We conclude that the evidence to date demonstrates trained or experienced clinicians should encourage positive spirituality with their patients and that there is no evidence that such therapy is, in general, harmful. Further, unless or until there is evidence of harm from a clinician's provision of either basic spiritual care or a spiritually sensitive practice, interested clinicians and systems should learn to assess their patients' spiritual health and to provide indicated and desired spiritual intervention. Clinicians and health care systems should not, without compelling data to the contrary, deprive their patients of the spiritual support and comfort on which their hope, health, and well-being may hinge.


American social work, corrections and restorative justice: an appraisal.
Social work played an active role in American corrections until the 1980s when the ethic of rehabilitation began to give way to a more conservative doctrine of retribution. Changes in the field of social work, characterized by preference of social workers to work only with certain populations, contributed to social work's diminishment in corrections. Although efforts at rehabilitation continue in corrections, the concept of restorative justice that emphasizes assisting victims, communities, and offenders in dealing with the consequences of crime is gaining acceptance in the field of corrections in the United States and in other countries. This study explored social work's presence in corrections, the decline of that presence, and how the concept of restorative justice can invigorate social work within the field of corrections. Several examples of social work's contemporary efforts to use the concept of restorative justice in the United Kingdom are presented.


Stability and Vapor Pressure of Aqueous Aggregates and Aerosols Containing a Monovalent Ion.
The incidence of charged particles on the nucleation and the stability of aqueous aggregates and aerosols was reported more than a century ago. Many studies have been conducted ever since to characterize the stability, structure, and nucleation barrier of ion-water droplets. Most of these studies have focused on the free-energy surface as a function of cluster size, with an emphasis on the role of ionic charge and radius. This knowledge is fundamental to go beyond the rudimentary ion-induced classical nucleation theory. In the present article, we address this problem from a different perspective, by computing the vapor pressures of (H2O)nLi+ and (H2O)nCl- aggregates using molecular simulations. Our calculations shed light on the structure, the critical size, the range of stability, and the role of ion-water interactions in aqueous clusters. Moreover, they allow one to assess the accuracy of the classical thermodynamic model, highlighting its strengths and weaknesses.


Multimodality Imaging Approach For The Early Diagnosis Boerhaave Syndrome.
Boerhaave's syndrome is a spontaneous transmural rupture or perforation of the oesophagus or post-emesis oesophageal rupture. Boerhaave's syndrome has a high risk of morbidity and mortality, and early, definitive diagnosis leading to prompt management improves outcomes. Definitive diagnosis of this syndrome is made with imaging, including x-ray, USG and computed tomography Scan. This is a case of a 50-year male with history of sudden onset of epigastric pain after an episode of forceful emesis was referred for Ultrasound (USG) abdomen. His USG examination demonstrated fluid collection with internal free floating and linear echoes in left pleural cavity consistent with hemo-pneumothorax his further imaging workup was done with suspicious of Boerhaave's Syndrome which conformed the suspected diagnosis.


Mitochondrial metabolic regulation by GRP78.
Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane. StAR expression and activity are drastically reduced following GRP78 knockdown. StAR folding starts at the MAM region; thus, its cholesterol fostering capacity is regulated by GRP78 long before StAR reaches the mitochondria. In summary, GRP78 is an acute regulator of steroidogenesis at the MAM, regulating the intermediate folding of StAR that is crucial for its activity.


Spatial generalization of learning in smooth pursuit eye movements: implications for the coordinate frame and sites of learning.
We have examined the underlying coordinate frame for pursuit learning by testing how broadly learning generalizes to different retinal loci and directions of target motion. Learned changes in pursuit were induced using double steps of target speed. Monkeys tracked a target that stepped obliquely away from the point of fixation, then moved smoothly either leftward or rightward. In each experimental session, we adapted the response to targets moving in one direction across one locus of the visual field by changing target speed during the initial catch-up saccade. Learning occurred in both presaccadic and postsaccadic eye velocity. The changes were specific to the adapted direction and did not generalize to the opposite direction of pursuit. To test the spatial scale of learning, we examined the responses to targets that moved across different parts of the visual field at the same velocity as the learning targets. Learning generalized partially to motion presented at untrained locations in the visual field, even those across the vertical meridian. Experiments with two sets of learning trials showed interference between learning at different sites in the visual field, suggesting that pursuit learning is not capable of spatial specificity. Our findings are consistent with the previous suggestions that pursuit learning is encoded in an intermediate representation that is neither strictly sensory nor strictly motor. Our data add the constraint that the site or sites of pursuit learning must process visual information on a fairly large spatial scale that extends across the horizontal and vertical meridians.


[Immunogenetic similarity and the distance between Swiss brown cattle and 86 other bovine populations].
By using the frequencies of 43-46 antigens of 9-11 genetic blood group systems in 108145 animals the immunogenetic similarity (r +/- m(r)) and the distance (d) between a Swiss brown cattle and other 86 representatives of the Bovinae subfamily were calculated. The position of Swiss brown cattle on a linear model of the Bovinae family was determined. The position has following indexes: r = 0.7816 +/- 0.0197; d = 0.2181. Phylogenesis of 16 cattle breeds reared with participation of the Swiss brown breed was studied. On the dendrogram these breeds formed two clusters and three branches. The clusters at the bottom of the dendrogram (Swiss brown x brown carpathian) and in the middle (ala-tau x caucasian brown) included breeds reared in the foothills and highlands, and the top of the dendrogram is formed by the lebedin, kostroma breeds and the Tajik type of Swiss brown zebu cattle reared in the flat country.


[Actinic reticuloid. Immunohistochemical study].
A patient that fulfilled the clinical and histological features of actinic reticuloid has been studied. He presented a positive patch test for fragance mix. Typical cutaneous lesions were reproduced with a solar simulator. The immunochemical studies of the inflammatory infiltrates of these induced lesions gave a higher percentage of T8 in relationship to T4 lymphocytes. Most of the cells were HLA-DR positive. No clonality of these lymphocytes was detected. In the peripheral blood lymphocytes, an increased percentage of T8 lymphocytes was also observed.


A Map/INS/Wi-Fi Integrated System for Indoor Location-Based Service Applications.
In this research, a new Map/INS/Wi-Fi integrated system for indoor location-based service (LBS) applications based on a cascaded Particle/Kalman filter framework structure is proposed. Two-dimension indoor map information, together with measurements from an inertial measurement unit (IMU) and Received Signal Strength Indicator (RSSI) value, are integrated for estimating positioning information. The main challenge of this research is how to make effective use of various measurements that complement each other in order to obtain an accurate, continuous, and low-cost position solution without increasing the computational burden of the system. Therefore, to eliminate the cumulative drift caused by low-cost IMU sensor errors, the ubiquitous Wi-Fi signal and non-holonomic constraints are rationally used to correct the IMU-derived navigation solution through the extended Kalman Filter (EKF). Moreover, the map-aiding method and map-matching method are innovatively combined to constrain the primary Wi-Fi/IMU-derived position through an Auxiliary Value Particle Filter (AVPF). Different sources of information are incorporated through a cascaded structure EKF/AVPF filter algorithm. Indoor tests show that the proposed method can effectively reduce the accumulation of positioning errors of a stand-alone Inertial Navigation System (INS), and provide a stable, continuous and reliable indoor location service.


Arhus County Vagotomy Trial: ulcer recurrence rate related to alterations in gastric acid secretion after selective gastric and parietal cell vagotomy.
Clinical and secretory data were analysed with respect to the recurrence rate for 685 patients treated with either selective gastric vagotomy (SGV) or parietal cell vagotomy (PCV) for duodenal ulcer disease. The duration of ulcer history before surgery was of no importance for the recurrence risk. Men with recurrence after SGV were significantly younger than men without recurrence, but no difference was found for women with SGV or for men and women with PCV. The recurrence rate was not higher for hypersecretors (pentagastrin-stimulated peak acid output (PAOpg) greater than 45 mmol/h) than for patients with lower PAOpg. Resting, basal, and stimulated secretion 3 months after surgery were higher for the patients with recurrence than for the patients without, but only a few of the secretion values were significantly different. A higher recurrence rate was found for the patients with the lowest initial acid reduction, and this trend was more pronounced in the PCV group. With regard to the change in gastric secretion during the first year after vagotomy a significant rise was seen for the PCV patients who developed recurrence in spite of initial reduction of more than 60%. For all SGV patients and the PCV patients with an initial reduction on the average or less, the change in secretion capacity had no influence on the recurrence rate. The findings are in accordance with reports about anatomical limitations for a sufficient PCV in about 20% of the patients.


A twelve-week placebo-controlled study of prazosin in the treatment of prostatic obstruction.
Fifty-eight normotensive patients with benign prostatic hyperplasia and maximum urinary flow rates of less than 15 ml/s were randomly assigned to receive a 12-week course of treatment with prazosin or placebo in a double-blind parallel group trial. Prazosin was administered orally in doses of 0.5 mg and then 1 mg twice daily for 4 days each and 2 mg twice daily for the remainder of the trial. Patients on treatment with prazosin had an increased urinary flow rate as compared to placebo with a significant reduction in maximum voiding detrusor pressure and maximum detrusor pressure at peak urinary flow. Although a significant effect on frequency was not demonstrated, standard parameters of detrusor instability were reduced. Investigators' double-blind overall assessment of efficacy significantly favoured the prazosin treatment. Twelve patients were excluded from the final analysis, 8 being withdrawn because of adverse effects, 5 on treatment with prazosin and 3 in the placebo group. Oral prazosin appears to be safe and effective in the long-term treatment of patients with benign prostatic hyperplasia.


The Effect of Pre-Incision Field Block versus Post-Incision Inguinal Wound Infiltration on Postoperative Pain after Paediatric Herniotomy.
The Ilioinguinal/iliohypogastric nerve block has been shown to significantly decrease opioid analgesic requirements and side effects after inguinal herniotomy. We compared the effect of pre-incisional field block with 0.25% bupivacaine and post-incisional wound infiltration with 0.25% bupivacaine for postoperative pain control after inguinal herniotomy. This was a randomized controlled double blind study in 62 ASA I and II children aged 1-7 years scheduled for inguinal herniotomy. They were assigned to receive either pre-incision field block (group I) or post-incision wound infiltration at the time of wound closure (group II). The pain score was assessed in the recovery room using mCHEOPS score and VAS or FLACC score at home by the parents for 24 hours. The mean pain scores during the 2 hour stay in the recovery room, at 12 and 18 hours at home were similar in both groups, p > 0.05. However, the mean pain scores were significantly lower at 6 hours at home in group I (1.22 ± 0.57) than in group II (1.58 ±0.90), p <0.001, but significantly higher at 24 hours at home in group I (3.29 ± 0.46) than in group II (2.32 ± 0.24), p = 0.040. There was no difference in mean paracetamol requirement, and in the number of patients who required paracetamol for pain relief at home in both groups, p > 0.05. We have demonstrated that both pre-incisional ilioinguinal/iliohypogastric field block and post incisional wound infiltration provided adequate postoperative analgesia for 24 hours after inguinal herniotomy.


Hiding effort to gain a competitive advantage: Evidence from China.
Previous studies with Western populations have shown that adolescents' tendency to downplay their academic effort is affected by two kinds of motives: ability-related motives (e.g., to appear competent) and social approval motives (e.g., to be popular). In this research, we test for the presence of additional competition-related motives in China, a culture placing strong emphasis on academic competition. Study 1 (N = 150) showed that, in response to a scenario in which a hard-working high-school junior hid effort from classmates, the most highly endorsed explanation was "to influence others to work less hard to maintain a competitive advantage." Study 2 (N = 174) revealed that competition-related explanations were endorsed relatively more often when the speaker and audience had similar academic rankings. This tendency was most evident when both speaker and audience were top performers, and when this was the case, participants' desire to demonstrate superiority over others was a positive predictor of endorsement of competition-related motives. Study 3 (N = 137) verified that competition-related motives were more strongly endorsed among Chinese participants than U.S. These results suggest that at least in cultures that emphasize academic competition and in contexts where competition is salient, hiding effort is often about attempting to gain strategic advantage.


Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats.
Little information is available on proteolytic pathways responsible for muscle wasting in cancer cachexia. Experiments were carried out in young rats to demonstrate whether a small (< 0.3% body weight) tumor may activate the lysosomal, Ca(2+)-dependent, and/or ATP-ubiquitin-dependent proteolytic pathway(s) in skeletal muscle. Five days after tumor implantation, protein mass of extensor digitorum longus and tibialis anterior muscles close to a Yoshida sarcoma was significantly reduced compared to the contralateral muscles. According to in vitro measurements, protein loss totally resulted from increased proteolysis and not from depressed protein synthesis. Inhibitors of lysosomal and Ca(2+)-dependent proteases did not attenuate increased rates of proteolysis in the atrophying extensor digitorum longus. Accordingly, cathepsin B and B+L activities, and mRNA levels for cathepsin B were unchanged. By contrast, ATP depletion almost totally suppressed the increased protein breakdown. Furthermore, mRNA levels for ubiquitin, 14 kDa ubiquitin carrier protein E2, and the C8 or C9 proteasome subunits increased in the atrophying muscles. Similar adaptations occurred in the muscles from cachectic animals 12 days after tumor implantation. These data strongly suggest that the activation of the ATP-ubiquitin-dependent proteolytic pathway is mainly responsible for muscle atrophy in Yoshida sarcoma-bearing rats.


Confirmatory factor analysis of 20-item toronto alexithymia scale in spanish patients with substance use disorder.
Alexithymia is highly prevalent in patients with substance use disorders (SUDs) and has been implied in SUD pathogenesis and treatment outcomes. However, the psychometric properties of the most-used instrument for evaluating alexithymia (the 20-item Toronto Alexithymia Scale, TAS-20) have been scarcely studied in relation to SUD patients.


Adipocyte fatty acid-binding protein exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier.
Adipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood-brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects. Circulating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9. A-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.


Effectiveness of Early Advanced Glycation End Product Accumulation Testing in the Diagnosis of Diabetes: A Health Risk Factor Analysis Using the Body Mass Index as a Moderator.
To evaluate the value of non-invasive detection of advanced glycation end products (AGEs) in the early screening of type 2 diabetes mellitus (T2DM) in the community of China. From January 2018 to January 2019, a total of 912 patients with community health physical examination and no history of T2DM were selected, excluding the results of missing value > 5%. Finally, 906 samples were included in the study, with a response rate of 99.3%. Non-invasive diabetic detection technology was used to detect AGEs in the upper arm skin of all participants, AGE accumulations were classified as ≤P25, P25∼P50, P50∼P75, and >P75; HbA1c, insulin, C-peptide, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), creatinine, urea, and other indicators were measured at the same time. Univariate analysis of variance was used to compare the differences in general data, biochemical indexes, skin AGE levels, and blood glucose among groups, and logistic regression analysis and latent category analysis were performed. In univariate analysis, SBP, FBG, HbA1c, and age were correlated with higher AGE (p < 0.01); TG, TC, HDL, UA, and gender were not positively correlated with AGE (p < 0.01). After controlling for covariates (waist circumference, hip circumference), AGE accumulation was interacted with other variables. The results of latent category analysis (LCA) showed that the health risk factors (HRFs), including age, systolic blood pressure, HbA1c, FBG, triglyceride, total cholesterol, HDL-C, and uric acid, were divided as three groups, and AGE is divided into four categories according to the quartile method, which were low risk (≤P25), low to medium risk (P25∼P50), medium to high (P50∼P75), and high risk (>P75), respectively. The association between the quartile AGE and risk factors of the OR values was 1.09 (95% CI: 1.42, 2.86), 2.61 (95% CI: 1.11, 6.14), and 5.41 (95% CI: 2.42, 12.07), respectively. The moderation analysis using the PROCESS program was used to analyze whether BMI moderated the link between risk factors and AGE accumulation. There was also a significant three-way interaction among HRFs, BMI, and gender for AGE accumulation in the total sample (β = -0.30). Non-invasive skin detection of AGEs has a certain application value for the assessment of T2DM risk and is related to a variety of risk factors.


Pituitary enlargement, pituitary failure, and primary hypothyroidism.
Enlargement of the pituitary gland associated with primary hypothyroidism was observed in two patients. Serum thyroid-stimulating hormone (TSH) concentration and the TSH response to thyrotropin-releasing hormone were increased in both. Other pituitary function tests were subnormal in both patients, suggesting that a thyrotroph pituitary tumor was present that compromised the other pituicytes. The presence of a pituitary tumor secondary to primary hypothyroidism and resulting pituitary failure should be considered in all patients with long-standing primary hypothyroidism.


2-Acetylpyridine thiosemicarbazones. 8. Derivatives of 1-acetylisoquinoline as potential antimalarial agents.
A series of 1-acetylisoquinoline thiosemicarbazones was prepared in order to evaluate their antimalarial properties. This was achieved by the reaction of 1-acetylisoquinoline with methyl hydrazinecarbodithioate to give methyl 3-[1-(1-isoquinolinyl)ethylidene]hydrazinecarbodithioate (II). Displacement of the S-methyl group from this intermediate by various primary and secondary amines afforded the desired 1-acetylisoquinoline thiosemicarbazones (III). Thiosemicarbazides in which the azomethine moiety of the latter was reduced could be prepared by the reaction of II with NaBH4 to give methyl 3-[1-(1-isoquinolinyl)ethyl]hydrazinecarbodithioate (VIII). Reaction of VII with the appropriate amine gave 1-[1-(1-isoquinolinyl)ethyl]thiosemicarbazides (IX). Evaluation of the antimalarial activity of series III and IX in mice infected with Plasmodium berghei indicated that cures were attainable at dose levels of 40-160 mg/kg.


Association of omega-6 polyunsaturated fatty acids with blood pressure: A systematic review and meta-analysis of observational studies.
This systematic review and meta-analysis aimed at summarizing earlier findings on the association of n-6 PUFAs levels in diets or blood with blood pressure. PubMed/Medline, Scopus, and Web of Science were searched for observational studies. Publications with data on the risk of hypertension, or the correlation between n-6 PUFAs or mean values of serum n-6 PUFAs levels in normotensive and hypertensive were included. Twenty-two studies (16 cross-sectional studies, 5 cohorts and one case-control) were eligible. Combining 14 extracted effect sizes showed that higher circulatory/dietary n-6 PUFAs tended to be associated with 10% lower risk of HTN (95% CI: 0.81, 1.00), whereas combining 23 effect sizes illustrated no difference in circulatory/dietary n-6 PUFAs mean levels between normotensive and hypertensive subjects. According to subgroup analysis based on fatty acid types, total n-6 PUFAs (OR = 0.82, 95% CI: 0.70, 0.97) and linoleic acid (OR = 0.56, 95% CI: 0.39, 0.82) were inversely related to the risk of HTN. Circulatory/dietary n-6 PUFAs were correlated neither with systolic nor with diastolic blood pressure. Higher circulatory/dietary n-6 PUFAs tend to be associated with lower odds of HTN. Particularly, total n-6 PUFAs and linoleic acid were associated with lower risk of HTN.


Theory of competitive counterion adsorption on flexible polyelectrolytes: divalent salts.
The counterion distribution around an isolated flexible polyelectrolyte in the presence of a divalent salt is evaluated using the adsorption model [M. Muthukumar, J. Chem. Phys. 120, 9343 (2004)] that considers the Bjerrum length, salt concentration, and local dielectric heterogeneity as physical variables in the system. Self-consistent calculations of effective charge and size of the polymer show that divalent counterions replace condensed monovalent counterions in competitive adsorption. The theory further predicts that at modest physical conditions for a flexible polyelectrolytes such as sodium polystyrene sulfonate in aqueous solutions polymer charge is compensated and reversed with increasing divalent salt. Consequently, the polyelectrolyte shrinks and reswells. Lower temperatures and higher degrees of dielectric heterogeneity between chain backbone and solvent enhance condensation of all species of ions. Complete diagrams of states for the effective charge calculated as functions of the Coulomb strength and salt concentration suggest that (a) overcharging requires a minimum Coulomb strength and (b) progressively higher presence of salt recharges the polymer due to either electrostatic screening (for low Coulomb strengths) or coion condensation (for high Coulomb strengths). Consideration of ion-bridging by divalent counterions leads to a first-order collapse of polyelectrolytes in modest presence of divalent salts and at higher Coulomb strengths. The authors' theoretical predictions are in agreement with the generic results from experiments and simulations.


Soluplus-coated colloidal silica nanomatrix system for enhanced supersaturation and oral absorption of poorly water-soluble drugs.
In this study, a Soluplus-coated colloidal silica nanomatrix (SCCSN) formulation for the entrapment of poorly water-soluble drugs was devised. The maximum supersaturation of the drug-loaded nanomatrix was higher than that of a physical mixture as indicated by the results of in vitro kinetic solubility studies. For atorvastatin calcium, dutasteride, and sorafenib tosylate, there were 2.8-, 326-, and 46.4-fold increases in solubility, respectively. For dutasteride, a promising 4.7-fold increase for in vivo oral drug absorption in the entrapped nanomatrix was observed as compared to the free physical mixture, supported by statistical significance testing of pharmacokinetic parameters.


Intensity-modulated radiotherapy for nasopharyngeal carcinoma: the reduction of radiation-induced trismus.
The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last follow-up. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT.


Application of immunohistochemistry in breast pathology: a review and update.
Immunohistochemistry is a valuable tool in routine breast pathology, used for both diagnostic and prognostic parameters. The diagnostic immunomarkers are the scope of this review. Most breast lesions can be diagnosed on routine hematoxylin-eosin sections; however, in several scenarios, such as morphologically equivocal cases or metastatic tumors of unknown primary, the appropriate application of immunohistochemistry adds true value in reaching an accurate diagnosis. To evaluate the diagnostic utility of the most commonly studied immunomarkers in the field of breast pathology by review of the literature, using the database of indexed articles in PubMed (US National Library of Medicine, Bethesda, Maryland) from 1976 to 2013. Literature review, and author's research data and personal practice experience. The appropriate use of immunohistochemistry by applying a panel of immunomarkers and using a standardized technical and interpretational method will complement the morphologic assessment and aid in the accurate classification of difficult breast lesions and the identification of metastasis from a breast primary.


Effects of oral carbonic adsorbent (AST-120) on kidney of early-stage chronic kidney disease rats.
To investigate the therapeutic effects of oral carbonic adsorbent on rats with early-stage renal failure. The early-stage renal failure model was established with three-fourth subtotal nephrectomy Wistar rats. Four weeks after the subtotal nephrectomy, the rats were randomly divided into four groups: (1) adsorbent diet (AD) rats; (2) low protein diet (LPD) group; (3) low protein and AD rats; and (4) normal diet rats as control (ctrl) group. Sham operation group is set as well. The therapeutic effects of adsorbent were examined after 15 weeks treatment. The level of 24 hours urinary protein excretion, serum creatinine (Scr), index of glomerulosclerosis (GSI) and tubulointerstitial fibrosis score (TIFS) of rats with adsorbent or LPD treatment are significantly lower than ctrl group rats. The combination of adsorbent and LPD lowered level of 24 hours urinary protein excretion, Scr, index of GSI and TIFS compared with LPD or adsorbent treatment alone. Both AST-120 and LPD treatment lowered the Scr and blood urea nitrogen level as well as ameliorated the proteinuria and glomerular and tubulointerstitial damage of rats with early stage renal failure. The combined treatment of oral carbonic adsorbent and LPD showed greater therapeutic effects.


Interval MULTIMOORA Method Integrating Interval Borda Rule and Interval Best-Worst-Method-Based Weighting Model: Case Study on Hybrid Vehicle Engine Selection.
In this paper, we present an interval MULTIMOORA method with complete interval computation in which the interval distances of interval numbers and preference matrix are used. In addition, we propose a group interval best-worst method (BWM) with interval preference degree. The group interval BWM has a hierarchical structure of group decision making with two levels of experts. Beside employing the dominance theory to integrate subordinate rankings, we introduce the interval Borda rule as an aggregation function which does not have the defects of the dominance theory. We calculate the objective interval weights of criteria based on the interval entropy method, which are integrated by the subjective weights computed by the group interval BWM. The approach presented in this paper is verified by a real-world engineering selection problem of a hybrid vehicle engine based on real data and opinions of engineering design experts of the automotive industry of Iran. The preference-based and dominance-based ranking lists are presented for the problem. We solve the same case by employing the interval TOPSIS and VIKOR methods. Eventually, all resultant rankings are compared based on Spearman rank correlation coefficients.


A microdosimetry study for a realistic shaped nucleus.
In the last decades, the effects of ultrashort pulsed electric fields have been investigated demonstrating their capability to be involved in a great number of medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). In particular, experiments in literature demonstrate that internal structures can be involved when pulse duration is reduced. Up to now, the mechanism that permits the electroporation phenomenon has not been completely understood and hence atomistic, microdosimetry and dosimetry models have been developed to help in this field. Aim of this work is to demonstrate the importance of realistically model also the internal organelles to obtain predictive results of effects at sub-cellular level with a microdosimetry model.


Development of Personalized Molecular Therapy for Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is characterized by extensive clinical and biological heterogeneity. Despite vast advances in understanding the molecular pathology in AML during the last two decades few new AML therapeutics have been approved by the European Medicines Agency. Since 2005 only the epigenetic modulators decitabine and azacytidine, as well as histamine (plus interleukin- 2) have been approved against AML. None of these have outstanding efficiency, and decitabine and azacytdine have only been incorporated in frontline therapy of AML with limited enthusiasm. The majority of AML patients are frail and elderly, and lack of mild but effective agents for this patient cohort constitutes a major unmet need as overall survival remains poor. Along with the recent advancements in the molecular characterization of AML, numerous targeted therapies have been tested in clinical trials. In this review, we discuss the biological rationale for a selection of these novel therapeutic approaches, including epigenetic modifiers, agents targeting signalling pathways and inhibitors of nuclear-cytoplasmic shuttling. Further we discuss some of the possible shortcomings in current trial design that could explain the apparent incoherence between our improved biological knowledge and the lack of progress in therapy development of AML.


Prenatal diagnosis of skeletal dysplasias using whole exome sequencing in China.
Skeletal dysplasias account for nearly 10% of fetal structural malformations detected by ultrasonography. This clinically heterogeneous group of genetic anomaly includes at least 461 genetic skeletal disorders with extreme clinical, phenotypic, and genetic heterogeneities, thus, significantly complicates accurate diagnosis. Researches have used whole exome sequencing (WES) for prenatal molecular diagnoses of skeletal dysplasias, however, data are still limited. DNA extracted from umbilical cord blood or amniocytes from fetuses suspected of skeletal dysplasias based on ultrasound evaluations were analyzed by WES. Blood samples were taken from the parents of the positive fetuses for co-segregation analysis using Sanger sequencing. Definitive molecular diagnosis was made in 6/8 (75%) cases, comprised of 5 de novo disease-causing changes in 3 genes (FGFR3, COL2A1, and COL1A2) and one proband with a biallelic deficiency for Lamin B Receptor(LBR),and including 3 novel variants. All fetuses had no detectable copy number variation (CNV) from sequencing results. Our study suggests that WES is an efficient approach for prenatal diagnosis of fetuses suspected of skeletal abnormalities and contributes to parental genetics counseling and pregnancy management.


Effects of the manual laryngeal musculoskeletal tension reduction technique as a treatment for functional voice disorders: perceptual and acoustic measures.
During a 2-year period, 17 patients with "functional dysphonia" were assessed and managed in a hospital setting. A single treatment approach, known as manual laryngeal musculoskeletal tension reduction, was employed. The effects of the therapy regimen were analyzed using perceptual and acoustical measures of vocal function. The results indicated a significant change in the direction of "normal" vocal function in the majority of patients within one treatment session. Perceptual measures of severity were consistently more likely to be rated as normal following treatment. Acoustic measures of voice confirmed significant improvements in jitter, shimmer, and signal-to-noise ratio (SNR). Results are discussed in terms of the clinical utility and effectiveness of this treatment approach for functional dysphonia.


Eriocalyxin B alleviated ischemic cerebral injury via limiting microglia-mediated excessive neuroinflammation in mice.
Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease by suppressing the microglial overactivation. This study aims to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced by intraluminal filament method in internal carotidartery of mice, which underwent an immediately intraperitoneal injection of EriB (10 mg/kg) post surgery. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA and immunoblotting revealed that EriB administration reduced brain infarct and neuron death, ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, expression of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusions, EriB exerted anti-inflammatory effects in ischemia stroke through regulating NF-κB signaling pathway, which may provide insights into the neuroprotective effect of EriB on the treatment of ischemic stroke.


Comparative study to predict toxic modes of action of phenols from molecular structures.
Quantitative structure-activity relationship models for the prediction of mode of toxic action (MOA) of 221 phenols to the ciliated protozoan Tetrahymena pyriformis using atom-based quadratic indices are reported. The phenols represent a variety of MOAs including polar narcotics, weak acid respiratory uncouplers, pro-electrophiles and soft electrophiles. Linear discriminant analysis (LDA), and four machine learning techniques (ML), namely k-nearest neighbours (k-NN), support vector machine (SVM), classification trees (CTs) and artificial neural networks (ANNs), have been used to develop several models with higher accuracies and predictive capabilities for distinguishing between four MOAs. Most of them showed global accuracy of over 90%, and false alarm rate values were below 2.9% for the training set. Cross-validation, complementary subsets and external test set were performed, with good behaviour in all cases. Our models compare favourably with other previously published models, and in general the models obtained with ML techniques show better results than those developed with linear techniques. We developed unsupervised and supervised consensus, and these results were better than our ML models, the results of rule-based approach and other ensemble models previously published. This investigation highlights the merits of ML-based techniques as an alternative to other more traditional methods for modelling MOA.


[The therapeutic and recreational potential of the «Goryachy Plyazh» physiotherapeutic facility on the Kunashir island].
The ever increasing attention to the further development of the health resort business and touristic activities in this country implies the necessity of the proper scientifically sound substantiation for the more efficient exploitation of the available spa and health resort resources of the Russian Far East as well as the ample recreational potential of this region taking into consideration that they have not been completely utilized during the preceding period. The objective of the present study was to evaluate the of the «Goryachy Plyazh (Hot Beach)» physiotherapeutic facility on the Kunashir island. We have studies the chemical, bacteriological, and radiological properties of thermal waters from the natural sources located in the vicinity of the «Goryachy Plyazh» physiotherapeutic facility. The medical potential of the area was assessed in accordance with the methodological guidelines №96/226 on drawing up the bioclimatic passport approved by the Ministry of Public Health of the Russian Federation on the 7thFebruary of 1997. We have proposed the aggregate indicator of the therapeutic and recreational potential making it possible to evaluate the totality of health-improving properties in the combination with the landscape and climatic characteristics of the locality of interest. The neighbourhood of the «Goryachy Plyazh» physiotherapeutic facility on the Kunashir island was found to harbour the sources of mineral waters of various types. Specifically, siliceous thermal waters of varying ionic composition (e.g. containing chlorides, sodium, silicium, and boron) of the Omsk and Ursdon types are suitable for multipurpose therapeutic utilization including the protracted internal application for the treatment of chronic gastritis and other intestinal problems, diseases of liver and endocrine system, as well as metabolic disorders. Mineral water of the Kul'dursky type can be used for the external use in the form of bathing and other hydrotherapeutic procedures for the management and prevention of the diseases of various dermatoses, the diseases of the nervous, musculoskeletal, and genitourinary systems. The results of the study give evidence of the ample aggregate therapeutic and recreational potential of the localities in the neighbourhood of the «Goryachy Plyazh» physiotherapeutic facility located on the Kunashir island amounting to 76.5% which suggests the very promising prospects for the further development and utilization of this territory for the health resort business and touristic activities.


"Alcohol is something that been with us like a common cold": community perceptions of American Indian drinking.
This study examined tribal members' perspectives on alcohol, risk factors, consequences, and community responses. Focus groups were conducted with five American Indian tribes between 1997 and 2001. Participants were knowledgeable of the cultural lives of their reservation communities. Although there was agreement regarding the pervasiveness of heavy drinking, participants reported different opinions about the meaning of alcohol and appropriate intervention strategies. Three dilemmas were identified, suggesting that community ambivalence may serve as a barrier to reducing problem drinking. Implications, limitations, and future research directions are discussed. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.


Kinetic properties of Qbeta replicase, an RNA dependent RNA polymerase.
The kinetic properties of Qbeta replicase, an RNA-dependent RNA polymerase, were investigated experimentally. The reaction at the A-incorporation site was inhibited by UTP and CTP with inhibition constants of 3.2 and 2.7 mM, respectively, while the reactions at the U-, G-, and C-incorporation sites were inhibited by ATP with inhibition constants of 1.09, 1.25, and 1.48 mM, respectively. When nucleotide concentrations were low, C was incorporated at the fastest rate and G at the slowest. Accordingly, the G-incorporation step largely limits the overall reaction rate. From the obtained kinetic parameters, calculations showed that the optimum ratio of the concentrations of the four nucleotides could be achieved by increasing the ratio of GTP concentration with a concomitant decrease in the ratios of CTP and ATP concentrations. Consequently, a 60 to 140% increase in the reaction rate is expected as compared to the rate with equimolar ratio of the four nucleotides.


Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen.
Collagen VII is the major structural component of the anchoring fibrils at the dermal-epidermal junction in the skin. It is secreted by keratinocytes as a precursor, procollagen VII, and processed into mature collagen during polymerization of the anchoring fibrils. We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA/DTAG within the NC-2 domain. Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro. Immunohistochemical and genetic evidence supported the involvement of these enzymes in cleaving type VII procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in cultured cutaneous cells. A naturally occurring deletion in the human COL7A1 gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII, and in mutant skin procollagen VII accumulated at the dermal-epidermal junction. On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did not prevent processing of procollagen VII to mature collagen, suggesting that mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen VII in situ.


Pharmacokinetics of ciprofloxacin in healthy Mexican volunteers.
Ciprofloxacin (CAS 85721-33-1) is a gyrase inhibitor used against a wide number of bacteria which develops a very low bacterial resistance. Its pharmacokinetics has been extensively studied using two main methods, liquid chromatography and microbiological assay. The pharmacokinetics of ciprofloxacin administered orally was evaluated in healthy Mexican volunteers after a dose of 500 mg. Ciprofloxacin was assayed from plasma by a specific HPLC method reading absorbance at 280 nm. Pharmacokinetic parameters were similar to reported values, including a previous study on Mexican healthy volunteers with the microbiological assay. AUC was 12.11 mg h/l, Cmax 2.44 mg/l, tmax 0.79 h and half-life 3.8 h. tmax was slightly shorter than those in other studies. Ciprofloxacin presented no adverse reactions and can be dosed to people with Amerindian origin in the same dose regimes as prescribed to Caucasians in order to achieve minimal inhibitory concentrations against a wide range of microbial pathogens.


Increases in synthetic cannabinoids-related harms: Results from a longitudinal web-based content analysis.
Synthetic Cannabinoid Receptor Agonists (SCRA), also known as "K2" or "Spice," have drawn considerable attention due to their potential of abuse and harmful consequences. More research is needed to understand user experiences of SCRA-related effects. We use semi-automated information processing techniques through eDrugTrends platform to examine SCRA-related effects and their variations through a longitudinal content analysis of web-forum data. English language posts from three drug-focused web-forums were extracted and analyzed between January 1st 2008 and September 30th 2015. Search terms are based on the Drug Use Ontology (DAO) created for this study (189 SCRA-related and 501 effect-related terms). EDrugTrends NLP-based text processing tools were used to extract posts mentioning SCRA and their effects. Generalized linear regression was used to fit restricted cubic spline functions of time to test whether the proportion of drug-related posts that mention SCRA (and no other drug) and the proportion of these "SCRA-only" posts that mention SCRA effects have changed over time, with an adjustment for multiple testing. 19,052 SCRA-related posts (Bluelight (n=2782), Forum A (n=3882), and Forum B (n=12,388)) posted by 2543 international users were extracted. The most frequently mentioned effects were "getting high" (44.0%), "hallucinations" (10.8%), and "anxiety" (10.2%). The frequency of SCRA-only posts declined steadily over the study period. The proportions of SCRA-only posts mentioning positive effects (e.g., "High" and "Euphoria") steadily decreased, while the proportions of SCRA-only posts mentioning negative effects (e.g., "Anxiety," 'Nausea," "Overdose") increased over the same period. This study's findings indicate that the proportion of negative effects mentioned in web forum posts and linked to SCRA has increased over time, suggesting that recent generations of SCRA generate more harms. This is also one of the first studies to conduct automated content analysis of web forum data related to illicit drug use.


The role of RuvA octamerization for RuvAB function in vitro and in vivo.
RuvA plays an essential role in branch migration of the Holliday junction by RuvAB as part of the RuvABC pathway for processing Holliday junctions in Escherichia coli. Two types of RuvA-Holliday junction complexes have been characterized: 1) complex I containing a single RuvA tetramer and 2) complex II in which the junction is sandwiched between two RuvA tetramers. The functional differences between the two forms are still not clear. To investigate the role of RuvA octamerization, we introduced three amino acid substitutions designed to disrupt the E. coli RuvA tetramer-tetramer interface as identified by structural studies. The mutant RuvA was tetrameric and interacted with both RuvB and junction DNA but, as predicted, formed complex I only at protein concentrations up to 500 nm. We present biochemical and surface plasmon resonance evidence for functional and physical interactions of the mutant RuvA with RuvB and RuvC on synthetic junctions. The mutant RuvA with RuvB showed DNA helicase activity and could support branch migration of synthetic four-way and three-way junctions. However, junction binding and the efficiency of branch migration of four-way junctions were affected. The activity of the RuvA mutant was consistent with a RuvAB complex driven by one RuvB hexamer only and lead us to propose that one RuvA tetramer can only support the activity of one RuvB hexamer. Significantly, the mutant failed to complement the UV sensitivity of E. coli DeltaruvA cells. These results indicate strongly that RuvA octamerization is essential for the full biological activity of RuvABC.


Hot off the press.
A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as vlasoulamine A from Vladimiria souliei.


Cloning and expression of a soluble sialidase from Chinese hamster ovary cells: sequence alignment similarities to bacterial sialidases.
A cDNA encoding a soluble sialidase from Chinese hamster ovary (CHO) cells has been cloned and expressed. Completely degenerate oligonucleotide primers, which were based on the amino acid sequence of peptides obtained from the purified sialidase (Warner et al., Glycobiology, 3, 455-463, 1993), and the polymerase chain reaction, with single-stranded cDNA template, were employed to generate a unique oligonucleotide probe. The unique probe of 93 bp was used for screening a lambda gt 10 CHO cell cDNA library. A single clone, which contained a 1.4 kb insert, was isolated after screening 450,000 recombinants. The complete coding region of the protein, 1137 nucleotides, was contained in the isolated clone and it predicted a protein of 379 amino acids. The insert had a 186 bp 5' non-coding leader sequence and a 40 bp 3' non-coding region. No signal peptide was identified in the insert, suggesting a cytosolic localization for the protein. No significant primary sequence identities were observed when the deduced amino acid sequence of the CHO cell sialidase was compared with other mammalian proteins or microbial sialidases. However, the protein had significant sequence alignment similarity with several bacterial sialidases. Two 'Asp box' motifs in the CHO cell sialidase had a remarkable alignment positioning in the protein sequence with the similar motifs of the Salmonella LT2 and Clostridium perfringens sialidases. High levels of the enzyme were expressed in Spodoptera frugiperda cells infected with a modified Autographa californica nuclear polyhedrosis virus harbouring the sialidase cDNA.


Determination of Hepatic Iron Deposition in Drug-Induced Liver Fibrosis in Rats by Confocal Micro-XRF Spectrometry.
Liver fibrosis is the intermediate process and inevitable stage of the development of chronic liver disease into cirrhosis. Reducing the degree of liver fibrosis plays an extremely important role in treating chronic liver disease and preventing liver cirrhosis and liver cancer. The formation of liver fibrosis is affected by iron deposition to a certain extent, and excessive iron deposition further induces liver cirrhosis and liver cancer. Herein, confocal microbeam X-ray fluorescence (μ-XRF) was used to determine the intensity and biodistribution of iron deposition at different time points in the process of liver fibrosis induced by thioacetamide (TAA) in rats. To our best knowledge, this is the first study using confocal μ-XRF to analyze hepatic iron deposition in hepatic fibrosis. The results showed that there are minor and trace elements such as iron, potassium, and zinc in the liver of rats. Continuous injection of TAA solution resulted in increasing liver iron deposition over time. The intensity of iron deposition in liver tissue was also significantly reduced after bone mesenchymal stem cells (BMSCs) were injected. These findings indicated that confocal μ-XRF can be used as a nondestructive and quantitative method of evaluating hepatic iron deposition in hepatic fibrosis, and iron deposition may play an important role in the progression of hepatic fibrosis induced by TAA.


Evaluation of emergency medicine residents competencies in electrocardiogram interpretation.
An electrocardiogram (ECG) leads physicians to diagnose many potentially life-threatening cardiac, metabolic, electrolyte, and toxicological conditions. This study was designed to evaluate the competency of emergency medicine residents (EMRs) in comparison with cardiologists in the interpretation of ECG when an interpretation checklist is used. This clinical trial was done in the emergency wards of the first grand general hospital of Iran. Patients were categorized in three classes of disorder severity based on ECG abnormalities. The two stages of the study included the survey phase (Stage I), training phase and intervention phase (Stage II). Accuracy of ECG interpretation by EMRs and cardiologists was compared before and after using a Daily ECG Check List (DECKList). One hundred and fifty ECGs were evaluated in Stage I, before DECKList usage, and 150 ECGs were evaluated in stage II, after DECKList usage by EMRs. Mean age of participants was 60.13 years in Stage I and 61.66 years in Stage II. Stage I and II were similar to each other in terms of disorder severity (P=0.22). Mean the ECG interpretation score was significantly different between Stages I and II (P<0.001). Concordance of ECG diagnosis between EMRs and cardiologists was significantly different in Stages I and II (P<0.01). In first-year EMRs, ECG diagnosis scores in stages I and II were not changed significantly. However, ECG interpretation scores increased significantly in first-year EMRs (P=0.04). In second-year EMRs, both ECG interpretation and ECG diagnosis scores improved significantly (P<0.05 and P<0.01, respectively). In third year EMRs, ECG interpretation was not improved but ECG diagnosis based on two methods improved significantly (P<0.05). The significant increase in accuracy of ECG interpretation and final diagnosis can be attributed to the utilization of a checklist by EMRs especially in the first year and second residents.


99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment.
In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.


Hypoxia-induced cell death of HepG2 cells involves a necrotic cell death mediated by calpain.
To elucidate mechanism of cell death in response to hypoxia, we attempted to compare hypoxia-induced cell death of HepG2 cells with cisplatin-induced cell death, which has been well characterized as a typical apoptosis. Cell death induced by hypoxia turned out to be different from cisplatin-mediated apoptosis in cell viability and cleavage patterns of caspases. Hypoxia-induced cell death was not associated with the activation of p53 while cisplatin-induced apoptosis is p53 dependent. In order to explain these differences, we tested involvement of micro-calpain and m-calpain in hypoxia-induced cell death. Calpains, especially micro-calpain, were initially cleaved by hypoxia, but not by cisplatin. Interestingly, the treatment of a calpain inhibitor restored PARP cleavage that was absent during hypoxia, indicating the recovery of activated caspase-3. The inhibition of calpains prevented proteolysis induced by hypoxia. In addition, hypoxia resulted in a necrosis-like morphology while cisplatin induced an apoptotic morphology. The calpain inhibitor prevented necrotic morphology induced by hypoxia and converted partially to apoptotic morphology with nuclear segmentation. Our result suggests that calpains are involved in hypoxia-induced cell death that is likely to be necrotic in nature and the inhibition of calpain switches hypoxia-induced cell death to apoptotic cell death without affecting cell viability.


Lessons from the major studies in COPD: problems and pitfalls in translating research evidence into practice.
Translating the growing evidence base on COPD management into practice can be challenging and understanding the strengths and weakness of published studies is crucial. Studies should conform to the standards of CONSORT statement; they should be sufficiently powered, participants should be randomised, there should be assignment concealment, and the outcome measures and analyses should be decided in advance. The interpretation of the results may be affected by age and severity inclusion criteria for the study and the exclusion of patients with co-morbid illnesses. Whether previous medication is continued or stopped can affect the interpretation of the results. Secondary analyses in sub-groups should be viewed with caution unless pre-specified and accommodated in the trial design and power calculations. Real world observational studies may be confounded by non-randomisation of participants but can sometimes yield valuable insights. The way in which the results are presented can influence their interpretation and their magnitude with respect to minimal important differences as well as statistical significance is important. Research help formulate management algorithms but often the questions they address are too specific to allow evidence-based sequencing of therapies.


Better treatment of outpatients with type 1 diabetes after introduction of continuous subcutaneous insulin infusion.
Continuous subcutaneous insulin infusion (CSII) was introduced in the outpatient diabetes clinic in Fredericia, Denmark, in 2005. The aim of this study was to evaluate the quality of metabolic control and patient satisfaction in type 1 diabetic patients treated with CSII. In 2009-2010, a database with registration of metabolic variables and patient satisfaction was established. The collected material is a combination of retrospective and prospective data. Patient satisfaction was measured by use of the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and change (DTSQc) versions. By 31 December 2010, the database contained data from 68 active patients. Compared with before the initiation of CSII, glycohaemoglobin (HbA1c) had decreased significantly from 8.0% (5.8-13.7%) to 7.6% (6.1-9.5%). The improved glycaemic control was maintained each year until ≤ 4 years after initiation of CSII (p < 0.01).The fraction of patients with an HbA1c ≤ 7% had increased from 13% to 24%, the fraction of patients with an HbA1c > 9% had decreased from 18% to 3%, and the number of serious attacks of hypoglycaemia had decreased (p < 0.05). Only three episodes of ketoacidosis were observed. The DTSQs and DTSQc showed a higher patient satisfaction during CSII treatment (p < 0.01) than before its introduction. Compared with before the introduction of CSII, the patient satisfaction score had increased from 19 (12-33) to 34.5 (27-36) (p < 0.01). Type 1 diabetes patients who were changed from treatment with multi-injection therapy to CSII showed improved glycaemic control, a reduced number of hypoglycaemic attacks and improved and very high levels of patient satisfaction.


Formation and destruction of multilayered tori in coupled map systems.
The paper first illustrates how multilayered tori can arise through one or more pitchfork bifurcations of the saddle cycle on an ordinary resonance torus. The paper hereafter describes three different scenarios by which a multilayered torus can be destructed. One scenario involves a saddle-node bifurcation in which the middle layer of a three-layered torus disappears in an abrupt transition to chaos while the outer-layer manifolds and their associated saddle and unstable-focus cycles continue to exist and to control the transient dynamics. In a second scenario, the unstable focus cycles of the intermediate layers in a five-layered torus turn into unstable nodes, and closed loop connections are established between the unstable nodes and the points of the stable resonance node on the torus. Finally, a third scenario describes a transition in which homoclinic bifurcations destroy first the outer layers and thereafter also the inner layer. The paper also illustrates how the formation and destruction of multilayered tori can occur in the cluster dynamics of an ensemble of globally coupled maps. This leads to three additional scenarios for the destruction of multilayered tori.


Hydrophobically directed selective reduction of ketones.
Three hydrophobic borohydrides carrying phenyl, pentafluorophenyl, and beta-naphthyl groups were used to reduce ketones in water and in methanol. With ketones carrying phenyl, naphthyl, or biphenyl substituents, there was preferential reduction in methanol of competing acetyl groups, either intermolecular or intramolecular, but preferential reduction of the aryl ketones in water. In the most extreme case, there was a 40-fold selectivity reversal. Lithium borohydride showed no such change in selectivity and favored acetyl reduction in both solvents. Salt and cosolvent effects indicate that hydrophobic packing is involved in the reaction of hydrophobic reagents with the aryl ketones. Some special interaction of the pentafluorophenyl group with aryl rings was also detected.


Glutamate decarboxylase antibodies in non-diabetic pregnancy precedes insulin-dependent diabetes in the mother but not necessarily in the offspring.
We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children. Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers who delivered a child in the city of Malmö, Sweden. A total of 42 mothers were identified in 1988 who, 1-18 years after their pregnancies, had developed either insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus. First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8% ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%) had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third, in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42 mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may predict insulin-dependent diabetes in the mother but not necessarily in the offspring.


Effect of integrated education on nurses' knowledge of haemodialysis vascular access.
The success of haemodialysis depends on access to the circulation. Preservation of the access site should be a primary goal of patient care. Little research on nursing interventions related to vascular access exists. Access care varies from centre to centre and there are often no written protocols for guidance. The aim of the study was to determine the effect of integrated education on nurses' knowledge. The fundamental principles of vascular access should be used to help train future dialysis staff members in order to improve quality of care. We must continue to gain knowledge in this important area through nursing research and education. This research demonstrates that integrated education improves the knowledge of nurses working in a renal unit.


Inaccuracy of available surgical risk scores to predict outcomes after transcatheter aortic valve replacement.
Despite encouraging short-term and mid-term results, transcatheter aortic valve implantation (TAVI) interventions are still burdened from high rates of adverse events, stressing the need for accurate predictive risk instruments. We compared available surgical risk scores to describe unfavorable outcomes after TAVI. The Age, Creatinine, and Ejection fraction (ACEF) score, the logistic Euroscore, and the Society of Thoracic Surgeons Mortality score (STS) were appraised for their independent power of prediction and for their accuracy (C-index) to predict 30-day and medium-term mortality, according to the Valve Academic Research Consortium. Nine hundred and sixty-two patients were included. All the scores demonstrated a moderate positive correlation. The closest correlation was observed between the STS score and Euroscore. After logistic regression analysis, STS score and Logistic Euroscore provided independent prediction for short-term all-cause mortality [P = 0.02, odds ratio (OR) 1.1; 95% confidence interval (CI) 1.06-1.31 and P = 0.027, OR 1.03; 95% CI 1.01-1.405]. For in-hospital complications, only STS score performed significantly (P = 0.005, OR 1.05; 95% CI 1.01-1.06). ACEF, Euroscore, and STS score showed low accuracy for 30-day all-cause mortality (area under the curve 0.6, 0.44-0.75; vs. 0.53, 0.42-0.61; vs. 0.62, 0.52-0.71, respectively), whereas STS score performed better for in-hospital complications (0.59, 0.55-0.64). Moreover, after Cox-multivariate adjustments, only ACEF score was near to significance to predict all-cause mortality at mid-term (OR 1.7; 0.8-2.9; P = 0.058), showing the highest accuracy (0.63, 0.55-0.71). In TAVI patients, ACEF score, STS score and Logistic Euroscore provided only a moderate correlation and a low accuracy both for 30-day and medium-term outcomes. Dedicated scores are needed to properly tailor time and kind of approach.


AED discontinuation may not be dangerous in seizure-free patients.
The decision to continue or to stop anticonvulsant treatment in patients with prolonged seizure remission is still a matter of debate. There is no evidence that continued treatment guarantees permanent seizure freedom. Up to 50% of patients achieve terminal remission (i.e., off drugs). Almost one-half of patients with untreated epilepsy are seizure-free for more than 5 years and the number of those with continuing seizures tends to decrease over time. In contrast, a substantial fraction of patients on chronic treatment with antiepileptic drugs (AEDs) may be exposed to clinically relevant adverse effects. Other disadvantages of continuing treatment indefinitely include the teratogenic risk, drug interactions, and the concern that AEDs may be unnecessary. The probability of remaining seizure-free after treatment discontinuation is about 70% at 2 years. Although different combinations of factors are thought to affect the risk of relapse, the prediction of individual outcome before withdrawal remains uncertain. As a consequence, the decision to withdraw or withhold treatment must be still individualized. In any patient, the decision to discontinue treatment should also take into account social aspects like driving license, job and leisure activities as well as emotional and personal factors and adverse effects or drug interactions. Patients will ultimately have to decide themselves whether they wish to discontinue drug treatment.


[The significance of CA-50, SLX and ST-439 in lung cancer].
Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).


[Orthopaedic relevance of baby carrying].
Recently, various ways of carrying a baby have become popular again. Different methods and options of infant carrying are largely influenced by current fashion trends. The term of baby carrying refers to carrying the infant close to the caregiver's body with special devices, which aid attachment parenting. The authors often face the question in the pediatric orthopedic clinic: what kind of carrying method to recommend to the parents. In this article the authors briefly present the different means of carrying devices and they review the literature regarding orthopedic consequences of baby carrying. For the healthy development of a child, position and correct support of the hips and the spine are essential, whereas the carrier's spinal protection is also an important aspect. After reviewing the literature, the authors conclude that baby carrying with an adequate device has advantages from orthopaedic point of view.


Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers.
Despite substantial survival benefits of risk-reducing mastectomy (RRM) and risk-reducing bilateral salpingo-oophorectomy (RRBSO) among BRCA mutation carriers, only a minority elect to undergo these procedures. This study investigates factors that might influence decision making regarding prophylactic surgeries among women with BRCA mutations. Unaffected BRCA mutation carriers who were counseled at our center and either underwent prophylactic surgery or participated in a high-risk surveillance program at our institution from 1998 through 2010 were included in the study. Medical records were reviewed and data collected included age, family history, parity, mutation type, history of breast biopsy or cosmetic surgery, and uptake of prophylactic surgeries. Among 136 unaffected women with BRCA mutations, uptake of RRM was 42% and uptake of RRBSO was 52%. Family history of first- and second-degree relatives being deceased from breast cancer was predictive of uptake of RRM and of RRBSO (odds ratio [OR], 11.0; P = .005; and OR, 15.8; P = .023, respectively), and history of a mother lost to pelvic cancer was predictive of uptake of RRBSO (OR, 7.9; P = .001). Parity also predicted both RRM and RRBSO uptake (OR, 4.2; P = .001; and OR, 5.4; P = .003, respectively). Age at the time of genetic testing and history of breast biopsy or cosmetic surgery were not predictive of RRM uptake. Perceptions of cancer risk are heavily influenced by particular features of an individual's family history and may be motivators in preventive surgery more than actual cancer risk estimations themselves. Awareness of subtle factors beyond the statistical risk for cancers is relevant when counseling at-risk women.


Beyond capital? The challenge for sociology in Britain.
This article offers a 'local', British, reading of Piketty's landmark book, Capital in the Twenty-First Century, suggesting that the challenge it offers to sociological approaches to inequality is more fundamental than hitherto recognized. The variations in 'national trajectories' exposed by Piketty reveal Britain to be anomalous in terms of standard approaches to the path dependencies embedded in different welfare regimes. Using the recent work of Monica Prasad on 'settler capitalism' in the USA and the tax and debt-finance regime associated with it, the article suggests that colonialism and empire and its postwar unravelling has had deep consequences for British social stratification, albeit largely neglected by British sociologists. Finally, it points to the fact that the form of tax and debt-finance regime that has become reinforced in Britain is at the heart of recent radical reforms to higher education. These are the currently unexplicated conditions of our future practice as sociologists and, therefore, an obstacle to building a critical sociology on the foundations laid out by Piketty.


Carbohydrate metabolism in normal and diabetic rats following long-term oral trypsin inhibitor administration.
The effect of long-term oral trypsin inhibitor administration on blood glucose, plasma insulin, liver, and muscle glycogen and glucose utilization in vitro by peripheral tissues in normal and diabetic rats was studied. In normal rats the glycogen levels in liver and muscle were increased after 3 weeks of treatment. Glucose oxidation (14CO2-production) was augmented in muscle after 3 and 8 weeks and in liver after 3 weeks. An increased 14C-incorporation into glycogen from 14C-glucose and increased glycogen concentration after incubation were found in muscle after 3 weeks. In diabetic rats the basal blood glucose was decreased after 3 and 5 weeks of treatment, and the basal plasma insulin:blood glucose ratio increased after 5 weeks. The glycogen levels were increased after 3 and 5 weeks in liver. No effect on glucose oxidation (14CO2-production) in muscle was found. The 14C-incorporation into glycogen and the total glycogen content, however, was increased in muscle after both 3 and 5 weeks. Incubation of muscle tissue with serum from normal or diabetic rats treated with oral trypsin inhibitor for 3 and 5 weeks respectively had no apparent acute effects on the glucose metabolism. It is suggested that the observed action of oral trypsin inhibitors on glucose metabolism in peripheral tissues is mediated by one or more unknown gastrointestinal factor(s).


Hepatitis B virus reactivation in a primary central nervous system lymphoma patient following intrathecal rituximab treatment.
A 69-year-old woman with relapsed primary central nervous system (CNS) lymphoma was treated with intrathecal rituximab without a concomitant systemic steroid or other chemotherapeutic drugs. Her initial viral status was HBs Ag negative and anti-HBs Ab positive. After 12 weeks of the last intrathecal rituximab application, the levels of AST and ALT were 1,005 and 1,134 IU/l, respectively. The viral status was changed as follows: HBs Ag positive, anti-HBs Ab negative, anti-HBe Ag positive, and anti-HBe Ab negative. The titer of hepatitis B virus (HBV) DNA was 106,000 IU/ml. She was diagnosed with acute hepatitis due to HBV reactivation. To our knowledge, this is the first reported case of HBV reactivation occurring after intrathecal rituximab monotherapy, suggesting that monitoring of HBV markers should be considered during intrathecal rituximab treatment in primary CNS lymphoma patients who are HBs Ag positive or anti-HBs Ab positive.


[Urinary catheter biofilm infections].
Urinary tract infections, most of which are biofilm infections in catheterized patients, account for more than 40% of hospital infections. Bacterial colonization of the urinary tract and catheters causes not only infection but also other complications such as catheter blockage by bacterial encrustation, urolithiasis and pyelonephritis. About 50% of long-term catheterized patients face urinary flow obstruction due to catheter encrustation, but no measure is currently available to prevent it. Encrustation has been known either to result from metabolic dysfunction or to be of microbial origin, with urease positive bacterial species implicated most often. Infectious calculi account for about 15-20% of all cases of urolithiasis and are often associated with biofilm colonization of a long-term indwelling urinary catheter or urethral stent. The use of closed catheter systems is helpful in reducing such problems; nevertheless, such a system only delays the inevitable, with infections emerging a little later. Various coatings intended to prevent the bacterial adhesion to the surface of catheters and implants and thus also the emergence of biofilm infections, unfortunately, do not inhibit the microbial adhesion completely and permanently and the only reliable method for biofilm eradication remains the removal of the foreign body from the patient.


Total body scanning with strontium-85 in the diagnosis of metastatic bone disease.
To demonstrate skeletal metastases before radiographic changes were apparent, Sr(85) scans were carried out on 46 patients who complained of sketetal pain but whose radiographs were negative. Positive scans were obtained in 34 patients, 20 of whom were subsequently shown to have metastases; three did not have skeletal metastases a year or more later; the outcome is unknown in 11 patients. Twelve patients had negative scans: three ultimately developed metastases, six did not, and three were inconclusive. Autoradiographs demonstrated Sr(85) concentrations in areas of reactive osteogenesis.Although not specific for skeletal metastases, Sr(85) scans are most helpful in substantiating this diagnosis when radiographic changes are absent.


[Exploring AT(1) and AT(2) angiotensin II receptors in humans].
The physiological effects of angiotensin II (Ang II) are mediated through specific AT(1) and AT(2) receptors. Tissue distribution and affinity of these receptors have been explored in binding studies, reverse transcriptase-polymerase chain reaction and in situ hybridisation. Sequencing has also demonstrated gene polymorphisms for both AT(1) and AT(2) receptors. Numerous potent nonpeptide antagonists of angiotensin converting enzyme or of AT receptors have been developed, thus providing a precise analysis of the physiology of the renin-angiotensin system. AT(1) receptors are widely expressed throughout adult tissues, while AT(2) receptors are mainly expressed in the fetus. Receptor density on the cell surface is regulated by multiple hormonal, cytokine and metabolic factors, and is thus profoundly affected by various pathological conditions, especially in the myocardium, kidney and blood vessels. To date, the precise molecular basis for these modifications has not been fully explained, although it may rely in part upon AT receptor gene polymorphisms, which could thus constitute increased risk factors for cardiovascular disease. AT(1) and AT(2) receptor expression is therefore influenced by both age and environmental specifications and is likely to be increased by a diet rich in salt or cholesterol, thus justifying the use of Ang II receptor antagonists in morbidity-mortality studies in high-risk patients.


Construction and preservation of a stable and highly expressed recombinant Helicobacter pylori vacuolating cytotoxin A with apoptotic activity.
H. pylori is closely related to the occurrence and development of various digestive gastritis, peptic ulcer and mucosa-associated lymphoid tissue (MALT) lymphoma. H. pylori is also a class I carcinogen of gastric cancer. VacA is the only exocrine toxin of H. pylori, which plays a very important role in the pathogenesis of H. pylori. The production of VacA in natural circumstances is complex with heavy workload and low yield. Therefore, it is very important to obtain recombinant VacA protein which is stable and biologically active. This study therefore aims to explore the expression, purification and stable storage of VacA toxin of H. pylori in E.coli, and to provide experimental basis for further exploration of the role of VacA in H. pylori -induced inflammation of cancer. A 2502-bp fragment and VacA gene were identified. An 89.7-kDa VacA34-854 recombinant protein was expressed and purified from the recombinant engineering bacteria and was preserved stably in 50 mM acetic acid buffer (pH 2.9). The amount of the recombinant protein was larger in the inclusion bodies than in the supernatant. In addition, after a 24-h culture with VacA recombinant protein, GES-1 cells demonstrated evidence of apoptosis including early nuclear immobilization and clustering under inverted microscope and TEM. It was found that VacA recombinant protein induced apoptosis by TUNEL assay. A VacA recombinant protein that is stably and highly expressed and possesses pro-apoptotic activity is successfully constructed. The protein is stably preserved in 50 mM acetic acid buffer (pH 2.9).


Dabigatran for the prevention of thromboembolic complications in the elderly: a RE-LY-able alternative to warfarin?
On October 19, 2010, the Food and Drug Administration approved dabigatran (Pradaxa) for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). The use of warfarin sodium has been considered a mainstay therapy for the prevention of thromboembolic complications secondary to AF. Despite its efficacy among oral antithrombotic agents for the prevention of thromboembolic complications secondary to AF, only about 67% of candidates for warfarin receive appropriate antithrombotic therapy. Dosed twice daily, dabigatran offers recipients the ability to forego regular international normalized ratio coagulation monitoring as well as eliminating dietary restrictions (i.e., vitamin K) associated with warfarin therapy. In a 2011 guideline update, dabigatran has been recognized by the American College of Cardiology and the American Heart Association as a useful alternative to warfarin in patients with AF who are at risk for thromboembolic complications and who are without severe renal or hepatic impairment. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study is the only direct, prospective, comparative clinical trial of dabigatran versus warfarin to date that enrolled subjects for the purpose of examining the ability of dabigatran to prevent stroke and thromboembolic complications associated with nonvalvular AF. Currently, the published literature has not adequately defined which patient populations would be most suitable to treat with dabigatran. While dabigatran has a place in the therapeutic prevention stroke and systemic embolism associated with AF, careful consideration of the risks and benefits of therapy is recommended.