Structure-function relationship of lipoprotein lipase-mediated enhancement of very low density lipoprotein binding and catabolism by the low density lipoprotein receptor. Functional importance of a properly folded surface loop covering the catalytic center.
We examined the structure-function relationship of human lipoprotein lipase (hLPL) in its ability to enhance the binding and catabolism of very low density lipoproteins (VLDL) in COS cells. Untransfected COS cells did not bind to or catabolize normal VLDL. Expression of wild-type hLPL by transient transfection enhanced binding, uptake, and degradation of the VLDL (a property of LPL that we call bridge function). Heparin pretreatment and a monoclonal antibody ID7 that blocks LDL receptor-binding domain of apoE both inhibited binding, and apoE2/E2 VLDL from a Type III hyperlipidemic subject did not bind. However, LDL did not reduce 125I-VLDL binding to the hLPL-expressing cells, whereas rabbit beta-VLDL was an effective competitor. By contrast, LDL reduced uptake and degradation of 125I-VLDL to the same extent as excess unlabeled VLDL or beta-VLDL. These data suggest that binding occurs by direct interaction of VLDL with LPL but the subsequent catabolism of the VLDL is mediated by the LDL receptor. Mutant hLPLs that were catalytically inactive, S132A, S132D, as well as the partially active mutant, S251T, and S172G, gave normal enhancement of VLDL binding and catabolism, whereas the partially active mutant S172D had markedly impaired capacity for the process; thus, there is no correlation between bridge function and lipolytic activity. A naturally occurring genetic variant hLPL, S447-->Ter, has normal bridge function. The catalytic center of LPL is covered by a 21-amino acid loop that must be repositioned before a lipid substrate can gain access to the active site for catalysis. We studied three hLPL loop mutants (LPL-cH, an enzymatically active mutant with the loop replaced by a hepatic lipase loop; LPL-cP, an enzymatically inactive mutant with the loop replaced by a pancreatic lipase loop; and C216S/C239S, an enzymatically inactive mutant with the pair of Cys residues delimiting the loop substituted by Ser residues) and a control double Cys mutant, C418S/C438S. Two of the loop mutants (LPL-cH and LPL-cP) and the control double Cys mutant C418S/C438S gave normal enhancement of VLDL binding and catabolism, whereas the third loop mutant, C216S/C239S, was completely inactive. We conclude that although catalytic activity and the actual primary sequence of the loop of LPL are relatively unimportant (wild-type LPL loop and pancreatic lipase loops have little sequence similarity), the intact folding of the loop, flanked by disulfide bonds, must be maintained for LPL to express its bridge function.


A method for measuring post-extraction alveolar dimensional changes with volumetric computed tomography.
The aim of this study is to present a predictable method for evaluating dimensional changes in the alveolar ridge through cone beam computed tomography (CT). Twenty subjects with single-rooted tooth extraction indication were selected for this preliminary report, which is part of a larger ongoing investigation. After extraction, two CT scans were performed; the first within 24 hours post-extraction (TC1) and the second 6 months (TC2) later. A radiographic guide with a radiopaque element placed along the tooth axis was developed to locate the same plane of reference in two different CT scans. For each patient, backtrack analysis was performed in order to establish the reproducibility error of a predetermined point in space between two CT scans. Briefly, an anatomical landmark was selected and its coordinates to the radiopaque marker were recorded. One week later, the coordinates were followed backwards in the same CT scan to obtain the position where the reference point should be located. A similar process was carried out between two different CT scans taken 6 months apart. The distance between the anatomical reference and the obtained point of position was calculated to establish the accuracy of the method. Additionally, a novel method for evaluating dimensional changes of the alveolus after tooth extraction is presented. The backtrack analysis determined an average within-examiner discrepancy between both measurements from the same CT scan of 0.19 mm. SD +/- 0.05. With the method presented herein, a reference point in a CT scan can be accurately backtracked and located in a second CT scan taken six months later. Taken together they open the possibility of calculating dimensional changes that occur in the alveolar ridge over time, such as post-extraction alveolar resorption, or the bone volume gained after different augmentation procedures.


Plasma Klotho concentration is associated with the presence, burden and progression of cerebral small vessel disease in patients with acute ischaemic stroke.
Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: -0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59-0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56-0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.


The effectiveness of balance training programs on reducing the incidence of ankle sprains in adolescent athletes.
Ankle sprains are one of the most common sport-related injuries treated by rehabilitation professionals. These injuries often result in lost participation and can lead to subsequent injury episodes. Therefore, it is important to determine appropriate means of preventing these injuries. There has recently been an increase in the popularity of balance training programs for the prevention of knee anterior cruciate ligament (ACL) injury, with some thought that starting these programs in younger athletes may be most beneficial. However, there is the potential that these types of training programs may also be beneficial for decreasing the risk of other lower extremity injuries, including ankle sprains in the adolescent athlete.


Improving Physical Activity among Residents of Affordable Housing: Is Active Design Enough?
Physical inactivity increases risk of chronic disease. Few studies examine how built environment interventions increase physical activity (PA). Active design (AD) utilizes strategies in affordable housing to improve resident health. We assessed how AD housing affects PA among low-income families in Brooklyn, New York. Participants were recruited at lease signings in 2016 from a new AD apartment complex and two recently renovated comparison buildings without AD features. Eligibility included age ≥18 years with no contraindications to exercise. Anthropometric data were collected. PA was self-reported using the Recent and Global Physical Activity Questionnaires. Smartphone users shared their tracked step. Data collection was repeated one year after move-in. All data were analyzed using SPSS. Eighty-eight eligible participants completed the initial questionnaire (36 AD and 52 from 2 comparison buildings) at baseline (T0). There were no differences between AD and comparison cohorts in: stair use, PA, sitting time or, mean waist-to-hip ratio (WHR) at T0. However, the AD cohort had a lower baseline BMI (27.6 vs. 31.0, p = 0.019). At one-year follow-up (T1), 75 participants completed our survey including a 64% retention rate among those who previously completed the T0 questionnaire. Among T0 questionnaire respondents, mean daily steps increased at T1 among AD participants who moved from an elevator building (∆6782, p = 0.051) and in the comparison group (∆2960, p = 0.023). Aggregate moderate work-related activity was higher at T1 in the AD building (746 vs. 401, p = 0.031). AD building women reported more work-related PA overall but AD men engaged in more moderate recreational PA. Living in an AD building can enhance low-income residents' PA. More research with objective measures is needed to identify strategies to sustain higher PA levels and overall health.


Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity.
Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8-10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short-term alginate treatment for weight loss.


Distal oblique metatarsal osteotomy technique in hallux valgus deformity: Clinical and radiological results.
This study aims to evaluate the radiological and functional outcomes of hallux valgus patients treated with distal oblique metatarsal osteotomy technique. Twenty-six feet of 22 patients (4 males, 18 females; mean age 46.2±18 years; range, 16 to 70 years) who were diagnosed as hallux valgus between March 2013 and April 2016 and who underwent distal oblique metatarsal osteotomy were included in this retrospective study. American Orthopedic Foot and Ankle Society/Hallux Metatarsophalangeal-Interphalangeal Scale (AOFAS/HMIS) was used for clinical and functional evaluation. The hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), sesamoid position, first metatarsal length and forefoot bone and soft tissue width were measured for radiological evaluation. The mean follow-up time was 33.1±9.8 months. The AOFAS/HMIS score increased significantly postoperatively (p=0.001). In the footwear section of the AOFAS/HMIS, the median preoperative score of 5 (range, 0-5) increased to 10 (range, 5-10) at the postoperative period (p=0.001). Hallux valgus angle, IMA, DMAA, and first metatarsal length significantly decreased when compared to preoperative measurements. Forefoot bone width also decreased significantly from 9.3 cm (range, 7.5-11.5 cm) to 8.8 cm (6.8-10.3 cm) (p=0.001). Distal oblique metatarsal osteotomy is a safe method for hallux valgus deformity. Forefoot width reduction, decrease of soft tissue tension, sesamoid reduction, and plantar fascia relaxation are the crucial benefits of this method.


Galactoside-proton symport in a lacYUN mutant of Escherichia coli investigated by analysis of transport progress curves.
The kinetics of galactoside-proton symport catalysed by a wild-type strain and one carrying a mutation, previously reported to cause uncoupling of the symport reaction, have been examined. The mutation does not affect the stoichiometry during the initial period of uptake, when the internal concentration of galactoside is low, but it does result in much greater competition from the galactoside as it is accumulated. Simple methods for the analysis of the uptake progress curves have been developed and used to estimate the initial rate of uptake and affinity for internal galactoside. The maximum rate of uptake is decreased by a factor of 2 at most whereas the affinity for internal galactoside is increased up to 50-fold by the mutation. The pH-dependence of the galactoside efflux reaction is changed in a manner which suggests that the defect is in the interaction between proton-binding and galactoside-binding sites rather than in the structure of either site.


Gender preference and perinatal depression in Turkey: A cohort study.
Child gender preference is important in some cultures and has been found to modify risk for antenatal and postnatal depression. We investigated discrepancies in the child gender preference between participating women and other key family members and the extent to which these predicted perinatal depression. In a large cohort study of perinatal depression in urban and rural Turkey, participants had been asked about child gender preferences: their own, and those of their husband, parents, and parents in-law. Of 730 participants recruited in their third trimester (94.6% participation), 578 (79.2%) were reassessed at a mean (SD) 4.1 (3.3) months after childbirth, and 488 (66.8%) were reassessed at 13.7 (2.9) months. No associations were found between any gender preference reported in the antenatal period and depression at any examination. On the other hand, we found associations of antenatal depression with differences in participant-reported gender preference and that reported for their mother-in-law (OR 1.81, 1.08-3.04). This non-agreement also predicted depression at the 4 month (OR 2.24, 1.24-4.03) and 14 month (OR 2.07, 1.05-4.04) post-natal examinations. These associations with postnatal depression persisted after adjustment for a range of covariates (ORs 3.19 (1.54-6.59) and 3.30 (1.49-7.33) respectively). Reported disagreement in child gender preferences between a woman and her mother-in-law was a predictor of post-natal depression and may reflect wider family disharmony as an underlying factor.


Non-uniformity of Changes in Drug-Metabolizing Enzymes and Transporters in Liver Cirrhosis: Implications for Drug Dosage Adjustment.
Liver cirrhosis is a chronic disease that affects the liver structure, protein expression, and overall metabolic function. Abundance data for drug-metabolizing enzymes and transporters (DMET) across all stages of disease severity are scarce. Levels of these proteins are crucial for the accurate prediction of drug clearance in hepatically impaired patients using physiologically based pharmacokinetic (PBPK) models, which can be used to guide the selection of more precise dosing. This study aimed to experimentally quantify these proteins in human liver samples and assess how they can impact the predictive performance of the PBPK models. We determined the absolute abundance of 51 DMET proteins in human liver microsomes across the three degrees of cirrhosis severity (n = 32; 6 mild, 13 moderate, and 13 severe), compared to histologically normal controls (n = 14), using QconCAT-based targeted proteomics. The results revealed a significant but non-uniform reduction in the abundance of enzymes and transporters, from control, by 30-50% in mild, 40-70% in moderate, and 50-90% in severe cirrhosis groups. Cancer and/or non-alcoholic fatty liver disease-related cirrhosis showed larger deterioration in levels of CYP3A4, 2C8, 2E1, 1A6, UGT2B4/7, CES1, FMO3/5, EPHX1, MGST1/3, BSEP, and OATP2B1 than the cholestasis set. Drug-specific pathways together with non-uniform changes of abundance across the enzymes and transporters under various degrees of cirrhosis necessitate the use of PBPK models. As case examples, such models for repaglinide, dabigatran, and zidovudine were successful in recovering disease-related alterations in drug exposure. In conclusion, the current study provides the biological rationale behind the absence of a single dose adjustment formula for all drugs in cirrhosis and demonstrates the utility of proteomics-informed PBPK modeling for drug-specific dose adjustment in liver cirrhosis.


Orbicularis oculi reflex and facial muscle electromyography. Pre- and postoperative evaluation of posterior fossa space-occupying lesions.
The electrically evoked orbicularis oculi reflex was analyzed in 26 patients with proven posterior fossa space-occupying lesions (11 cerebellopontine angle and 15 cerebellar hemispheric masses). In the former group, although only six had clinical evidence of trigeminal or facial involvement, the reflex analysis showed both nerves to be involved in all. Electromyography (EMG) of the orbicularis oculi showed profound denervation of this muscle while only minimal abnormalities of the masseter were seen. The sensory component of the trigeminal nerve was always more involved than its motor component and this was a reliable guide as to the upward and medial extension of the tumor, especially in the absence of clinical localizing signs. In the 15 patients with cerebellar masses, six with masses located posteriorly and entirely within the confines of the cerebellum had normal studies. In eight, the mass was located anteriorly, and fifth nerve involvement could be detected in all by EMG, although only two patients had clinical evidence of such involvement. One patient with dysfunction of the central reflex arc had EMG evidence of an intraventricular dermoid tumor abutting the pons, later confirmed at surgery. Thus, an invaluable body of diagnostic and prognostic data can be obtained by this nontraumatic and simple electrodiagnostic procedure.


Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling.
Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and PAMPs on DCs. This affects DC effector function, as demonstrated by the finding that C5a prevents induction of pro-inflammatory cytokines by toll-like receptor (TLR) ligands in human monocyte-derived DCs (moDCs). Here, we demonstrate that this regulatory crosstalk is specifically important in 6-sulfo LacNAc dendritic cells (slanDCs), the most pro-inflammatory DC subset found in human. C5aR and TLR signaling show profound interference in the ERK/p38/CREB1 signaling pathways. C5aR signaling accelerates TLR-induced CREB1 phosphorylation both in moDC and slanDC. This is key in the regulatory effect of C5a on pro-inflammatory DC maturation by mediating induction of IL-10, which subsequently inhibits pro-inflammatory cytokine production via negative feedback signaling. Importantly, the regulatory effect of C5a affects T-cell immunity by decreasing Th1 and cytotoxic CD8 T-cell responses. The finding that the pro-inflammatory effector function of slanDC can be down modulated by activation products of the complement system highlights the existence of intricate regulatory interactions between various arms of the immune system. Intensive immune monitoring of patients suffering from complement-mediated diseases or patients receiving complement modulating compounds can give more inside in the contribution of complement receptor and TLR crosstalk in APCs in disease.


Investigation of the survival characteristics of Rhodococcus coprophilus and certain fecal indicator bacteria.
Rhodococcus coprophilus and Clostridium perfringens survived in fresh water samples held at 5, 20, and 30 degrees C for over 17 weeks, whereas Escherichia coli and fecal streptococci disappeared after 5 weeks at all three temperatures. R. coprophilus survived for more than 8 months in sterilized sewage and deionized water at all three temperatures, whereas in normal sewage held at 20 degrees C, the survival time was 12 to 26 weeks. In samples held at 30 degrees C, survival times were shorter, probably because of interbacterial competition or protozoal predation. The results indicate that R. coprophilus may be a useful indicator of the presence of remote fecal pollution of farm animal origin, but not of recent pollution, when enumerated alone in polluted waters or wastewaters.


Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.
We investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study. In total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated. Using the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n = 61) had significantly lower BVAS (P = 0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n = 95). MPO-ANCA-positive MPA/RLV is the most common form of AAV in Japanese patients, and one-half of patients with GPA were positive for MPO-ANCA. ILD is an important clinical manifestation in Japanese patients with AAV. Unclassifiable vasculitis with MPO-ANCA positivity and ILD may represent a novel variant of MPA. The University Hospital Medical Information Network Clinical Trials Registry: UMIN000001648. Registered 28 February 2009.


Procrastination predicts online self-regulated learning and online learning ineffectiveness during the coronavirus lockdown.
During the lockdown due to SARS-CoV-2 (coronavirus lockdown), there has been a tremendous increase in the number of students taking online courses. Few studies, however, have examined the individual dispositions that influence self-regulated online learning during the coronavirus lockdown. To address this gap, the present study explored the ineffectiveness of online learning and examined how it can be predicted by self-regulated online learning and participants' procrastination disposition. Data of 433 participants were collected and subjected to confirmatory factor analysis with structural equation modeling. The results indicated that procrastination is negatively related to 6 sub-constructs of self-regulated online learning: task strategy, mood adjustment, self-evaluation, environmental structure, time management, and help-seeking. These sub-constructs were negatively related to the learners' perceived ineffectiveness of online learning. However, the relationship between perceived learning ineffectiveness and environmental structure or help-seeking was weaker than that with task strategy or mood adjustment, indicating that the latter two subtypes of self-regulated online learning should be considered before students engage in online learning.


Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.
An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities.


Toward the development of antibacterial vaccines: report of a symposium and workshop. Organizing Committee.
On 26 and 27 October 1998, the Department of Medicine at the University of California, San Francisco (UCSF), hosted a symposium and workshop on bacterial vaccines. The symposium featured invited speakers who are internationally recognized authorities in their fields and who discussed selected topics related to specific pathogens or specific principles of bacterial vaccine development. The workshop, held on the day following the symposium, brought together the invited speakers and members of the organizing committee, who came from UCSF and the University of California, Berkeley, to discuss 4 specific topics and to define priorities for future vaccine development. Considerable knowledge has been gained from successful and unsuccessful vaccine development efforts, and large gains in knowledge relevant to vaccine development have resulted from studies of basic immunology and microbial pathogenesis. This report summarizes the presentations at the symposium and the discussions of the workshop sessions.


Initial and mid-term results from 108 consecutive patients with cerebral aneurysms treated with the WEB device.
The Woven EndoBridge (WEB) is a novel device for the treatment of wide-necked intracranial bifurcation aneurysms. The present series demonstrates our 'real-world experience' in the use of all iterations of WEB devices (available in Europe) in ruptured and unruptured aneurysms. We analyzed our all-inclusive cerebrovascular database for patients treated with the WEB device between October 2010 and May 2015. Anatomic and clinical results are reported for all patients. One hundred and eight patients with 114 intracranial aneurysms were included in the series. Forty-seven aneurysms (41.2%) were ruptured. Eighty-six patients received angiographic and clinical follow-up after a mean of 13.4 months. One hundred and ten of 114 WEB devices (96.5%) were deployed successfully. Thromboembolic complications occurred in 11 of 110 interventions (10.0%), with a new permanent deficit in one patient. Re-rupture after WEB treatment was detected in two aneurysms (4.3%), which had both initially presented with subarachnoid hemorrhage. Angiographic follow-up revealed adequate occlusion in 68 of 90 aneurysms (75.6%). Fifteen aneurysms required retreatment. This series confirms a high level of safety and efficacy of the WEB device for the treatment of wide-necked intracranial aneurysms.


The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment.DOI:http://dx.doi.org/10.7554/eLife.00070.001.


[The role of rotary prisms and dynamic color stimuli in binocular vision recovery in children with squint].
A modified procedure for diploid treatment is proposed to disinhibit a functional scotoma and to develop binocular vision (BV) in children with squint. The procedure is to examine a special test object through rotary prisms and polaroid filters inserted into a modernized spectacle frame. During treatment there is an opportunity of simultaneously changing the color of the test object and the position of its image on the retina. The study enrolled children in whom previous traditional methods for BV recovery had failed. Treatment using the proposed procedure could recover bifoveal fusion in 88.3% of cases (as evidenced by synoptophore examination) and BY in 73.3% (as shown by scanning haploscopy).


Role of beta-lactamases in the response of pulmonary infections to amoxycillin/clavulanate.
Lung secretions from patients with bronchiectasis have been studied before and during treatment with amoxycillin/clavulanate (Augmentin 750 mg tds). beta-Lactamase activity was usually present in the sputum sol phase and originated from organisms not usually considered to be the major pathogen. The presence of beta-lactamase was related to inactivation of amoxycillin in the lung secretions. Extensive bacteriological investigation of the sputum before therapy showed several organisms to be present in each sample. Six of eight patients showed a good clinical and biochemical response to therapy with amoxycillin/clavulanate. This, however, could not be predicted or explained by the results of bacterial investigation although Haemophilus influenzae was eradicated in three of these responders. beta-Lactamase activity did not change during treatment, and this investigation thus failed to produce indirect evidence of penetration of clavulanate into the secretions.


Comparative assessment of net CO2 exchange across an urbanization gradient in Korea based on eddy covariance measurements.
It is important to quantify changes in CO2 sources and sinks with land use and land cover change. In the last several decades, carbon sources and sinks in East Asia have been altered by intensive land cover changes due to rapid economic growth and related urbanization. To understand impact of urbanization on carbon cycle in the monsoon Asia, we analyze net CO2 exchanges for various land cover types across an urbanization gradient in Korea covering high-rise high-density residential, suburban, cropland, and subtropical forest areas. Our analysis demonstrates that the urban residential and suburban areas are constant CO2 sources throughout the year (2.75 and 1.02 kg C m-2 year-1 at the urban and suburban sites), and the net CO2 emission indicate impacts of urban vegetation that responds to the seasonal progression of the monsoon. However, the total random uncertainties of measurement are much larger in the urban and suburban areas than at the nonurban sites, which can make it challenging to obtain accurate urban flux measurements. The cropland and forest sites are strong carbon sinks because of a double-cropping system and favorable climate conditions during the study period, respectively (- 0.73 and - 0.60 kg C m-2 year-1 at the cropland and forest sites, respectively). The urban area of high population density (15,000 persons km-2) shows a relatively weak CO2 emission rate per capita (0.7 t CO2 year-1 person-1), especially in winter because of a district heating system and smaller traffic volume. The suburban area shows larger net CO2 emissions per capita (4.9 t CO2 year-1 person-1) because of a high traffic volume, despite a smaller building fraction and population density (770 persons km-2). We show that in situ flux observation is challenging because of its larger random uncertainty and this larger uncertainty should be carefully considered in urban studies. Our findings indicate the important role of urban vegetation in the carbon balance and its interaction with the monsoon activity in East Asia. Urban planning in the monsoon Asia must consider interaction on change in the monsoon activity and urban structure and function for sustainable city in a changing climate.


Identification of a novel WxSLVK motif in the N terminus of human immunodeficiency virus and simian immunodeficiency virus Vif that is critical for APOBEC3G and APOBEC3F neutralization.
The function of lentiviral Vif proteins is to neutralize the host antiviral cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F). Vif bridges a cullin 5-based E3 ubiquitin ligase with A3G and A3F and mediates their degradation by proteasomes. Recent studies have found that Vif uses different domains to bind to A3G and A3F. A (14)DRMR(17) domain binds to A3F, (40)YRHHY(44) binds to A3G, and (69)YxxL(72) binds to both A3G and A3F. Here, we report another functional domain of Vif. Previously, we demonstrated that human immunodeficiency virus type 1 (HIV-1) Vif failed to mediate A3G proteasomal degradation when all 16 lysines were mutated to arginines. Here, we show that K26, and to a lesser extent K22, is critical for A3G neutralization. K22 and K26 are part of a conserved (21)WxSLVK(26) (x represents N, K, or H) motif that is found in most primate lentiviruses and that shows species-specific variation. Both K22 and K26 in this motif regulated Vif specificity only for A3G, whereas the SLV residues regulated Vif specificity for both A3F and A3G. Interestingly, SLV and K26 in HIV-1 Vif did not directly mediate Vif interaction with either A3G or A3F. Previously, other groups have reported an important role for W21 in A3F and A3G neutralization. Thus, (21)WxSLVK(26) is a novel functional domain that regulates Vif activity toward both A3F and A3G and is a potential drug target to inhibit Vif activity and block HIV-1 replication.


Mass Culture of Phytoplankton as Foods for Metazoans.
An apparatus for mass culture of photosynthetic microorganisms has been developed to grow algae for use as foods for larval and juvenile mollusks in studies of their physiological requirements. The apparatus consists of a series of 5-gal growth chambers, and the system can be enlarged to yield any desired volume of algae by replication of basic units. Approximately 50 lit. of algal suspension, averaging about 0.5 ml of packed wet cells per liter, are produced daily.


Radio studies of extragalactic supernovae.
Some exploding stars (supernovae) are powerful emitters of centimeter radio radiation. Detailed observations have shown that these supernovae quickly become detectable in the radio range, first at shorter wavelengths (higher frequencies) and later at progressively longer and longer wavelengths (lower frequencies). This part of the phenomenon appears to be well explained by a monotonic decrease in the amount of ionized material surrounding the radio-emitting regions as the shock from the explosion travels outward. The radio emission itself is of a nonthermal, synchrotron origin, as is the case in most bright cosmic radio sources. Once the absorption effects become negligible, the radio intensity declines with time until reaching the detection limit of the telescope. Models suggest that the absorbing material originates in a dense wind of matter lost by the supernova progenitor star, or by its companion if it is in a binary system, in the last stages of evolution before the explosion. The synchrotron radio emission can be generated either externally by the shock wave from the explosion propagating through this same high density stellar wind or internally by a rapidly rotating neutron star, which is the collapsed core of the exploded star. Present results appear to favor the former model for at least the first several years after the supernova explosion, although the latter model remains viable.


Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.
Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for gamma(c)'s ability to recognize six different gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13R alpha1 for a novel mode of cytokine engagement that contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.


Biomechanical studies of elite female distance runners.
The experiments showed the elite women runners to be predominantly midfoot strikers. Their ground reaction forces showed peaks of 3.3 times body weight in the vertical component, 0.8 times body weight in the braking phase, and 0.3 times body weight in the mediolateral direction. The asymmetry in their ground reaction forces was expressed mainly in the mediolateral component. Only minor differences were found between ground reaction forces in racing and training shoes. More abduction during foot placement was associated with greater rearfoot motion and with greater change in mediolateral component of velocity. Among the numerous moderate to high correlations of interest were those between vertical oscillation and peak vertical force, crossover and change in mediolateral velocity, and between movements of the swing leg and mediolateral force values. There were very few correlations between running economy and biomechanical variables, and stride length correlated poorly with stature. The elite runners were shorter in stature, lighter, had shorter legs and considerably less iliac crest fat than a typical non-athletic female population. The runners also had narrower pelves than a student population of similar age. They were reasonably homogeneous and symmetrical in anthropometric dimensions. Compared with a group of elite male runners at the same running velocity, the elite women exhibited more hip flexion, greater angular velocities in hip flexion and extension, and longer stride lengths relative to leg length during running. Their vertical oscillation (expressed relative to leg length) was less than that shown by their male counterparts. On the issue of relative pelvic width, the women had greater relative bitrochanteric and bi-iliac crest widths but similar bispinous widths compared to the elite male runners (all values expressed relative to leg length). Clearly the issue of male-female pelvic width differences at the elite level is not as simple as had previously been suggested.


Efficacy of perioperative high-dose prednisolone therapy during thymectomy in myasthenia gravis patients.
This study aimed to investigate the benefits of administering perioperative high-dose prednisolone in conjunction with thymectomy in patients with myasthenia gravis. We retrospectively reviewed data from patients with Myasthenia Gravis Foundation of America Clinical Class I to IIIB who had undergone an extended thymectomy between 1992 and 2009. Perioperative high-dose prednisolone was administered at starting doses of 10 to 20 mg and escalated up to 100 mg on alternate days. The treatment group comprised 70 patients receiving perioperative high-dose prednisolone, whereas the control group included 61 patients not treated with preoperative steroids. The two groups were compared with respect to baseline clinical characteristics, incidence of postoperative complications, and follow-up disease status. Prednisolone-treated patients presented with more advanced disease compared to controls (Class IIB or greater, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001). Mean preoperative%FVC was lower and FEV1.0% was higher in treated patients than in controls (%FVC: 92.4 ± 2.3% versus 99.5 ± 2.4%, respectively; P = 0.037, FEV1.0%: 85.2 ± 1.3% versus 81.4 ± 0.9%, respectively; P = 0.017). The groups were similar in other variables including presence of thymoma, and operative procedure. In the treatment group, disease status was significantly improved only by the induction of high-dose prednisolone before the surgery (P < 0.001), and these patients discontinued anti-cholinesterase therapy more frequently than controls (P < 0.001). Moreover, the treatment group demonstrated markedly lower rates of postoperative crisis (12.2% versus 2.9%, respectively; P = 0.045). The incidence of infection, wound dehiscence, and diabetes mellitus were comparable between groups. Survival analysis demonstrated higher rates of treated patients with improved disease status at three and five years (92% and 96%, respectively) compared to controls (57% and 76%, respectively; P < 0.001). Likewise, significantly greater proportions of treated patients achieved complete stable remission or pharmacologic remission at three, five, and ten years (23%, 42%, and 72%, respectively) compared to controls (10%, 20%, and 44%, respectively; P = 0.002). Perioperative high-dose prednisolone therapy is a safe, promising strategy for managing patients with myasthenia gravis and may reduce the incidence of postoperative crisis while improving disease status.


Linkage of type I interferon activity and TNF-alpha levels in serum with sarcoidosis manifestations and ancestry.
Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes. We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations. Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups. Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.


[Environmental impact of tobacco].
Tobacco has not only negative effects on health; it also has an environmental impact. Each year, tobacco production requires 22 000 billion liters of water, mainly for cultivation. Thousands hectares of forestland are cleared annually, largely for the desiccation of tobacco leaves. Cigarette production is responsible for 84 million tons of CO2 equivalent. This paper reviews the environmental impact of the production and consumption of cigarettes from tobacco growing and manufacturing to consumption and waste production, and compares it with current consumption data.


Risk indicators associated with subclinical mastitis in smallholder dairy cows in Tanzania.
Smallholder dairy farmers in Tanzania appear to be unaware of the subclinical mastitis situation in their cows. A cross-sectional study was carried out between June and September 2002 on smallholder dairy herds in the Dar es Salaam region. The study objectives were to establish the prevalence of subclinical mastitis and related risk indicators, and to assess their contribution to the occurrence of subclinical mastitis. Three field procedures based on the principles of herd health and production management were followed: clinical, farm and data inspection. The California mastitis test (CMT) was carried out on quarter milk samples to determine the prevalence of subclinical mastitis. A total of 182 lactating cows from 62 herds were investigated. Clinical inspection indicated that 3.8% of the lactating cows had clinical mastitis. Subclinical mastitis was detected in 90.3% of lactating cows screened. Farm inspection revealed that water scarcity, barn size, residual suckling, single udder-towel and dairy labourers as the most substantial (p < 0.05) risk indicators. Although most of the risk indicators studied were not found to be statistically significantly associated with the occurrence of subclinical mastitis, possibly owing to sample size and the presence of confounders, the epidemiological need to address such risk indicators cannot be overemphasized.


Antibacterial and cytotoxic activities of phenolic constituents from the stem extracts of Spatholobus parviflorus.
A new 2-arylbenzofuran, spathobenzofuran (1), together with ten known compounds including a 2-arylbenzofuran, three pterocarpans and six isoflavones were isolated from the acetone crude extract of the stems of Spatholobus parviflorus. All compounds were characterised by spectroscopic methods. Compound 4 was active (MIC 8 µg/mL) against Gram-negative Pseudomonas aeruginosa TISTR 781 while compound 2 had modest activity against Gram-positive Staphylococcus aureus TISTR 1466 with a MIC value of 16 µg/mL. All isolated compounds showed no cytotoxicity against Vero and KB cells.


Teaching residents: critical appraisal of the literature using a journal club format.
Critical appraisal of the literature is an integral and important part of surgical practice, but can this skill be taught to young doctors? The purpose of this study was to investigate the effect of formal instruction regarding critical review and appraisal of journal articles, using junior surgical residents followed over the course of a 10-week long programme. First-year surgical residents who participated in the department of orthopaedic surgery's compulsory journal club evaluated one article per week for 10 weeks, using the reviewer guidelines and a scoring system currently used by Arthroscopy. The article was selected by a senior consultant orthopaedic surgeon and was provided for assessment to each resident the week prior. The scores and evaluation recommendation (accept, revise and reject) of the residents were then compared against the senior surgeon's assessment. A contingency table and Fisher's exact test was used to compare the frequency of agreement between the decisions of the senior surgeon and the residents. Twenty residents were included. Agreement in overall total assessment scores increased significantly (p=0.0001) from 49.5% at session 1 to 82.5% at session 10. When comparing the mean percentage of agreement of the first five sessions (61%) with the second five sessions (95%), a significant (p=0.03) increase was observed. The percentage of agreement with the senior surgeon (whether the article should be accepted, revised or rejected) improved from 0% for the first session to 60% at the last session (χ2=7.2-11.2, p=0.02-0.04). The results strongly suggest that a structured approach to the review and appraisal of journal articles using the format of a journal club significantly improves critical reading skills for first-year surgical residents.


[Antipyrine test in evaluation of patient's hepatic failure in early postoperative period].
In victims of severe combined trauma in early postoperative period there are disorders in the system of monooxygenase detoxication of hepatocytes--the duration of antipyrine semiexcretion period in the blood was 2.5 times longer than in healthy people. In 40% of injured parallelism in changes of values of the antipyrine test and general blood bilirubin are detected; in 18% of cases hyperbilirubinemia is revealed in antipyrine clearence being normal, and in 42% a sharp decrease of antipyrine clearence at the background of normal bilirubin content is detected. Hypoproteinemia, hypoalbuminuria, and activation of ALT and AST was revealed, which evidenced of the reaction of urgent adaptation. Under conditions of development of the postoperative stress-reaction the examination of monooxygenaze system of hepatocytes' detoxication is the most specific test of revealing early hepatic insufficiency. A sharp decrease or increase of antipyrine clearence is a sign of irreversibility of hepatic insufficiency.


Subtypes of illicit drug users: a latent class analysis of data from an Australian twin sample.
This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.


Physical and hormonal evaluation of transsexual patients: a longitudinal study.
The physical and hormonal characteristics of 60 male-to-female transsexuals and 30 female-to-male transsexuals were measured before or during treatment with commonly used forms and dosages of hormones. Only two patients (both female-to-male) had either a congenital defect in hormonal production or abnormal genital development. Patients were seen at 3- to 6-month intervals for an average of 18 months. The response to therapy was examined over time; physical parameters, hormonal concentrations, liver function tests, lipids, and glucose were measured. Three patients were changed from ethinyl estradiol to conjugated estrogen because of liver enzyme elevations. Ethinyl estradiol (0.1-0.5 mg/day) was equal to conjugated estrogen (7.5-10 mg/day) in its ability to suppress testosterone and gonadotropins and to promote breast growth. Maximum breast growth required 2 years of therapy. During treatment with testosterone, female-to-male transsexuals had a significant mild elevation of cholesterol and triglyceride. The female-to-male transsexuals receiving testosterone cypionate, 200 mg every 2 weeks, ceased to have menstrual periods and became progressively masculinized. A mean maximal clitoral length of 4.6 cm which achieved by 1 year of therapy. Based on the data generated by this study, we recommend as hormonal therapy 0.1-0.5 mg/day of ethinyl estradiol or 7.5-10 mg/day of conjugated estrogen for male-to-female transsexuals, and intramuscular testosterone cypionate, 200 mg every 2 weeks, for female-to-male transsexuals.


Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins.
Although statin treatment is generally well tolerated, it is estimated that 5% to 10% of patients develop muscle-related side effects (MRSEs), resulting in less effective nonstatin alternatives or cessation of lipid-lowering therapy completely. This study was designed to assess the efficacy and tolerability of extended-release fluvastatin (fluvastatin XL) and ezetimibe alone or in combination in patients with previous MRSEs with other statins. This was a double-blinded, double-dummy trial of 199 mostly moderate- or high-risk dyslipidemic patients randomized to fluvastatin XL 80 mg/day (n = 69), ezetimibe 10 mg/day (n = 66), or fluvastatin XL 80 mg/day plus ezetimibe 10 mg/day (n = 64) for 12 weeks. Fluvastatin XL lowered low-density lipoprotein (LDL) cholesterol by 32.8% compared with 15.6% with ezetimibe (between-group difference -17.1%, 95% confidence interval -23.6 to -10.7, p <0.0001); the fluvastatin XL/ezetimibe combination lowered LDL cholesterol by 46.1% (between-group difference vs ezetimibe -30.4%, 95% confidence interval -37.0 to -23.8, p <0.0001). Proportions of patients achieving their National Cholesterol Education Program Adult Treatment Panel III target LDL cholesterol were 84% with the fluvastatin XL/ezetimibe combination, 59% with fluvastatin XL, and 29% with ezetimibe (p <0.001 for fluvastatin XL monotherapy or combination therapy vs ezetimibe monotherapy). Incidences of MRSEs were 24% in the ezetimibe group, 17% in the fluvastatin XL group, and 14% in the combination group. There were no instances of creatine kinase increases >or=10 times upper limit of normal. In conclusion, in patients with a history of statin-associated MRSEs, fluvastatin XL alone or in combination with ezetimibe offers an effective and well-tolerated lipid-lowering option.


[Nocturnal symptoms of Parkinson's disease and approaches to their correction].
Seventy-three patients with Parkinson's disease were enrolled. Patients were stratified into 2 groups by the presence (53 patients) or absence (20 patients) of nocturnal symptoms. A control group included 10 healthy people. The most frequent were the following symptoms: nocturia (71.8%), affective disorders (52.4%), akinesia (41.7%) and crampi (30.15%). These symptoms were more pronounced in akinetic/rigid form, greater severity and higher rate of progression of the disease. The positive therapeutic effect of stalevo on the above mentioned disorders was shown.


[History of surgery in the Czech Republic and evolution of Czech surgery clinics].
The author presents a brief of the position of the surgery during centuries in Czech. He mentions the conditions for university education of the surgery since 1848. In 1860 the Czech Medical Society was founded and in 1862 the first issue of the Czech Medical Journal (Casopis lékarů ceských) was published. The first Czech lecture was made on 28th April 1882 on the Czech surgery clinic. The climax of Czech desires of revival was the separation of Czech and German clinics in 1882. The development of some medical disciplines, incl. surgical disciplines, made the surgeons abandon the Czech Medical Society and after the establishment of the committee of the Czechoslovak Republic they founded in 1920 the committee of the Czechoslovak Society for Surgery and Gynaecology. There is explained origin of title MUDr., so typical for graduated students on Prague Medical Faculty. The First Surgery Clinic (founded in 1920) of the Charles University and General Hospital in Prague is continuator of the Czech surgery clinic.


Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage.
Cancer prevention is a cost-effective alternative to treatment. In mice, the mTOR inhibitor rapamycin prevents distinct spontaneous, noninflammatory cancers, making it a candidate broad-spectrum cancer prevention agent. We now show that oral microencapsulated rapamycin (eRapa) prevents skin cancer in dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) carcinogen-induced, inflammation-driven carcinogenesis. eRapa given before DMBA/TPA exposure significantly increased tumor latency, reduced papilloma prevalence and numbers, and completely inhibited malignant degeneration into squamous cell carcinoma. Rapamycin is primarily an mTORC1-specific inhibitor, but eRapa did not reduce mTORC1 signaling in skin or papillomas, and did not reduce important proinflammatory factors in this model, including p-Stat3, IL17A, IL23, IL12, IL1β, IL6, or TNFα. In support of lack of mTORC1 inhibition, eRapa did not reduce numbers or proliferation of CD45(-)CD34(+)CD49f(mid) skin cancer initiating stem cells in vivo and marginally reduced epidermal hyperplasia. Interestingly, eRapa reduced DMBA/TPA-induced skin DNA damage and the hras codon 61 mutation that specifically drives carcinogenesis in this model, suggesting reduction of DNA damage as a cancer prevention mechanism. In support, cancer prevention and DNA damage reduction effects were lost when eRapa was given after DMBA-induced DNA damage in vivo. eRapa afforded picomolar concentrations of rapamycin in skin of DMBA/TPA-exposed mice, concentrations that also reduced DMBA-induced DNA damage in mouse and human fibroblasts in vitro. Thus, we have identified DNA damage reduction as a novel mechanism by which rapamycin can prevent cancer, which could lay the foundation for its use as a cancer prevention agent in selected human populations.


MOMS: maximal-order interpolation of minimal support.
We consider the problem of interpolating a signal using a linear combination of shifted versions of a compactly-supported basis function phi(x). We first give the expression for the cases of phi's that have minimal support for a given accuracy (also known as "approximation order"). This class of functions, which we call maximal-order-minimal-support functions (MOMS) is made of linear combinations of the B-spline of the same order and of its derivatives. We provide an explicit form of the MOMS that maximizes the approximation accuracy when the step-size is small enough. We compute the sampling gain obtained by using these optimal basis functions over the splines of the same order. We show that it is already substantial for small orders and that it further increases with the approximation order L. When L is large, this sampling gain becomes linear; more specifically, its exact asymptotic expression is 2/(pie)L. Since the optimal functions are continuous, but not differentiable, for even orders, and even only piecewise continuous for odd orders, our result implies that regularity has little to do with approximating performance. These theoretical findings are corroborated by experimental evidence that involves compounded rotations of images.


Coumarins: Auspicious Cholinesterase and Monoamine Oxidase Inhibitors.
Cholinesterase inhibition is the only current validated target in clinics in the treatment of Alzheimer's disease (AD). Therefore, there is continuous interest in the development and discovery of novel cholinesterase inhibitory molecules. Coumarins, beside their employment in other pharmacological groups, have also attracted attention to be utilized in cholinesterase inhibitory molecule discovery and development. Numerous studies so far indicated the natural and synthetic coumarin analogues that have the potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes. Since the pathophysiology of AD is highly complex and, in particular, monoamine oxidase (MAO) inhibitors are also utilized in clinic for disease symptoms, coumarin analogues, either natural or synthetic, that have the potential to inhibit cholinesterase or MAO enzymes are summarized within this review.


Electrophysiologically "complex" glial cells freshly isolated from the hippocampus are immunopositive for the chondroitin sulfate proteoglycan NG2.
We have recently described a subgroup of isolated glial fibrillary acidic protein-positive (GFAP+) hippocampal astrocytes that predominantly express outwardly rectifying currents (which we term "ORAs" for outwardly rectifying astrocytes), which are similar to the currents already described for hippocampal GFAP- "complex glia." We now report that post-recording staining of cells that were first selected as "complex" by morphology and then confirmed by their electrophysiological characteristics were NG2+ approximately 90% of the time. Also, the morphology of freshly isolated NG2+ cells differs from that of isolated GFAP+ ORAs in having a smaller and round cell body with thinner processes, which usually are collapsed back onto the soma. Upon detailed examination, NG2+ cells were found to differ quantitatively in some electrophysiological characteristics from GFAP+ ORAs. The outward, transient K+ currents (IKa) in the NG2+ cells showed a slower decay than the IKa in ORAs, and their density decreased in NG2+ cells from older animals. The other two major cation currents, the voltage-activated Na+ and outwardly delayed rectifier K+ currents, were similar in NG2+ cells and ORAs. To further distinguish isolated complex cells from outwardly rectifying GFAP+ astrocytes, we performed immunocytochemistry for glial markers in fixed, freshly isolated rat hippocampal glia. NG2+ cells were negative for GFAP and also for the astrocytic glutamate transporters GLT-1 and GLAST. Thus the isolated hippocampal NG2+ glial cells, though having an electrophysiological phenotype similar to that of ORAs, are an immunologically and morphologically distinct glial cell population and most likely represent NG2+ cells in situ.


Congestive heart failure in patients with chronic kidney disease and on dialysis.
CHF is highly prevalent in ESRD and is a leading cause of death in such patients. Hypertension, renal anemia, and comorbid conditions such as coronary artery disease are particularly important risk factors for CHF in ESRD. Dialysis hypotension may be a marker of poor prognosis in such persons. Recent studies suggest that lipid peroxidation and L-carnitine deficiency may contribute to CHF in some patients with ESRD. All forms of renal replacement therapy are capable of ameliorating symptoms of CHF, but their effect on cardiovascular mortality has not been firmly established. Drug therapy, particularly angiotensin-converting enzyme inhibitors and beta-adrenergic receptor blockers, is under-used in patients with ESRD and CHF. Heart/kidney transplantation may be a viable option for some patients with advanced CHF and ESRD.


The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis.
To review the platelet-activating factor (PAF) signaling system, its regulation, and its dysregulation in acute inflammation and thrombosis and in syndromes that involve these cascades, including sepsis. A summary of published literature from MEDLINE search files and published reviews. DATA EXTRACTION, SYNTHESIS, AND SUMMARY: PAF, a phospholipid signaling molecule, transmits outside-in signals to intracellular transduction systems and effector mechanisms in a variety of cell types, including key cells of the innate immune and hemostatic systems: neutrophils, monocytes, and platelets. Thus, the PAF signaling system is a point of convergence at which injurious stimuli can trigger and amplify both acute inflammatory and thrombotic cascades. The biological activities of PAF are regulated by several precise mechanisms that, together, constrain and control its action in physiologic inflammation. Unregulated synthesis of PAF or defects in the mechanisms that limit its biological activities have the potential to cause pathologic inflammation and thrombosis. In addition, nonenzymatic generation of oxidized phospholipids that are recognized by the PAF receptor can trigger inflammatory and thrombotic events. There is evidence that the PAF signaling system is dysregulated in sepsis, shock, and traumatic injury and that interruption or termination of its effector responses leads to beneficial outcomes. Plasma PAF acetylhydrolase, an enzyme that hydrolyzes PAF and structurally related oxidized phospholipids, yielding products that are no longer recognized by the PAF receptor, may be a particularly important signal terminator. The PAF signaling system can trigger inflammatory and thrombotic cascades, amplify these cascades when acting with other mediators, and mediate molecular and cellular interactions (cross talk) between inflammation and thrombosis. Evidence from in vitro experiments, studies of experimental animals, and clinical observations in humans indicates that the PAF signaling system is important in sepsis and other syndromes of inflammatory injury and that therapeutic strategies to interrupt or terminate signaling via the PAF signaling system may be useful in these conditions.


Maternal Body Mass Index in Early Pregnancy and Risk of Epilepsy in Offspring.
There is growing concern about the long-term neurologic effects of prenatal exposure to maternal overweight and obesity. The causes of epilepsy are poorly understood and, in more than 60% of the patients, no definitive cause can be determined. To investigate the association between early pregnancy body mass index (BMI) and the risk of childhood epilepsy and examine associations between obesity-related pregnancy and neonatal complications and risks of childhood epilepsy. A population-based cohort study of 1 441 623 live single births at 22 or more completed gestational weeks in Sweden from January 1, 1997, to December 31, 2011, was conducted. The diagnosis of epilepsy as well as obesity-related pregnancy and neonatal complications were based on information from the Sweden Medical Birth Register and National Patient Register. Multivariate Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% CIs after adjusting for maternal age, country of origin, educational level, cohabitation with partner, height, smoking, maternal epilepsy, and year of delivery. Data analysis was conducted from June 1 to December 15, 2016. Risk of childhood epilepsy. Of the 1 421 551 children born between January 1, 1997, and December 31, 2011, with covariate information available, 7592 (0.5%) were diagnosed with epilepsy through December 31, 2012. Of these 3530 (46.5%) were female. The overall incidence of epilepsy in children aged 28 days to 16 years was 6.79 per 10 000 child-years. Compared with offspring of normal-weight mothers (BMI 18.5 to <25.0), adjusted HRs of epilepsy by maternal BMI categories were as follows: overweight (BMI 25.0 to <30.0), 1.11 (95% CI, 1.04-1.17); obesity grade I (BMI 30.0 to <35.0), 1.20 (95% CI, 1.10-1.31); obesity grade II (BMI 35.0 to <40.0), 1.30 (95% CI, 1.12-1.50); and obesity grade III (BMI≥40.0), 1.82 (95% CI, 1.46-2.26). The rates of epilepsy were considerably increased for children with malformations of the nervous system (adjusted HR, 46.4; 95% CI, 42.2-51.0), hypoxic ischemic encephalopathy (adjusted HR, 23.6; 95% CI, 20.6-27.1), and neonatal convulsions (adjusted HR, 33.5; 95% CI, 30.1-37.4). The rates of epilepsy were doubled among children with neonatal hypoglycemia (adjusted HR, 2.10; 95% CI, 1.90-2.33) and respiratory distress syndrome (adjusted HR, 2.43; 2.21-2.66), and neonatal jaundice was associated with more than a 50% increased risk of epilepsy (adjusted HR, 1.47; 95% CI, 1.33-1.63). The elevated risk of epilepsy in children of overweight or obese mothers was not explained by obesity-related pregnancy or neonatal complications. The rates of childhood epilepsy increased with maternal overweight or obesity in a dose-response manner. Given that overweight and obesity are modifiable, prevention of obesity may be an important public health strategy to reduce the incidence of childhood epilepsy.


[Experimental teratological studies on facial anomalies induced in mice by bis (dichloroacetyl) diamine. I. Establishment of an animal model of the median cleft face syndrome by the administration of bis (dichloroacetyl) diamine to mice].
Bis (dichloroacetyl) diamine (abbreviated as bisdiamine hereafter) was administered by oral intubation to pregnant Jcl: ICR and A/J mice at a dosage of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of gestation (VP = day 0). Fetuses were recovered at day 17.5 of gestation following maternal sacrifice. The numbers of resorptions, live fetuses and malformed fetuses were counted in the two strains of mice and the induced craniofacial anomalies were examined macroscopically and histopathologically. In both strains, median facial cleft, cleft palate, exencephalocele and open eyelids were commonly induced craniofacial anomalies. Bisdiamine-induced median facial cleft ranging in severity from minor midfacial disorganization to completely divided nose with a median cleft lip in Jcl: ICR and A/J was strikingly similar to a spectrum of midline defects of the median cleft face syndrome in humans. Histopathological examinations of severe median facial cleft in the two strains revealed that the bifurcated nasal septal cartilage showed irregular hypoplasia and that it was partly disorganized into several nodules of various shapes and sizes. These results indicate that bisdiamine treatment in mice provides a useful animal model of the median cleft face syndrome. Furthermore, higher frequency of median facial cleft and lower mortality in bisdiamine-treated Jcl: ICR indicate that bisdiamine treatment in Jcl: ICR is more effective than that in A/J to make an animal model of this syndrome.


Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart.
Inhibitory G protein activity (Gi) and nitric oxide (NO) modulate muscarinic-cholinergic (MC) inhibition of cardiac beta-adrenergic inotropic responses. We hypothesized that Gi mediates MC-NO synthase (NOS) signal transduction. Isoproterenol (0.2-0.8 microg/min) and acetylcholine (1 microM) were administered to isolated perfused rat hearts pretreated with saline (controls; n = 8) or pertussis toxin (PT; 30 microg/kg intraperitoneally 3 d before study; n = 20). PT abrogated in vitro ADP-ribosylation of Gi protein alpha subunit(s) indicating near-total decrease in Gi protein function. Isoproterenol increased peak +dP/dt in both control (peak isoproterenol effect: +2, 589+/-293 mmHg/s, P < 0.0001) and PT hearts (+3,879+/-474 mmHg/s, P < 0.0001). Acetylcholine reversed isoproterenol inotropy in controls (108+/-21% reduction of +dP/dt response, P = 0.001), but had no effect in PT hearts. In controls, NG-monomethyl-L-arginine (100 microM) reduced basal +dP/dt, augmented isoproterenol +dP/dt (peak effect: +4,634+/-690 mmHg/s, P < 0.0001), and reduced the MC inhibitory effect to 69+/-8% (P < 0.03 vs. baseline). L-arginine (100 M) had no effect in controls but in PT hearts decreased basal +dP/dt by 1, 426+/-456 mmHg/s (P < 0.005), downward-shifted the isoproterenol concentration-effect curve, and produced a small MC inhibitory effect (27+/-4% reduction, P < 0.05). This enhanced response to NO substrate was associated with increased NOS III protein abundance, and a three- to fivefold increase in in vitro calcium-dependent NOS activity. Neomycin (1 microM) inhibition of phospholipase C did not reverse L-arginine enhancement of MC inhibitory effects. These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels.


Transcriptome mining of RNA viruses (family Totiviridae ) in Eimeria necatrix and Eimeria stiedai.
Coccidian protozoa from the genus Eimeria are widespread parasites of vertebrates, causing serious disease (coccidiosis) and economic loss most notably in poultry. Several species of Eimeria are themselves infected with small RNA viruses assigned to the family Totiviridae . In this study, the sequences of two such viruses were newly determined, one of which represents the first complete protein-coding sequence of a virus from E. necatrix , an important pathogen of chickens, and the other of which is from E. stiedai , an important pathogen of rabbits. Sequence features of the newly identified viruses, compared with those of ones reported previously, provide several insights. Phylogenetic analyses suggest that these eimerian viruses constitute a well-demarcated clade, probably deserving of recognition as a distinct genus.


Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer.
Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N > 3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.


Mode of Delivery, Birth Characteristics, and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case-Control Study.
The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood. We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case-control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0-14 years; OR = 0.71, 95% CI: 0.51-0.99) and pediatric T-cell NHL (OR = 0.73, 95% CI: 0.55-0.97) compared with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57-0.93) or third or higher (OR = 0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared with first-borns. AYA (age 15-37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00-1.35). Associations between other birth characteristics, including plurality, maternal age, maternal education, and NHL risk, also exhibited variations across subgroups based on age of diagnosis and histologic subtype. These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL. This study underscores the etiologic heterogeneity of early-onset NHL.


Response of recalcitrant soil substances to reduced N deposition in a spruce forest soil: integrating laccase-encoding genes and lignin decomposition.
A long-term field experiment conducted in a Norway spruce forest at Solling, Central Germany, was used to verify and compare the response of lignin-decomposing fungal communities in soils receiving current and preindustrial atmospheric nitrogen (N) input for 14.5 years. Therefore, we investigated the decomposition of lignin compounds in relation to phenol oxidase activity and the diversity of basidiomycetes containing laccase genes in organic and mineral horizons. Lignin-derived CuO oxidation products and enzyme activity decreased with soil depth, while the degree of oxidative transformation of lignin increased. These patterns did not change with reduced atmospheric N input, likely reflecting a lasting saturation in available N. The laccase gene diversity decreased with soil depth in spring. In autumn, this pattern was only found in the control plot, receiving current N input. Principal component analysis confirmed the depth profile and distinguished a response of the fungal community to reduced N deposition for most organic layers in spring and a roof effect for the Oe layer in autumn. These responses of the fungal community did not translate into changes in enzyme activity and lignin content and decomposition, suggesting that transformation processes in soils are well buffered despite the rapid response of the microbial community to environmental factors.


Clinicopathological and prognostic significance of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) in malignant tumors: A meta-analysis.
Background: Accumulating studies have demonstrated that the expression of leucine-rich repeats and immunoglobulin-like domains protein1 (LRIG1) is associated with various types of tumors. However, the conclusions of previous studies are not completely consistent. Thus, we conducted this meta-analysis to further explore the authentic value of LRIG1 in cancer outcome and clinical significance. Methods: We systematically searched electronic databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database. The hazard ratios (HRs), odds ratio (OR) and 95 % confidence intervals (CI) were calculated for effect measures. Results: 16 qualified studies involving 2043 patients with cancer were enrolled. High LRIG1 expression was associated with a good prognosis in malignant tumors (HR: 0.49, 95% CI=0.39-0.59). Furthermore, positive expression rate of LRIG1 was distinctly lower in cancer tissues than that in normal tissues (OR: 0.09, 95% CI=0.05-0.17). Positive LRIG1 expression was definitely related with smaller tumor size (OR: 1.64, 95% CI=1.11-2.42), early tumor stage (OR: 3.67, 95% CI=1.87-7.21), well degree of differentiation (OR: 4.35, 95% CI=2.12-8.93) and negative recurrence (OR: 0.29, 95% CI=0.16-0.53). Conclusions: LRIG1 expression was associated with a good prognosis in terms of overall survival (OS) and might act as a predictive factor for characteristics of cancer patients.


A method for identifying mechanisms of neurologic injury from cardiac surgery.
A method for linking discrete surgical and perfusion-related processes of care with cerebral emboli, cerebral oxyhemoglobin desaturation, and hemodynamic changes may offer opportunities for reducing overall neurologic injury for patients undergoing cardiac surgery. An intensive intraoperative neurologic and physiologic monitoring approach was developed and implemented. Mechanisms likely to produce embolic (cerebral emboli), hypoperfusion (oxyhemoglobin desaturation), and hypotensive (hemodynamic changes) neurologic injuries were monitored and synchronized with the occurrence of surgical and perfusion clinical events/techniques using a case video. The system was tested among 32 cardiac surgery patients. Emboli were measured in the cerebral arteries and outflow of the cardiopulmonary bypass circuit among nearly 75% and 85% of patients, respectively. Oxyhemoglobin desaturation was measured among nearly 70% of patients. Hemodynamic information was recorded in 100% of patients. We developed and successfully implemented a method for detailed real-time associations between processes of clinical care and precursors of neurologic injury. Knowledge of this linkage will result in the redesign of clinical care to reduce a patient's risk of neurologic injury.


A Study of Siberia's Medicinal Plants Used in Homeopathy.
A current priority of national health care in Russia is to expand the range of drug substances, based on naturally occurring compounds, to use for treating socially significant diseases, such as cancer and cardiovascular diseases. The main objective of our study was to compile a contemporary list of Siberia's 'homeopathic plants', describing for each plant the corresponding therapeutic indications or main symptoms of disease. The textbook, Global Resources of Homeopathic Medicinal Raw Materials, was used to scrutinize the 709 species that are allowed for use in Russia, designating each of the 709 as either indigenous or non-indigenous to the region of Siberia. A homeopathic repertory, containing description of more than 1,800 single-component homeopathic medicines, was used to identify Siberia's medicinal plants used in homeopathy, along with the medical indications of each. The medicinal plants of Siberia used in homeopathy comprise 137 species of flowering plants, gymnosperms and sporophytes, belonging to 52 families. The most represented are the Compositae, Rosaceae, and Lamiaceae families. The inventory of Siberian plants has allowed us to identify the plants of this region used in homeopathy and will help to inform research on additional species with the potential for introduction into homeopathic practice.


[Surgical treatment of obstructive jaundice].
The analysis of results of the examination and surgical treatment of 567 patients with obstructive jaundice is presented. In 198 (34,9%) jaundice was caused by a cholelithic disease, in 362 cases (64.9%) there were tumoral lesions, in 7 (1,2%)- parasitogenic lesions of the organs of the hepatobiliopancreatoduodenal zone. The kinds of operations in obstructive jaundice are described with recommendations to create transvesicular hepatochlangiojejunoanastomosis in high blocks of bile tracts. Practical recommendations for the improved diagnosis of obstructive jaundice, its prevention and decreased postoperative lethality are given.


Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury.
Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.


Complementary food: international comparison on protein and energy requirement/intakes.
The possible role of early dietary habits as the origin of later consequences on health has raised questions on the optimal macronutrient intakes of the growing infant. Infants and toddlers in developed countries usually show a high dietary protein: energy ratio during the complementary feeding period, averaging 2.5-3, because of the protein density of solid weaning foods and the low percentage of mothers still breastfeeding beyond the first 6 months of life. In conditions of very high protein intakes, those in the higher classes of consumption seem to carry a higher risk of becoming obese later on. Over the limit of 14% energy from proteins in the 8- to 24- month period, some mechanisms may begin to operate leading young children towards an early adiposity rebound and overweight development. On the other hand, in many developing countries the only available weaning foods are cereals, with a low protein: energy ratio value. When the protein concentration of weaning foods falls below the limits of human milk (that is, from 1 g/100 kcal to lower levels), the infants' dietary requirements cannot be met. In planning interventions, the coverage of infants' dietary needs through all the various world regions should be considered together with the opportunity not to exceed higher limits.


Effects of adiposity on physical activity in childhood: Iowa Bone Development Study.
The aim of this study was to examine whether adiposity level is associated with subsequent physical activity (PA) level in childhood. Study participants were 326 children participating in the Iowa Bone Development Study. PA and fat mass were measured using accelerometers and dual-energy x-ray absorptiometry (DXA) at approximately 5, 8, and 11 yr. Data for relevant variables such as parents' education and PA levels and family income were also collected. Gender-specific generalized linear models were fit to examine the association between percentage body fat (%BF) at age 8 and intensity-weighted moderate- to vigorous-intensity PA (IW-MVPA) at age 11. After adjusting for IW-MVPA at age 8, the interval between the age 8 and 11 examinations, residualized change scores of %BF and IW-MVPA from age 5 to 8, and mother's education level, %BF at age 8 was negatively associated with IW-MVPA at age 11 among boys (P < 0.05). After adjusting for IW-MVPA at age 8, physical maturity, and family income, %BF at age 8 was negatively associated with IW-MVPA at age 11 among girls (P < 0.05). Categorical data analysis also showed that the odds ratio (OR) of being in the lowest quartile relative to the highest quartile of IW-MVPA at age 11 for boys and girls with high %BF at age 8 were approximately four times higher than the OR for those with low %BF at age 8 (OR = 4.38, 95% CI = 1.05-18.24 for boys; OR = 4.48, 95% CI = 1.35-14.85 for girls). This study suggests that adiposity level may be a determinant of PA behavior. Specific intervention strategies for overweight children may be needed to promote PA.


Reclaimed municipal wastewater for forage production.
This study aims to evaluate the possibility of using reclaimed municipal wastewater for agricultural purpose. We assessed the validity of municipal wastewater treatment, analyzing its chemical characteristics before and after the biological stabilization by pond treatment (WSP). The reclaimed municipal treated wastewater (TWW) was used to irrigate Cenchrus ciliaris. Experiments were carried out in greenhouse, from July 2013 to July 2014, comparing the effects of TWW with the water normally used for irrigation (tap water, TW) on the growth and flowering parameters of C. ciliaris. During this study, total coliforms, fecal coliforms, Escherichia coli, and Salmonella spp. were detected in TW, TWW, soils and plants under irrigation. Our results evidenced that TWW increased plant growth, producing taller plants with respect to TW. Total coliforms and fecal coliforms in TWW, TW, soils and plants were under the threshold recommended by the World Health Organization (WHO). Salmonella was never found in TW, TWW, or soil and plants irrigated with TWW. The absence of pathogens suggests that the pond treatment is an effective method to reclaim wastewater, lowering biochemical oxygen demand (BOD), chemical oxygen demand (COD) and pathogens. In this respect, TWW can be used as a valid alternative to freshwater for irrigation of fodder species.


Adolescents with gambling problems: from research to treatment.
Considerable interest in the area of youth gambling has prompted an increase in empirical investigations examining the correlates associated with youth experiencing severe gambling problems. Based upon the current state of knowledge and our clinical experience, the development of the treatment program for youth with serious gambling problems employed at the McGill University Youth Gambling Research and Treatment Clinic is described. The major tenets, underlying philosophy, and therapeutic processes are presented. A case study is included to illustrate the therapeutic approach. The authors present the need for greater funding for more basic and applied research and the necessity for further scientifically validated treatment and prevention programs.


Evidence for functional NK1-tachykinin receptors on motor neurones supplying the circular muscle of guinea-pig small and large intestine.
The guinea-pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)-insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum, 1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea-pig small intestine and on inhibitory motor neurones in the colon.


Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.
The purpose of these studies was to examine the growth characteristics and metastatic behavior of freshly isolated human colorectal carcinomas implanted into athymic nude mice. Four tumor lines were derived from primary colorectal carcinomas, three lines from hepatic metastases, and one line from a metastasis to a mesenteric lymph node. Subsequent to implantation into the subcutis or the muscularis, tumor lines derived from metastases grew faster in the nude mice than did cells isolated from the primary neoplasms. Regardless of the source of the cells, however, little or no visceral organ metastasis was found. Subsequent to i.v. injection, experimental lung colonies could be produced by some of the cells, but there was no correlation between lung tumor colony formation and the origin of the human colorectal cells. The intrasplenic injection of colorectal carcinoma cells provided a useful procedure to identify human colorectal carcinoma cells with metastatic potential to liver. Extensive tumor burdens in the liver were observed as early as 30 days after injection with two of the three liver metastasis-derived tumor lines. No liver metastases were found after the intrasplenic injection of cells isolated from the lymph node-derived tumor line. Ninety days after the intrasplenic injection of cells from the four primary colorectal carcinomas, limited liver metastases were observed. We conclude that metastasis of human colorectal carcinomas can be studied in nude mice, and its outcome depends upon both the intrinsic metastatic capacity of the human tumor cells and the organ environment of implantation.


Prevalence of leprosy in children of leprosy parents.
A cross sectional clinical study was done in slums and adjoining village of Raipur town. All the children in 100 families, in which at least one patient of proved leprosy was present were examined. Children of 100 non-leprosy families served as control. In leprous families prevalence was 14.2 times higher in comparison to children in control group. Also prevalence was higher in children of those families in which number of patients were more than one, or there was lepromatous leprosy. In children the common type of lesion were tuberculoid, indeterminate, borderline and pure neural type in that order, while no case of lepromatous leprosy was seen.


Effect of doxycycline on transforming growth factor-beta-1-induced matrix metalloproteinase 2 expression, migration, and collagen contraction in nasal polyp-derived fibroblasts.
It is well known that doxycycline has antibacterial and anti-inflammatory effects. In this study, we aimed to investigate the effects of doxycycline on the transforming growth factor (TGF) beta 1-induced matrix metalloproteinase (MMP) 2 expression, migration, and collagen contraction, and to determine its molecular mechanism on nasal polyp-derived fibroblasts (NPDF). NPDFs were isolated from the nasal polyps of six patients. Doxycycline was used to pretreat TGF-beta-1-induced NPDFs and ex vivo organ cultures of nasal polyps. Cytotoxicity was evaluated by using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Smad2/3 is one of the major transcription factors of TGF-beta signaling. The expression levels of MMP2 and Smad2/3 were measured by using Western blotting, reverse transcription-polymerase chain reaction, and immunofluorescence staining. The enzymic activity of MMP2 was analyzed by using gelatin zymography. Fibroblast migration was evaluated by using transwell migration assays. Contractile activity was measured by a collagen gel contraction assay. The expression level of MMP2 in nasal polyp tissues increased in comparison with inferior turbinate tissues. TGF-beta-1-induced NPDFs were not affected by doxycycline (0-40 μg/mL). The expression levels of MMP2 and activation of Smad2/3 in TGF-beta-1-induced NPDFs and in organ cultures of nasal polyps were significantly downregulated with doxycycline pretreatment. Doxycycline also reduced TGF-beta-1-induced fibroblast migration and collagen contraction in NPDFs. Doxycycline inhibited TGF-beta-1-induced MMP2 expression, migration, and collagen contraction via the Smad2/3 signal pathways in NPDFs.