Analytical evaluation of a high-throughput enzyme-linked immunosorbent assay for acrylamide determination in fried foods.
The analytical performance and evaluation of a kit-based ELISA for the determination of acrylamide in fried potato and corn chip samples are described. The sample homogenate is subjected to clean-up using SPE, followed by analyte derivatization and ELISA detection. Accuracy, precision and linearity of the ELISA procedure have been validated using spiked samples. Analytical recovery ranged from 91.8% to 96.0% with coefficients of variation below 15%. Good linearity over a wide range of dilution and minimal assay drift was observed within a microtiter plate. IC50 value of the calibration curve was 110 ng/mL, with the limit of detection about 5 ng/mL and dynamic range from 10 to 1000 ng/mL. The high specificity of the ELISA was demonstrated by cross-reactivity study using 11 potential cross-reactants. A good correlation between the results obtained from the ELISA and GC-MS within the concentration range 120-1500 μg/kg was found in the chip samples (r=0.992, n=120). The data demonstrate that the evaluated and validated ELISA has a potential utility in a quick, simple and reliable acrylamide screening analysis for the medium- and large-sized food companies, as well as for residue laboratories and the food industry dealing with improving the chemical safety of foods available to the consumer.


Outcome of drug abuse in a 20-year follow-up study of drug-experimenting schoolchildren in Finland.
The fate of 119 drug-experimenting schoolchildren who had been interrogated by the narcotics police of Helsinki, Finland, during 1 year, 1971-72, was studied 20 years later. The material was divided in two groups: those with a favourable outcome (n=49) and those with a poor outcome (n=70). Nineteen had died. Criteria for poor outcome were death, prison sentence, psychiatric hospitalization, or continuation of crimes. The group with a favourable outcome was alive, did not have prison sentences or psychiatric hospitalizations, and had not been caught by the police after the initial phase of the study. Offences against property in early adolescence and intravenous drug use were predictive factors for imprisonment, psychiatric hospitalization, and death. A poor atmosphere at home and the occupation of the father as labourer were predictive factors for imprisonment, psychiatric hospitalization, and death for boys. For girls low education was predictive of imprisonment and psychiatric hospitalization. Drug use in adolescence is a signal of greater risk for adjustment problems in later life.


Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.
To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of 539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLE disease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.


Prognostic value of preoperative controlling nutritional status in patients with glioblastoma.
Accumulating evidence has demonstrated a correlation of preoperative controlling nutritional status (CONUT) score with prognosis in several malignancies, but only few studies have explored the influence of preoperative COUNT score in glioblastoma multiforme (GBM). Therefore, this study aimed to validate the connection between the clinical outcome of patients with GBM and the preoperative CONUT score. This study retrospectively evaluated the preoperative CONUT scores of 94 patients with GBM undergoing surgery between December 2015 and May 2018. The cutoff value of the CONUT score was determined using the X-tilesoftware. The influence of preoperative CONUT score on overall survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard regression model. The optimal preoperative CONUT score cutoff level was 4, and patients were divided into either low-CONUT score (<4, n = 78, 82.98 %) or high-CONUT score (≥4, n = 16, 17.02 %) groups. After univariate analysis, high-CONUT scores were closely associated with decreased overall survival (hazard ratio [HR]: 2.581, 95 % confidence interval [CI]: 1.475-4.516, p = 0.001). After multivariate analysis, this relationship continued to remain significant (HR: 3.110, 95 % CI: 1.724-5.611, p < 0.001). Current research indicates that the preoperative CONUT score has potential application as a predictor of prognosis in patients with GBM. Thus, it is important that patients with GBM undergo perioperative nutrition interventions according to their CONUT scores, which would be an effective treatment plan to improve their survival and prognosis.


The congenital undescended scapula syndrome: Sprengel and the cleithrum: a case series and hypothesis.
Sprengel deformity is a rare congenital shoulder girdle anomaly characterized by scapula malposition, periscapular muscle atrophy, and limited shoulder movement. Traditionally, it has been managed by omovertebral bar excision and muscle transplantation procedures guided by age and Cavendish grade. We present a unique observation in humans: a case series with Sprengel deformity possessing a cleithrum, an ancestral remnant of shoulder girdle development found in archaic bony fish. Nine patients presented with so-called Sprengel deformity to a tertiary referral shoulder clinic. All were assessed clinically and radiologically with scapular radiographs and computed tomography or magnetic resonance imaging scans. The clinical and radiologic features were classified according to Cavendish and Rigault systems, respectively, and the scapular ratio was assessed. All patients were assigned grade 4 on the Cavendish scale. Six were grade 2 and 3 were grade 3 on the Rigault scale. The distinguishing pathoanatomic feature was partial endomuscular ossification of medial scapular suspension muscles, analogous to the cleithrum of bony fish. Five cases were treated operatively and 4 nonoperatively. Mean elevation and abduction significantly improved in surgical cases. This finding not only challenges classic management of these rare patients but offers insight into scapular embryology and development. The association of scapular developmental and urogenital anomalies suggests that screening of the renal tract and genetic investigation in those with undescended scapula syndrome be considered. We suggest, to emphasize the nature of incomplete scapular descent and associated congenital anomalies and to clarify imprecise common use of the term Sprengel deformity, that this condition be called the congenital undescended scapula syndrome.


Shedding light on current trends in molecular optogenetics.
Molecular optogenetics is a highly dynamic research field. In the past two years, the field was characterized by the development of new allosteric switches as well as the forward integration of optogenetics research towards application. Further, two areas of research have significantly gathered momentum, the use of optogenetics to control liquid-liquid phase separation as well as the application of optogenetic tools in the extracellular space. Here, we review these areas and discuss future directions.


Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering.
The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 μm (±48.8 μm), whereas in the edematous lung, it was 1040 μm (±90 μm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = -0.9542, p < 0.0117) and sponge phantom (r = -0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma.


Co-disposal of municipal solid waste incineration fly ash and bottom slag: A novel method of low temperature melting treatment.
Conventional melting for disposing municipal solid waste incineration (MSWI) fly ash or bottom slag needed high temperature and consumed high energy. High calcium content in fly ash and high silicon content in bottom slag brought them high melting point, respectively. Based on the analysis of chemical composition and phase diagram, suitable contents, namely 30%-40% CaO, 45%-60% SiO2 and 10%-15% Al2O3, were proposed to obtain a lower-melting-point mixture system. When the mass ratio of fly ash to bottom slag was 1:5, lowest melting point can be obtained. It was 1,190 ℃, lower than that of fly ash (1,448 ℃) and bottom slag (1,310 ℃). The toxicity characteristic leaching procedure of slags obtained from low melting treatment met the leaching toxicity of Chinese standard GB 5085.3-2007, and the slags containing about 25 wt% CaO, 10 wt% Al2O3 and 45 wt% SiO2 can be used for preparing CaO-Al2O3-SiO2 glass ceramics. The co-process of fly ash and bottom slag realized the low temperature melting treatment with low energy consumption.


Gonadal receptors. I. Evidence for irreversibility in the binding of human chorionic gonadotropin and human luteinizing hormone.
The binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors of rat testes has generally been assumed to follow an equilibrium model similar to that proposed for many enzyme systems. Our work shows that equilibrium dissociation constant (Kd) and number of hormone binding sites (Bmax) are highly sensitive to changes in hormone and/or receptor concentration and to treatment received by tissue or receptor preparation prior to the assay. The results of binding assays obtained using receptor preparation pretreated with hormone (labeled as well as unlabeled) indicated that the binding reaction between hormone and receptor was irreversible and that pretreatment of the tissue with hormone greatly alters the number of high affinity gonadotropin binding sites in the testicular homogenate. Data from studies involving increasing receptor concentrations revealed that increasing the mass of particulate receptors in the binding assays leads to higher Kd as well as Bmax values. These findings are incompatible with a binding model based upon occupancy of receptor sites and the state of equilibrium implied. The incompatibilities are analyzed and an alternate model advanced (Bhalla, V.K., Trowbridge, C.G., Chen, C.J.H., Lindeman, J.G. and Rojas, F.J. (1979) Biochim. Biophys. Acta 584, 436--453).


Paediatric Rapid Response Systems: a literature review.
Paediatric cardiorespiratory arrest carries a poor prognosis. The most common cause is respiratory insufficiency or hypotension/shock, which can be reversible. The use of RRSs in adult hospitals that proactively intervene when signs of physiological instability occur is widespread and increasing although the level of evidence for their efficiency is a matter of debate. A systematic literature review was undertaken to evaluate and summarise the current knowledge about paediatric RRSs. Paediatric RRSs are in use in several places around the world. One study shows a statistically significant decrease in mortality rate after implementation. Two studies show a non-significant association with decreased mortality rate. Cardiac and/or respiratory arrest rates decreased in all four before-after studies with statistical significance in two. Cardiac arrest and death are rare in paediatric hospitals, which can in part explain the difficulties to demonstrate statistically significant benefits. There are also specific problems regarding calling criteria due to age related physiological diversity as well as chronic disease.


The effect of bicycling on PSA levels: a systematic review and meta-analysis.
Recent literature has suggested that bicycling may be associated with increases in serum PSA levels, a diagnostic and prognostic marker for prostate cancer. To further investigate this relationship, we conducted a systematic review and meta-analysis of current literature in this field. MEDLINE, CENTRAL, CINAHL and SPORTDiscus were searched using MeSH terms and keywords for English publications related to bicycle riding and PSA. Studies were included if PSA was measured relative to cycling activity in healthy men who were free of any prostatic condition. Case studies were excluded. Eight studies met our inclusion criteria, comprising 912 participants that engaged in, or self-reported, bicycling activity. Six studies investigated the acute pre-post change in PSA following bicycling activity that ranged from a single cycling bout of 15 min to a 4-day cycling event. Following cycling activity, two studies reported total PSA increased from baseline by up to 3.3-fold, free PSA increased in one study by 0.08±0.18 ng ml(-)(1) and did not change in four studies. One study compared PSA in elite/professional cyclists versus non-cyclists and demonstrated no significant difference in PSA measurements between groups. Data from six studies were meta-analyzed and demonstrated no significant increase in PSA associated with cycling from pre to post (mean change +0.027 ng ml(-)(1), s.e.m.=0.08, P=0.74, 95% confidence interval (CI)=-0.17-0.23). Our findings suggest that there is no effect of cycling on PSA; however, the limited number of trials and the absence of randomized controlled trials limit the interpretation of our results. Additionally, the median sample size only consisted of 42 subjects. Therefore, our study may have low statistical power to detect a difference in PSA. Although, a higher sample size may demonstrate statistical significance, it may not be clinically significant. Studies of higher empirical quality are needed.


Morphological characterization of the antennal sensilla of t he earwig Anisolabis maritima (Dermaptera: Carcinophoridae) with reference to their probable functions.
The earwig, Anisolabis maritima (Dermaptera: Carcinophoridae), is one of the most significant insects in KSA because, it was recorded in Saudi Arabia as a beneficial predator on eggs and newly hatched larvae of the red palm weevil, Rhyncophorus ferrugineus. We examined the external morphology of the antennal sensilla of males and females of A. maritima using scanning electron microscopy (SEM). The filiform antennae of A. maritima were of the conventional type comprising a basal scape, pedicle and a long, thread-like flagellum, which was composed of 12 flagellomeres of males and 16 flagellomeres of females. Six morphologically unique sensillar types were found and described on the antennae of males and females of A. maritima. Of those identified, there were three types of porous trichoid sensilla (long, curved and arcuate), and two types of basiconic sensilla (short and curved), and one type of aporous trichoid sensilla. The shape, external morphology and array of sensilla on the antennae of males and females of A. maritima were similar.


The vigor of drug treatment in the control of hypertension: results from the Munich Blood Pressure Study.
The strength of antihypertensive drug treatment was investigated in a representative sample of the population of Munich. The Munich Blood Pressure Study, a cross-sectional study (MBS I) with follow-up one year later (MBS II) of a random sample of 3,198 citizens aged 30-69 years (response rate 69.3 percent) served as the data base. Using an empirical scale of the relative potency of antihypertensive drugs, the vigor of drug therapy was estimated. One unit of vigor was defined as the equivalent of the recommended average daily dose of the specific drug for long-term treatment. This index of therapeutic vigor was then applied to two groups, treated but uncontrolled hypertensives and controlled hypertensives. We found that 85 percent of the treated uncontrolled hypertensives and 90 percent of those with controlled hypertension were taking only small amounts of medication (less than two units of vigor). Particularly striking was the result that approximately 50 percent of each group received less than one unit of vigor. Based on these data it is concluded that physicians failed to prescribe adequate doses of antihypertensive agents for uncontrolled hypertensives. Furthermore, since a large number of patients had their blood pressure controlled by only very small doses of antihypertensive agents, it may be assumed that at least some of them did not require drug treatment or could have their blood pressure controlled by nonpharmacologic measures alone.


Human Z alpha 1-antitrypsin accumulates intracellularly and stimulates lysosomal activity when synthesised in the Xenopus oocyte.
Microinjection of human liver mRNA from a patient homozygous for alpha 1-antitrypsin deficiency (PiZZ) into Xenopus oocytes led to a 2--10-fold increase in lysosomal activity. Stimulation of lysosomal activity was not observed when mRNA from a normal human liver (alpha 1-antitrypsin PiMM), or water was injected into the oocyte. This lysosomal activity was oocyte derived and was not due to translation products of the human liver mRNA. Thus a protein that accumulates intracellularly in the secretory pathway is capable of stimulating lysosomal activity.


Non-contact monitoring of the depth temperature profile for medical laser scanning technologies.
Medical treatments such as high-intensity focused ultrasound, hyperthermic laser lipolysis or radiofrequency are employed as a minimally invasive alternatives for targeted tissue therapies. The increased temperature of the tissue triggers various thermal effects and leads to an unavoidable damage. As targeted tissues are generally located below the surface, various approaches are utilized to prevent skin layers from overheating and irreparable thermal damages. These procedures are often accompanied by cooling systems and protective layers accounting for a non-trivial detection of the subsurface temperature peak. Here, we show a temperature peak estimation method based on infrared thermography recording of the surface temperature evolution coupled with a thermal-diffusion-based model and a time-dependent data matching algorithm. The performance of the newly developed method was further showcased by employing hyperthermic laser lipolysis on an ex-vivo porcine fat tissue. Deviations of the estimated peak temperature remained below 1 °C, as validated by simultaneous measurement of depth temperature field within the tissue. Reconstruction of the depth profile shows a good reproducibility of the real temperature distribution with a small deviation of the peak temperature position. A thermal camera in combination with the time-dependent matching bears the scope for non-contact monitoring of the depth temperature profile as fast as 30 s. The latest demand for miniaturization of thermal cameras provides the possibility to embed the model in portable thermal scanners or medical laser technologies for improving safety and efficiency.


Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.
To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.


Pin vs plate fixation for metacarpal fractures: a meta-analysis.
The differences in the clinical and functional outcomes of closed reduction and percutaneous pin fixation and open reduction with internal fixation (ORIF) using plate and screws have been systematically synthesized by one meta-analysis. With newer studies being published, an effort to update the earlier meta-analysis is necessary. Comprehensive searches were done systematically through PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases. Randomized controlled trials, quasi-experimental studies, prospective comparative non-randomized studies, and even studies reporting findings from retrospective chart review were eligible to be included. Statistical analysis was done using STATA version 13.0. GRADE assessment was done to assess the quality of pooled evidence. A total of 9 studies were included. The pooled estimates did not suggest any significant differences in the disabilities of the arm, shoulder, and hand (DASH) score [WMD - 0.77; 95% CI, - 3.55, 2.00; I2 = 75.5%], range of movement (ROM) of the metacarpophalangeal joint (o) [WMD 4.44; 95% CI, - 4.19, 13.07; I2 = 86.0%], and grip strength [WMD - 4.63; 95% CI, - 14.52, 5.26; I2 = 86.9%] among the two intervention modalities. No difference was seen in the risk of complications between the two interventions (RR 0.93; 95% CI, 0.57, 1.53; I2 = 31.2%). For all the outcomes, the quality of pooled evidence was judged as low to very low. No significant long-term differences were noted in the functional outcomes suggesting that both these techniques are comparable. The choice of modality should be made based on the skills and preference of the surgeon and availability of resources.


Impact of exercise training on redox signaling in cardiovascular diseases.
Reactive oxygen and nitrogen species regulate a wide array of signaling pathways that governs cardiovascular physiology. However, oxidant stress resulting from disrupted redox signaling has an adverse impact on the pathogenesis and progression of cardiovascular diseases. In this review, we address how redox signaling and oxidant stress affect the pathophysiology of cardiovascular diseases such as ischemia-reperfusion injury, hypertension and heart failure. We also summarize the benefits of exercise training in tackling the hyperactivation of cellular oxidases and mitochondrial dysfunction seen in cardiovascular diseases.


[A new actograph operating by capacitance sensing].
Capacitance sensing devices are useful for ecological and ethological studies (Zucker et al., 1968). If the location and activity of small animals (e.g. newts) is to be recorded, problems arise due to the very small changes in capacitance that must be detected reliably. By using a special bridge circuit (Fig. 2) an extremely sensitive detector can be constructed. With the output voltage and frequency of the RF-generator kept constant, the RF-current is determined only by the capacitance of the two sensors C1 and C2. This current is rectified by the transistors T1 and T2 and the difference is detected by a Schmitt trigger. Outside influences that affect both sensors in the same way will thus be eliminated, resulting in excellent long-time stability and sensitivity of the device.The sensors simply consist of copper foils, about 1 cm apart, glued onto an insulating, flat surface. A glass with the animal is placed on these sesors and no further connection is necessary. The change in capacitance is generated by the animals building a capacitance bridge over the space between the foils. By a suitable arrangement of foils and spaces (Fig. 3), any desired information can be obtained concerning activity, time of entering and leaving the hiding place, etc.Newts and salamanders need a damp atmosphere. It was found that a moist paper on the bottom of the container will increase the sensitivity if its degree of humidity be kept constant.


Candida thrombosis of the innominate vein with septic pulmonary emboli.
Thrombosis of central veins has become more prevalent because of increased use of long-term central venous catheterization. Candida superinfection of the thrombus can occur particularly in patients on long-term antibiotic therapy and on parenteral nutrition. Removal of the catheter, thrombolytic therapy, anticoagulation, and antifungal therapy with amphotericin B will usually eradicate the candidemia and restore venous patency. Occasionally this therapeutic regimen fails. This case report illustrates such a failure in which multiple pulmonary emboli could have caused death. Surgical thrombectomy of the innominate vein effectively removed the source of the Candida sepsis and maintained patency of a major vein. Thrombectomy should be considered as a therapeutic option in septic central vein thrombosis.


Job satisfaction and depression in the Spanish Society of Periodontology and Research (SEPA) members, and their relation to the burnout syndrome. Creation of a structural model.
This study is aimed at getting to know the existing relationship between the dimensions of the burnout syndrome and job satisfaction, on one hand, and depressive feelings on the other through the creation of a structural model aimed at relating all these concepts on a sample of Spanish periodontists. The initial sample comprised 284 individuals, who represented 20% of the members of the Spanish Society of Periodontology and Research (www.SEPA.es). These individuals were chosen randomly by means of stratified sampling with proportional affixation by their autonomous community of residence. All participants were sent by post the MBI, CET and job-satisfaction questionnaires. The software package used for data analysis was LISREL v. 8.7 by checking models of structural equations so as to prove the proposed model's adjustment. The total number of answered questionnaires was 170 (59.85%). A positive relation was observed between emotional tiredness and depersonalization and depression. However, this dimension correlated negatively with job satisfaction and self-realization. The obtained results show that, in this sample of periodontists, job satisfaction acts as a modulator in the transition from emotional tiredness to depression.


[Pathoanatomical preparation and reporting for dysplasias and cancers of the cervix uteri: cervical biopsy, conization, radical hysterectomy and exenteration].
A careful macroscopic description with selection of representative tissue for histological examination is required for quality assurance, for assessing prognostic factors and for answering legal questions in (pre)cancerous lesions of the cervix uteri. Exact and standardized gross inspection and preparation are decisive for the quality of the histopathological statement. The extent of cervical carcinomas should be given in three dimensions, including the relative depth of invasion into the cervical wall. The report should include size, type (according to the WHO classification) and grading of the tumor, the presence of lymphatic as well as blood vessel invasion and perineural involvement. The statement for resection margins should include the vaginal, parametrial, rectal and vesical directions. It is also mandatory to document the number of lymph nodes with metastatic disease in relation to the total number of nodes investigated. The staging should follow the TNM system. In the handling of conisation specimens, it is important to appropriately document localization, horizontal expansion, depth of invasion including microinvasion of any dysplastic or malignant lesions. Clockwise dissection of the conisation specimen, total submission, and step sections are recommended. The preparation of exenteration specimens is a highly skilled job: the exact tumor dimension should be given in its relation to all resected organs and structures with special focus on resection margins.


Differential effect of polysaccharide and nonpolysaccharide components in Sijunzi decoction on spleen deficiency syndrome and their mechanisms.
Sijunzi decoction (SJZD), reported in "Tai Ping Hui Min He Ji Ju Fang" of the Song dynasty, is the basic prescription for the treatment of spleen deficiency syndrome (SDS) in traditional Chinese medicine (TCM). It is composed of Ginseng Radix et Rhizoma, Atractylodisa Macricephalae Rhizoma, Poria and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. This study sought to explore the effects of different components in SJZD (including nonpolysaccharide NPS and active polysaccharide S-3) on SDS rats and their underlying mechanisms. First, SDS model rats were established by reserpine injection and then treated with SJZD, NPS and S-3. To clarify their effect on GI motility and immune function, the gastrointestinal (GI) hormone levels in rat serum and their related receptor expressions in rat intestine were detected by enzyme-linked immunosorbent assay (ELISA) and western blot, and the intestinal T lymphocyte expression were quantified by flow cytometry. The levels of SCFAs in feces and serum were measured by gas chromatography-mass spectrometry (GC-MS), and the gut microbiota composition was determined by 16S RNA sequencing. Furthermore, pseudo-germ-free (pGF) and gut microbiota dysbiosis (GMD) model rats were established to verify the key role of the gut microbiota in the treatment of SDS with SJZD, NPS and S-3. SJZD has a stronger therapeutic effect on intestinal immune and GI hormone secretion in SDS rats, while the efficacy of NPS and S-3 showed slight differences. NPS mainly regulated the secretion of GI hormones in SDS rats and directly improved intestinal immunity by increasing the expression of T lymphocyte cells, while S-3 mainly enhanced intestinal immune function by increasing the expression of T lymphocyte cells and repairing the intestinal barrier in both direct and indirect ways. Additionally, experiments in pGF and GMD rats have proven that the immune-enhancing effects of SJZD, NPS, and S-3 on SDS rats and the regulation of GI hormones of S-3 are related to modulation of the gut microbiota composition, while the regulation of GI hormones by SJZD and NPS is not completely dependent on this modulation. In particular, Lactobacillus, SMB53, Blautia, Dorea, Collinsella and Adlercreutzia were significantly modulated by SJZD, and 3 genera (including Lactobacillus, Dorea and SMB53) were also remarkably regulated by NPS. S-3 significantly increased the abundance of Butyricimonas and Collinsella, which were different from altered genera in the SJZD group. This study uncovered that NPS and S-3 are inseparable effective substances for SJZD in the treatment of SDS rats, in which NPS mainly improves intestinal motility dysfunction and S-3 mainly enhances intestinal immunity. The mediation effect of the gut microbiota is extremely important, but the regulating effect of NPS on gastrointestinal hormones has nothing to do with the gut microbiota.


Nucleic acid fluorochromes and flow cytometry prove useful in assessing the effect of chlorination on drinking water bacteria.
Flow cytometry (FCM), combined with staining using two fluorochromes (propidium iodide, PI, or SYBR Green II RNA gel stain, SYBR-II), was used to assess nucleic acid injuries to chlorinated drinking water bacteria. Highly fluorescent SYBR-II-stained bacteria were converted to bacteria with low fluorescence after chlorination. PI staining of bacteria exposed to different doses of chlorine showed membrane permeabilisation ([Cl2] < 0.2 mg L(-1)) and nucleic acid damage at higher doses ([Cl2] > 0.3 mg L(-1)). Above a threshold dose (between 1.5 and 3 mg Cl2 L(-1)), nucleic acids appeared severely damaged and incapable of being stained by PI or SYBR-II. These results constitute evidence that FCM is a promising tool for assessing drinking water bacteria injuries and for controlling chlorine disinfection efficiency much more rapidly than the standard sensitive but time-consuming heterotrophic plate count method.


Percutaneous renal calculus removal in an extracorporeal shock wave lithotripsy practice.
The introduction of extracorporeal shock wave lithotripsy and transurethral ureteroscopy have altered markedly the incidence of standard surgical and percutaneous stone removal procedures. To help define the present role of percutaneous procedures in our practice we evaluated our indications, results and the clinical course of 143 patients who were treated primarily with percutaneous methods during 1 year in which extracorporeal shock wave lithotripsy also was available. The complexity of these residual percutaneous cases necessitated repeat endoscopic or fluoroscopic stone removal procedures in 20 per cent and ancillary extracorporeal shock wave lithotripsy in 22 per cent, and led to a slightly higher complication rate than in our previous percutaneous series. Despite the effectiveness of extracorporeal shock wave lithotripsy, percutaneous methods still are necessary for comprehensive therapy of upper tract urolithiasis.


Gastrointestinal hemorrhage associated with chronic mesenteric venous occlusion.
Chronic mesenteric venous thrombosis without involvement of the splenic or portal veins may lead to gastrointestinal hemorrhage from mesenteric varices. Three cases are presented in this report; 1 patient died secondary to blood loss and 2 patients have experienced a benign clinical course. The presentation, methods of diagnosis, and therapeutic options for this disorder are described.


IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes.
Interleukin-17 (IL-17) is a proinflammatory cytokine that is expressed in the synovium T cells of rheumatoid arthritis (RA). This cytokine is implicated in the inflammation and destruction of the joint. However, the role of IL-17 on the production of vascular endothelial factor (VEGF) important to synovial proliferation has still not been identified. In this study, we investigated the effect on cultured rheumatoid fibroblast-like synoviocytes (FLS) of the IL-17 on the production and expression of VEGF, which play an important role in angiogenesis in rheumatoid synovium. IL-17 increased the production of VEGF dose dependently and the mRNA expression of VEGF. These results suggest that IL-17 might influence angiogenesis in RA by up-regulating the expression of VEGF in rheumatoid FLS.


Hypoxia-induced circADAMTS6 in a TDP43-dependent manner accelerates glioblastoma progression via ANXA2/ NF-κB pathway.
Circular RNAs (circRNAs) play important roles in the malignant progression of tumours. Herein, we identified an unreported circRNA (hsa-circ-0072688, also named circADAMTS6) that is specifically upregulated in the hypoxic microenvironment of glioblastoma and closely correlated with poor prognosis of gliblastoma patients. We found that circADAMTS6 promotes the malignant progression of glioblastoma by promoting cell proliferation and inhibiting apoptosis. Mechanistically, the hypoxic tumour microenvironment upregulates circADAMTS6 expression through transcription factor activator protein 1 (AP-1) and RNA-binding protein TAR DNA-binding protein 43 (TDP43). Moreover, circADAMTS6 accelerates glioblastoma progression by recruiting and stabilising annexin A2 (ANXA2) in a proteasomes-dependent manner. Furthermore, we found T-5224 (AP-1 inhibitor) treatment induces downregulation of circADAMTS6 and then inhibits tumour growth. In conclusion, our findings highlight the important role of the circADAMTS6/ANXA2 axis based on hypoxic microenvironment in glioblastoma progression, as well as its regulation in NF-κB pathway. Targeting circADAMTS6 is thus expected to become a novel therapeutic strategy for glioblastoma.


Historical roots of the field of learning disabilities: some nineteenth-century German contributions.
The field of learning disabilities is often thought of as having come into being in the early 1960s. In reality, there is a long history of scientific investigation into psycho-anatomic functions. This article highlights the scientific contributions of some major nineteenth-century German researchers, their astounding attempts at describing neuropsychologic dysfunction, and their struggle to conceptionalize and cerebrally localize the clinical syndromes they had observed. After Pierre Paul Broca's discovery of "motor aphasia," Carl Wernicke described the clinical syndrome of "sensory aphasia" and its cerebral localization in 1871. Wernicke's investigation was at the onset of rapidly accumulating insights into the complexities of neuropsychologic functions as they were investigated by researchers such as Ludwig Lichtheim, Hugo Karl Liepmann, B. Berlin, Hubert Grashey, and J. K. Goldscheider. The long-term influence of this research on the development of the field of learning disabilities is discussed.


Effects of gene-augmentation on the formation, characteristics and microbial community of 2,4-dichlorophenoxyacetic acid degrading aerobic microbial granules.
Development of 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granular sludge was conducted in two sequencing batch reactors (SBR) with one bioaugmented with a plasmid pJP4 donor strain Pseudomonas putida SM1443 and the other as a control. Half-matured aerobic granules pre-grown on glucose were used as the starting seeds and a two-stage operation strategy was applied. Granules capable of utilizing 2,4-D (about 500 mg/L) as the sole carbon source was successfully cultivated in both reactors. Gene-augmentation resulted in the enhancement of 2,4-D degradation rates by the percentage of 65-135% for the granules on Day 18, and 6-24% for the granules on Day 105. Transconjugants receiving plasmid pJP4 were established in the granule microbial community after bioaugmentation and persisted till the end of operation. Compared with the control granules, the granules in the bioaugmented reactor demonstrated a better settling ability, larger size, more abundant microbial diversity and stronger tolerance to 2,4-D. The finally obtained granules in the bioaugmented and control reactor had a granule size of around 600 μm and 500 μm, a Shannon-Weaver diversity index (H) of 0.96 and 0.55, respectively. A shift in microbial community was found during the granulation process.


Novel determination of polychlorinated naphthalenes in water by liquid chromatography-mass spectrometry with atmospheric pressure photoionization.
This study presents the development, optimization, and validation of a novel method for the determination of polychlorinated naphthalenes (PCNs) by liquid chromatography-atmospheric pressure photoionization (APPI), using toluene as dopant. The mass spectra of PCN 52, 54, 66, 67, 73, and 75 were recorded in negative ionization. The base ions corresponded to [M-Cl+O](-), where M is the analyte molecule. A strategy, which includes designs of experiments, for the development, the evaluation, and the optimization of the LC-APPI-MS/MS methods is also described. Finally, a highly sensitive method with low instrumental limits of detection (LoDs), ranging from 0.8 pg for PCN 75 to 16 pg for PCN 54 on column, was validated. A Thermo Hypersil Green PAH (100 mm × 2.1 mm, 3 μm) column was used with acetonitrile/water/methanol as mobile phase. The method was applied for the determination of the selected PCNs in surface and tap water samples. A simple liquid-liquid extraction method for the extraction of PCNs from water samples was used. Method LoQs ranged from 29 ng L(-1), for PCN 73, to 63 ng L(-1), for PCN 54, and the recoveries ranged from 97 to 99%, for all congeners. This is the first LC-APPI-MS/MS method for the determination of PCNs in water samples.


Direct accessory optic projections to the vestibulo-cerebellum: a possible channel for oculomotor control systems.
The nucleus of the basal optic root (nBOR) receives direct retinal projections in all classes of vertebrates. This nucleus is also known as the medial terminal nucleus of the accessory optic tract, or as the nucleus extomamillaris. Following a series of HRP injections into the uvula and flocculonodular lobe of pigeons, both large and small cells of the nBOR were labelled bilaterally with the marker. No significant transport of HRP to nBOR was observed following injections of more rostral folia of the posterior or anterior lobes of the cerebellum. In view of the prominence of the tract from retina to nBOR and the presence of a monosynaptic pathway from nBOR directly to the vestibulo-cerebellum, we suggest this bisynaptic, "lemniscal", retino-cerebellar channel may be the substrate by which visual stimuli directly trigger oculomotor responses mediated by the vestibulo-cerebellum.


Transplanted human induced pluripotent stem cells- derived retinal ganglion cells embed within mouse retinas and are electrophysiologically functional.
Glaucoma is an optic neuropathy characterized by permanent visual field loss caused by the death of retinal ganglion cells (RGCs) and it is the leading cause of irreversible blindness worldwide. Consequently, there is an unmet need for the development of new strategies for its treatment. We investigated RGC replacement therapy as a treatment for ganglion cell loss. Human-induced pluripotent stem cells (hiPSCs) were differentiated into mature, functional RGCs in vitro, labeled with AAV2.7m8-SNCG-eGFP, and transplanted intravitreally in wild-type 4-month-old C57BL/6J mice. Survival of the transplanted hiPSC-RGCs was assessed by color fundus photography and histological studies confirmed the localization of the transplanted hiPSC-RGCs within the retina. Two-photon live imaging of retinal explants and electrophysiological studies confirmed that the morphology and function of the transplanted hiPSC-RGCs were similar to native RGCs. These experiments will provide key strategies to enhance the efficiency of stem cell replacement therapy for neurodegenerative diseases, including glaucoma.


Purification of proteinase-like and Na+/K(+)-ATPase stimulating substance from plasma of insulin-dependent diabetics and its identification as alpha 1-antitrypsin.
The purpose of this study was to purify and identify the proteinase-like substance previously recognized as responsible for the Na+/K(+)-ATPase stimulating property of plasma from insulin-dependent diabetic subjects. Anion-exchange chromatography followed by two-step heparin affinity chromatography resulted in a fraction highly enriched in both potent Na+/K(+)-ATPase stimulating activity and potent proteolytic activity. Approx. 400 micrograms of purified protein was isolated from 62 mg of starting plasma proteins. When analyzed on sodium dodecyl sulfate gels the active fraction consisted mainly of one polypeptide band with an apparent molecular mass of 66 kDa under either reducing or nonreducing conditions. The proteinase-like properties of the purified fraction were further revealed by its ability to clot plasma, split fibrinogen with production of fibrinopeptide A and induce shape change in human platelets and irreversible platelet aggregation in the presence of the stable analogue of endoperoxides U46619. Its additional capacity to affect platelet phosphoinositol metabolism was shown by the stimulation of protein kinase C-dependent phosphorylation of 47 kDa platelet membrane protein. In designing an identification protocol for the purified fraction, it was postulated that plasma proteinases are probably bound to their inhibitors, to form a stable covalently linked complex. The possibility that a proteinase-proteinase inhibitor complex was purified instead of single proteinase(s) was investigated. Neither trypsin nor neutrophil elastase were present in the active fraction whereas, among the possible plasma proteinase inhibitors tested, immunoreactivity was observed only in the presence of alpha 1-antitrypsin (alpha 1 AT) antiserum. Double immunodiffusion showed that control human alpha 1 AT and the plasma-purified fraction shared common antigens. Furthermore, both isoelectric focusing and amino acid composition analysis showed that the two substances were similar. The results obtained indicate that alpha 1 AT is apparently the only active component of the purified fraction from the plasma of insulin-dependent diabetics, thus suggesting that an altered form of the inhibitor is responsible for the broad range of proteinase-like effects elicited by the plasma-purified fraction.


Deep learning, reinforcement learning, and world models.
Deep learning (DL) and reinforcement learning (RL) methods seem to be a part of indispensable factors to achieve human-level or super-human AI systems. On the other hand, both DL and RL have strong connections with our brain functions and with neuroscientific findings. In this review, we summarize talks and discussions in the "Deep Learning and Reinforcement Learning" session of the symposium, International Symposium on Artificial Intelligence and Brain Science. In this session, we discussed whether we can achieve comprehensive understanding of human intelligence based on the recent advances of deep learning and reinforcement learning algorithms. Speakers contributed to provide talks about their recent studies that can be key technologies to achieve human-level intelligence.


Prognostic determinants in patients with uterine and ovarian clear carcinoma.
The purpose of this study is to analyze and compare the demographics, treatment, recurrence, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). A retrospective review of the Cancer Registry database was performed. All patients with UCCC and OCCC who underwent surgical staging at the two participating institutions, between January, 1995 and December, 2007, were identified. Categorical variables were evaluated by Chi square test. Survival estimates were plotted utilizing the Kaplan-Meier method. Analysis of 41 women with UCCC and 121 with OCCC was performed. In patients with OCCC, 48.4% had localized disease, 18.9% had regional spread, 31.1% had distant metastasis, and in 1.6% spread is unknown; compared to UCCC, 41.5% had localized disease, 12.2% regional spread, and 46.3% distant metastasis (p=0.2). The median progression free survival was 31.4 months in women with UCCC, compared to 145 months in patients with OCCC (p=0.04). UCCC women had a median overall survival of 39.5 months, compared to 155.8 months in patients with OCCC (p=0.002). In the multivariate Cox regression model, age>55 years old, tumor extension, optimal cytoreduction, and platinum-based chemotherapy were identified as independent predictors of overall survival. UCCC vs. OCCC was not associated with decreased overall survival in multivariate analysis. OCCC and UCCC have the same rate of localized disease, regional spread and distant metastasis. After controlling for age, tumor extension, optimal cytoreduction, and platinum based chemotherapy, UCCC was not associated with decreased overall survival compared to OCCC.


Slug numbers, biomass and respiratory metabolism in a beech woodland - Wytham Woods, Oxford.
Four species of slug occurred on the site but a single species, Arion hortensis Férussac, dominated in terms of numbers, biomass and respiratory metabolism. This species was found to have two main generations per year, a finding which contrasts with the annual life-cycle described for arable situations in NE England. A majority of slugs was found in areas with deep leaf litter and ground vegetation. Mean annual population density was 34 m-2 while mean biomass equalled 266 mg d.wt.m-2. Respiratory metabolism was calculated to be in a range equivalent to 18.101-29.686 kJ m-2 yr-1. The most probable figure for annual food consumption was estimated at 3 to 4 g d.wt. m-2 yr-1 i.e. 1.28 to 1.70% of ground litter disappearance yr-1. The P/B ratio was 3.1 and net population production efficiency 36.4%.


Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals.
We have investigated the evolution of the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants at 8 months after Pfizer-BNT162b2 vaccination in coronavirus disease 2019 (COVID-19)-naive (n = 21) and COVID-19-convalescent (n = 21) individuals. Neutralizing levels declined for all variants (range 2- to 3.7-fold). Eight months after vaccination, a significant proportion (4/21) of naive individuals lacked detectable neutralizing activity against the highly transmissible SARS-CoV-2 delta variant. In the convalescent group, the impressive high initial humoral response resulted in detectable neutralizing antibody levels against all variants throughout this period.


Functional restoration for recurrent laryngeal paralysis: an experimental study.
The purpose of this investigation was to exclude abductor disturbance and to maintain phonation during recurrent laryngeal nerve paralysis through a new surgical design. This new method consists of implantation of the ansa hypoglossi and sternothyroid muscle pedicle which has been shown to provide sufficient abductor function in a recent publication, and the selective severance of the abductor branch after neurorrhaphy of the recurrent laryngeal which is shown to be a sufficient adductor function in another study. The recovery of sufficient abductor function during inspiration and dyspnea was 67% and 89% of adductor function with phonation. However, after cutting an adductor nerve branch of the recurrent laryngeal nerve in cases of insufficient abduction, the vocal cord on the operated-on side regained abduction during inspiration. The effect of the ansa hypoglossi and sternothyroid muscle pedicle is also discussed.


The mechanistic landscape of Lytic transglycosylase as targets for antibacterial therapy.
Lytic transglycosylases (Ltgs) are glycan strand cleaving enzymes whose role is poorly understood in the genesis of the bacterial envelope. They play multiple roles in all stages of a bacterial life cycle, by creating holes in the peptidoglycan that is necessary for cell division and separation. Here, we review recent advances in understanding the suitability of Ltgs as antibacterial drug targets. We specifically highlight a known inhibitor bulgecin A that is able to inhibit the function of structurally diverse Ltgs, as well as synergize with beta-lactams to improve its efficacy in antibiotic insensitive strains. Discovery of new antibiotics or new targets has been challenging. These studies could provide a viable path toward designing broad-spectrum inhibitors that targets Ltgs.


Utilization of health care services by elderly for respiratory diseases including TB - Challenges.
Progressive functional decline of all body organ systems in association with decreased immunity makes elderly vulnerable to all types of diseases including respiratory diseases. Advances in medical fields have resulted in increasing proportion of elderly globally. Healthcare demands of elderly population are complex. Provision of healthcare services for this continuously increasing population subgroup & ensuring their adequate utilization is full of challenges. These are demographic, socioeconomic, financial, physical accessibility, quality of healthcare services, attitudinal & transportation related. Large size of this subgroup with special healthcare needs in context of limited available resources of middle income country like India is the biggest challenge. Poor educational status & socioeconomic condition of Indian elderly, dependence on family, absence of formal social security & healthcare security complicates situation further. Condition of elderly females is particularly worse. In view of poor physical ability with often associated physical disability makes accessibility of healthcare services also significant factor. Overcoming negative attitudinal factors prevalent in Indian elderly & make them utilize available healthcare services is another huge challenge. Quality of healthcare services in form of availability of required expertise & equipments, attitude of healthcare providers towards elderly patients & convenience in utilization of these services also play an important role. Special provisions in TB control program for elderly in view of their complex needs, high prevalence, morbidity & mortality are also required.


Respiratory effects of inhalation exposure among workers during the clean-up effort at the World Trade Center disaster site.
During December 2001 we conducted a field study of 183 clean-up and recovery workers at the World Trade Center (WTC) disaster site to assess respiratory health effects potentially resulting from their work at the site. On site, we administered a respiratory health questionnaire designed to assess upper respiratory symptoms and lower respiratory symptoms, including cough, phlegm, and wheeze, as well as indices of exposure, including number of days worked at the site and job category. Spirometry was conducted for 175 workers. Sixty-five percent of the workers surveyed arrived at the site without lower respiratory symptoms. Of this group, 34% developed cough, 24% developed phlegm, and 19% developed wheeze. Prevalence rates of these symptoms were related to the number of days spent working at the WTC, but not job category. The mean percentage predicted FEV(1) and FVC were 6% and 5% lower, respectively, for workers who developed new lower respiratory symptoms compared to those who remained symptom free. While the development of new wheeze suggested the presence of airway obstruction, the near-normal distribution of age-adjusted FEV(1)/FVC ratios suggested that the degree of obstruction was mild. The prevalence rates of upper airway symptoms (nasal congestion, sore throat, hoarse throat) exceeded those of lower respiratory symptoms, however, it was not determined whether symptoms pre-dated arrival at the WTC site.


Occurrence of Irgarol 1051 and its major metabolite in Maryland waters of Chesapeake Bay.
Irgarol and its major metabolite (GS26575) were measured in Maryland waters of Chesapeake Bay: (1) in and near 10 marinas, a mainstem Bay site and two Severn River locations during a general survey in July and December of 2002; (2) at various sites in the Port Annapolis Marina and the Severn River area during March of 2002 before the boating season began; and (3) during July (peak boating season) in the same Port Annapolis Marina and Severn River sites area during both an ebb and flood tide. Irgarol concentrations ranged from 1.82 ng/l at the mid-Bay site to 585 ng/l in Port Annapolis marina during the July and December general survey. An Irgarol 90th centile of 239 ng/l was reported for the 10 marina sites, two Severn River sites and one mainstem site sampled during the general survey conducted in July and December. Temporal analysis of all pooled data showed that 90th centiles were over seven times higher in July when compared to December. A comparison of Irgarol concentrations at 12 sites in the Port Annapolis marina and Severn River area during both an ebb and flood tide in July showed no consistent trend with tidal cycle by site although significant reductions in concentrations were reported with distance from the three Port Annapolis marina sites. Ecological risk from Irgarol exposure was judged to be low for most Chesapeake Bay sites sampled. Possible exceptions were Port Annapolis marina, Severn River sites in close proximity to this marina and Chesapeake Harbor marina where Irgarol concentrations exceeded a conservative effects threshold during the peak boating season in July. Ecological risk from GS26575 exposure was low for all sites.


Activation of mitochondrial oxidative metabolism by calcium ions in Limulus ventral photoreceptor.
Cells regulate their metabolic energy production to meet the requirements of their energy consuming activities. For most animal cells the prime site of energy production, in the form of ATP, is the mitochondrion. Extensive in vitro studies of isolated mitochondria have provided detailed information about the specific biochemical reactions involved in energy production. At present there is a debate about whether respiration in excitable cells is controlled by the availability of ADP to the mitochondrion and/or by calcium ions. Using the large ventral photoreceptor of the horseshoe crab (Limulus polyphemus) we describe a method for measuring the transient increase in the mitochondrial O2 consumption (delta QO2) following a flash of light of a single photoreceptor. We then show that this delta QO2 results in part from a rise in the intracellular concentration of calcium (Cai).


Thymoma. A clinicopathologic review.
The clinical and pathologic features of 283 patients with thymoma treated at the Mayo Clinic (147 female and 136 male; ages 16 years to 90 years; mean, 52 years) were examined. Forty-six percent of the patients had myasthenia gravis and 10% had other paraneoplastic phenomena. The tumors were locally invasive at operation in 32%, including 6% with metastasis to lung or pleura. Intrathoracic recurrence was noted postoperatively in 15% of those who had total excision and distant metastasis developed in 3% of patients. Thirteen percent died of their thymomas and 16% died of myasthenia. Overall 5-year survival was 67% and 10-year survival was 53%. Poor prognostic factors included presence of tumor-related symptoms, large tumor size, local invasion or metastasis in initial operation, and predominantly epithelial histologic features. Although true thymomas are composed of cytologically benign elements, they show a propensity for local invasion and intrathoracic recurrence. They rarely metastasize outside the thorax.


On the action of diethyldithiocarbamate as inhibitor of copper-zinc superoxide dismutase.
The rate constants of the reactions between pulse radiolytically produced superoxide radicals and the Cu(II) chelate of diethyldithiocarbamate were determined at pH 7.0. It was found that diethyldithiocarbamate forms a copper complex, which as no dismutating activity. The removal of the protein bound copper in superoxide dismutase by diethyldithiocarbamate yields the same effect as coordination of the copper in the enzyme.


Return to Play After Anterior Cruciate Ligament Reconstruction with Extra-Articular Augmentation: A Systematic Review.
The purpose of the current study is to systematically review the current evidence in the literature to ascertain rates of return to play after ACLR with extra-articular augmentation (EA). A literature search was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they evaluated and reported on return to play after ACLR + EA; case studies and review articles were excluded. The outcomes measured focused on (1) return to play, (2) return to play at the same or higher level, and (3) timing of return to play. Qualitative analysis and quantitative analysis were performed using SPSS. Overall, 19 studies met our inclusion criteria. Among patients undergoing primary ACLR, 82.8% to 100% were able to return to play, with 64% to 100% able to return at the same or higher level of play. All professional athletes were able to return to play, and 85.7% to 100% were able to return to the same level of preoperative play. The mean time to return was 5 to 11 months in those undergoing primary ACLR + EA. Among those undergoing revision ACLR, 50% to 88.4% were able to return to play, with 41.5% to 77.8% able to return at the same or higher level of play. None of the 5 studies that compared rate of return to play (at any level) between ACLR + EA and ACLR alone found a significant difference between them. However, among the 6 studies that compared rate of return to play at the same level between ACLR + EA and ACLR alone, 2 studies found a significantly higher rate of return to play with ACLR + EA. ACLR + EA resulted in high levels of return to play in those undergoing either primary or revision ACLR. Additionally, comparative studies of patients undergoing primary ACLR with or without EA reported similarly high rates of return to play. Level IV, systematic review of level I to IV studies.


Experience with intravesical bacillus Calmette-Guèrin therapy of superficial bladder tumors.
Between March, 1978, and July, 1981, 86 patients with polychronotopic superficial papillary bladder tumors and concurrent carcinoma in situ were randomized to receive either transurethral resection alone (43) or TUR plus BCG (43). The results indicate that BCG is not only active in preventing recurrences of new tumors but also effective for the diffuse, flat carcinoma in situ.


Identification of risk factors for hypertension and tachycardia upon dexmedetomidine discontinuation.
Dexmedetomidine may cause hypertension and tachycardia upon discontinuation. Risk factors are poorly described but may include prolonged infusion, higher doses, a history of hypertension, and abrupt cessation. This study aims to identify risk factors for hypertension and tachycardia upon dexmedetomidine discontinuation. In this single-center, case-control study, critically ill patients requiring dexmedetomidine for 6 h or more were screened for hypertension or tachycardia within 24 h of discontinuation. We compared baseline and dexmedetomidine-specific data between patients who developed hypertension or tachycardia (cases) and those who did not (controls) and used logistic regression to identify independent risk factors. Of 110 patients, 35 (31.8%) experienced hypertension or tachycardia. When comparing cases to controls, the maximum dexmedetomidine dose was 0.7 and 0.75 μg/kg/h (p = .54), cumulative dose was 1174.5 and 1063.5 μg/kg/h (p = .43), and duration was 31and 23.25 h (p = .22), respectively. Only a past medical history of hypertension was an independent predictor of hypertension or tachycardia upon dexmedetomidine discontinuation. Approximately one third of patients experienced hypertension or tachycardia upon dexmedetomidine discontinuation. A past medical history of hypertension was the only independent risk factor identified in this study based on the clinical data collected.


Archaeal and Bacterial Diversity and Distribution Patterns in Mediterranean-Climate Vernal Pools of Mexico and the Western USA.
Biogeographic patterns in microorganisms are poorly understood, despite the importance of microbial communities for a range of ecosystem processes. Our knowledge of microbial ecology and biogeography is particularly deficient in rare and threatened ecosystems. We tested for three ecological patterns in microbial community composition within ephemeral wetlands-vernal pools-located across Baja California (Mexico) and California (USA): (1) habitat filtering; (2) a latitudinal diversity gradient; and (3) distance decay in community composition. Paired water and soil samples were collected along a latitudinal transect of vernal pools, and bacterial and archaeal communities were characterized using 16S rDNA sequencing. We identified two main microbial communities, with one community present in the soil matrix that included archaeal and bacterial soil taxa, and another community present in the overlying water that was dominated by common freshwater bacterial taxa. Aquatic microbial communities were more diverse in the north, and displayed a significant but inverted latitudinal diversity pattern. Aquatic communities also exhibited a significant distance-decay pattern, with geographic proximity, and precipitation explaining part of the community variation. Collectively these results indicate greater sensitivity to spatial and environmental variation in vernal pool aquatic microbial communities than in soil microbial communities. We conclude that vernal pool aquatic microbial communities can display distribution patterns similar to those exhibited by larger organisms, but differ in some key aspects, such as the latitudinal gradient in diversity.


The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
The zinc finger X-linked duplicated (ZXD) family of transcription factors has been implicated in regulating transcription of major histocompatibility complex class II genes in antigen presenting cells; roles beyond this function are not yet known. The expression of one gene in this family, ZXD family zinc finger C (ZXDC), is enriched in myeloid lineages and therefore we hypothesized that ZXDC may regulate myeloid-specific gene expression. Here we demonstrate that ZXDC regulates genes involved in myeloid cell differentiation and inflammation. Overexpression of the larger isoform of ZXDC, ZXDC1, activates expression of monocyte-specific markers of differentiation and synergizes with phorbol 12-myristate 13-acetate (which causes differentiation) in the human leukemic monoblast cell line U937. To identify additional gene targets of ZXDC1, we performed gene expression profiling which revealed multiple inflammatory gene clusters regulated by ZXDC1. Using a combination of approaches we show that ZXDC1 activates transcription of a gene within one of the regulated clusters, chemokine (C-C motif) ligand 2 (CCL2; monocyte chemoattractant protein 1; MCP1) via a previously defined distal regulatory element. Further, ZXDC1-dependent up-regulation of the gene involves eviction of the transcriptional repressor B-cell CLL/lymphoma 6 (BCL6), a factor known to be important in resolving inflammatory responses, from this region of the promoter. Collectively, our data show that ZXDC1 is a regulator in the process of myeloid function and that ZXDC1 is responsible for Ccl2 gene de-repression by BCL6.


[Stone therapy-use and limitations of the guidelines].
Increase of medical knowledge, technical innovation together with a demographic change, and increase of stone incidence in daily practice challenges guideline preparation and clinical studies. Increasing interdisciplinary collaboration in stone treatment can also be demonstrated in the number of affiliated professional and working groups in the current guideline update. The following case illustrates treatment options in a symptomatic patient harbouring bilateral stones and metabolic risk factors. Decision guidance for treatment and recurrence prevention measures are presented on the basis of expert opinion and available published evidence.


Molecular concordance of concurrent Candida albicans candidemia and candiduria.
The significance of candiduria remains unclear. We correlated Candida albicans candidemia with candiduria by molecular genotyping. 33 pairs of concurrent blood and urine C. albicans isolates from 31 adult (≥ 18 years) were genotyped with infrequent-restriction-site PCR. The molecular concordance rates of three major genotypes were 100% for I, 82% for II, and 71% for III. The molecular concordance between concurrent C. albicans candidemia and candiduria was frequent. Our findings substantiate the importance of candiduria in appropriate clinical context as the majority of our patients were from intensive care units.


The analysis and assay of cyclic nucleotide phosphodiesterase isoenzyme activity.
Greater knowledge over the past decade on the biochemical properties, as well as the identification of specific pharmacological tools has led to a marked improvement in the methods employed for the analysis and assay of PDE isoenzymes. A major message has been the marked species and tissue-dependent variation in the distribution of the various isoenzymes and their subtypes. This has great implications not only in terms of extrapolating animal data to the human situation, but also from one tissue to another. Thus, it is critical, in particular for drug discovery efforts, to characterize human PDEs in the relevant tissue. Molecular cloning is probably the best and most direct route to achieve this objective since access to disease-free human tissue is heavily limited. Alternatively, well-characterized animal tissues showing PDE and pharmacological profiles similar to human tissues may be utilized. The methods described in this chapter have been successfully applied to study to the biochemistry and pharmacology of PDEs in both animal and human tissues, and in the discovery of novel selective inhibitors for these proteins.


Adenocarcinoma of the duodenum arising from Brunner's gland resected by partial duodenectomy: a case report.
Duodenal carcinoma originating in Brunner's gland is rare. Herein, we report a case of duodenal carcinoma arising from Brunner's gland in a 63-year-old man. On diagnostic imaging, the lesion presented as a non-invasive carcinoma; the patient also had uncontrolled diabetes and liver cirrhosis. Hence, we decided to perform partial duodenectomy to reduce operative stress. Pathological examination revealed that the tumor consisted of tissue from Brunner's gland. Additionally, the carcinoma cells were strongly positive for Mucin-6 protein, which is an epithelial marker of Brunner's gland. The patient's post-operative course was uneventful, and he has been well for 2 years after the surgery. This a rare case of an adenocarcinoma arising from Brunner's gland of the duodenum that was resected by duodenectomy.


Rhinovirus 39 infection in allergic and nonallergic subjects.
To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.


The effects of cholinergic and dopaminergic antagonists on nicotine-induced cerebral neurotransmitter changes.
In a continuing study of nicotine-induced mechanisms in brain areas associated with cognitive processes, the effects of cholinergic and dopaminergic antagonists on nicotine-induced changes in dopamine, norepinephrine, and serotonin were examined. These effects were measured via in vivo microdialysis in the dorsal and ventral hippocampus and in the prefrontal and medial temporal cortex of conscious, freely moving, adult male rats. Nicotine (0.3 mg/kg, free base) was administered subcutaneously and the antagonists were infused locally via the microdialysis probe. Nicotine alone induced an increase of dopamine and its metabolites in all areas, an increase of norepinephrine in the cortex, and an increase of the norepinephrine metabolite 4-hydroxy-3-methoxy-phenylglycol in all areas. Serotonin was decreased in the hippocampus and increased in the cortex. Nicotine-induced dopamine increases were inhibited by nicotinic (mecamylamine 100 microM, methyllycaconitine 500 microM), muscarinic (atropine 100 microM), and dopaminergic D1 (SCH23390 100 microM) and D2 (eticlopride 100 microM) antagonists, in the hippocampal and cortical areas. In the hippocampal areas, these antagonists had less significant effect on norepinephrine and serotonin. However, in the cortical areas, all antagonists inhibited the nicotine-induced increase of serotonin to varying degrees; and some, primarily nicotinic and dopamine D1 antagonists, inhibited the induced increase of norepinephrine. In the hippocampal and cortical areas, the mechanisms of nicotine-induced dopamine increase seem to be similar, but the mechanisms seem to be different for noradrenergic and serotonergic systems, as shown by the fact that nicotine induces no change in norepinephrine and a decrease in serotonin in the hippocampus, while it induces an increase in both in the cortex. Nicotine-induced dopamine release seems to be mediated, in part locally, by nicotinic and muscarinic receptors on dopaminergic cells. In contrast, nicotine's effect on norepinephrine and serotonin is at least partially mediated by initial changes at other than local sites, and through different receptors. Thus, the effects of nicotine and the mechanisms involved differ for different neurotransmitters and in different brain areas.


Cardiac Rehabilitation Programs for Cancer Survivors: A Scoping Review.
Participation in cardiac rehabilitation is associated with improved quality of life and physical functioning and may be an effective strategy to assist in the recovery from cancer. We conducted a scoping review to identify studies that enrolled cancer survivors into cardiac rehabilitation programs. We identified nine studies that included 662 cancer survivors. Five studies integrated cancer survivors and cardiac patients into the same sessions, three studies developed cancer-only rehabilitation sessions, and one study did not report details on the rehabilitation sessions. On average, more than 60% of enrolled cancer survivors completed the rehabilitation programs and many health and psychosocial outcomes improved after rehabilitation. Cardiac rehabilitation appears to be acceptable and favorably impacts many health and psychosocial outcomes among cancer survivors. Future research should consider randomized controlled trial study designs, enrolling diverse survivor populations, and using a set of core physical function and psychosocial outcomes.


Recommending COVID-19 vaccination for adolescents in primary care.
COVID-19 vaccines are available for adolescents in the United States, but many parents are hesitant to have their children vaccinated. The advice of primary care professionals strongly influences vaccine uptake. We examined the willingness of primary care professionals (PCPs) to recommend COVID-19 vaccination for adolescents. Participants were a national sample of 1,047 US adolescent primary care professionals. They participated in an online survey in early 2021, after a COVID-19 vaccine had been approved for adults but before approval for adolescents. Respondents included physicians (71%), advanced practice providers (17%), and nurses (12%). We identified correlates of willingness to recommend COVID-19 vaccination for adolescents using logistic regression. The majority (89%) of respondents were willing to recommend COVID-19 vaccination for adolescents, with advanced practice providers and nurses being less likely than paediatricians to recommend vaccination (84% vs. 94%, aOR 0.47, 95% CI 0.23-0.92). Respondents who had received at least one dose of a COVID-19 vaccine were more likely to recommend adolescent vaccination (92% vs. 69%, aOR 4.20, 95% CI 2.56-6.87) as were those with more years in practice (94% vs. 88%, aOR 2.93, 95% CI 1.79-4.99). Most respondents (96%) said they would need some measure of support in order to provide COVID-19 vaccination to adolescents, with vaccine safety and efficacy information being the most commonly cited need (80%). Adolescent primary care professionals were generally willing to recommend COVID-19 vaccination. However, most indicated a need for additional resources to be able to administer COVID-19 vaccines at their clinic.


A possible route towards dissipation-protected qubits using a multidimensional dark space and its symmetries.
Quantum systems are always subject to interactions with an environment, typically resulting in decoherence and distortion of quantum correlations. It has been recently shown that a controlled interaction with the environment may actually help to create a state, dubbed as "dark", which is immune to decoherence. To encode quantum information in the dark states, they need to span a space with a dimensionality larger than one, so different orthogonal states act as a computational basis. Here, we devise a symmetry-based conceptual framework to engineer such degenerate dark spaces (DDS), protected from decoherence by the environment. We illustrate this construction with a model protocol, inspired by the fractional quantum Hall effect, where the DDS basis is isomorphic to a set of degenerate Laughlin states. The long-time steady state of our driven-dissipative model exhibits thus all the characteristics of degenerate vacua of a unitary topological system.


Parental focus of attention in a videotape feedback task as a function of hypothesized risk for offspring schizophrenia.
The families of 29 disturbed but nonpsychotic adolescents were observed in a structured task in which they discussed their reactions to viewing themselves interacting on videotape. Measures derived from the Singer-Wynne concenpt of transactional style deviance were applied to the parental behaviors and related to prior assessments of parental communication disorder based on individual parental TAT protocols. The results confirm the Singer-Wynne hypothesis of the cross-situational stability of transactional style deviance. The most striking finding, however, is that an index of positive focusing behavior differentiates more strongly parents of adolescents hypothesized to be at varying leves of risk for schizophrenia than does the measure of transactional style deviance.


[Long-term medical complications of Holocaust trauma].
Holocaust survivors are currently confronted with the problems inherent to ageing such as illness, frailty, dependency and isolation. A study was carried out to assess the long-term medical consequences of the Holocaust trauma.


The product of rab2, a small GTP binding protein, increases neuronal adhesion, and neurite growth in vitro.
The rab genes code for small GTP binding proteins that share with p21ras the ability to bind and hydrolyze GTP. They present significant sequence homologies with the products of YPT1 and SEC4, two small GTP binding proteins involved in the regulation of secretion in the yeast. Several rab genes are expressed in the developing and adult mouse brain. To test directly the possible involvement of these genes in neuronal differentiation, purified rab proteins produced in E. coli were introduced into neurons dissociated from E15 rat midbrain. The most striking effects were obtained with rab2 protein (rab2p). Compared with untreated cells, neurons loaded with rab2p presented an enhanced adhesion to the culture substratum. This phenomenon was visible 3 hr after seeding and was followed within 24 hr by a dramatic increase in neurite growth. Loading the same population of neurons with the products of four other rab genes either decreased neuronal adhesion and neurite growth or had no effect. These experiments suggest that the expression of rab2p plays an important role in neuronal differentiation.


Early changes in photopic negative response in eyes with glaucoma with and without choroidal detachment after filtration surgery.
To evaluate the electroretinographic (ERG) changes in the early postoperative period following glaucoma filtration surgery, and its relationship with choroidal detachment (CD). This retrospective observational single-centre study included 57 consecutive patients with primary open-angle glaucoma who underwent unilateral glaucoma filtration surgery. The patients were divided into two groups according to the presence or absence of CD. ERG components, including the photopic negative response (PhNR), a-wave and b-wave were compared before and after surgery using skin electrodes. There were 46 patients in the non-CD group and 11 in the CD group. ERG was recorded within 5.1 (2.1 to 8.1) (mean (95% CI)) days after surgery. In the non-CD group, the PhNR amplitude, PhNR/b-wave amplitude ratio and PhNR implicit time improved significantly after surgery (p=0.008, 0.002 and 0.039, respectively). In the CD group, the amplitude of the PhNR, a-wave and b-wave were significantly deteriorated after surgery (p=0.002, 0.001 and 0.001, respectively). Postoperative intraocular pressure (IOP) (p=0.031) and postoperative CD (p<0.001) were significantly associated with change in the PhNR amplitude in the univariate models. In the multivariate analysis, severe CD (stage 3) cases tended to be deteriorated more. Even in the early postoperative period within several days, the PhNR amplitude increased with IOP lowering following filtration surgery in the absence of CD. The presence of CD may arrest the improvement of the retinal ganglion cell function. The present results enhance understanding the structural and functional recovery after glaucoma surgery and the role of postoperative CD.


Partitioning of bile acids into subcellular organelles and the in vivo distribution of bile acids in rat liver.
1. The subcellular distribution of conjugates of cholic acid and chenodeoxycholic acid between cytosol, nuclei, mitochondria and microsomes in rat liver has been determined. 2. The partition coefficients for the distribution of these bile acids between subcellular fractions and buffer have been measured and used to construct a compartmental model of the amounts of conjugated bile acids present in the different subcellular organelles in vivo. 3. This model indicates that a large percentage of the bile acid in the rat liver is found in the nuclear fraction; 42% of the cholic acid conjugates and 27% of the chenodeoxycholic acid conjugates. Substantial amounts of bile acid are also present in microsomes and mitochondria suggesting that published estimates of the amounts of bile acids in these fractions are underestimates. 4. The model also allows the amount of bile acid which is in free solution in cytosol to be determined; 10.9% of the cholic acid conjugates and 4.1% of the chenodeoxycholic acid conjugates in rat liver were present in this fraction. Knowlege of the amount of free bile acid allows possible roles of the cytosolic bile binding proteins to be assessed.


A combination of the aldose reductase inhibitor, statil, and the prostaglandin E1 analogue, OP1206.alpha CD, completely improves sciatic motor nerve conduction velocity in streptozocin-induced chronically diabetic rats.
In view of the possible implication of multifactorial mechanisms in the pathogenesis of diabetic neuropathy, the aldose reductase inhibitor (ARI), Statil, which ameliorates abnormal sorbitol or myo-inositol metabolism in diabetic nerves, and the prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), which improves diabetic vascular derangements, were administered simultaneously for 2 months to streptozocin (STZ)-induced diabetic rats with 5 months' duration of diabetes, and the effects on sciatic motor nerve conduction velocity (MNCV), Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, and morphology of myelinated nerve fibers (MNF) were compared with the effects of a monotherapy with OP. The combination regimen ameliorated abnormal nerve sorbitol and myo-inositol levels and normalized decreased MNCV and enzyme activity. In contrast, neither sorbitol nor myo-inositol metabolism was ameliorated, and only insufficient improvement of MNCV and morphology of MNF was obtained with a monotherapy with OP. In addition, the combination therapy reversed both a decrease in the percent of large MNF and an increase in the percent of small MNF in diabetic rats, whereas a monotherapy with OP reversed only a decrease in the percent of large MNF. The results might suggest that a multiple-drug therapy with different mechanisms of action has greater effects on diabetic neuropathy than a single-drug therapy and is worthy of clinical consideration.


Cimetidine-procainamide pharmacokinetic interaction in man: evidence of competition for tubular secretion of basic drugs.
The hypothesis that basic drugs can compete for active tubular secretion by the kidney was tested in six healthy volunteers by comparing the single dose pharmacokinetics of oral procainamide before and during a daily dose of cimetidine. The area under the procainamide plasma concentration-time curve was increased by cimetidine by an average of 35% from 27.0 +/- 0.3 micrograms/ml X h to 36.5 +/- 3.4 micrograms/ml X h. The elimination half-life increased from an harmonic mean of 2.92 to 3.68 h. The renal clearance of procainamide was reduced by cimetidine from 347 +/- 46 ml/min to 196 +/- 11 ml/min. All these results were statistically significant (p less than 0.016). The area under the plasma concentration-time curve for n-acetylprocainamide was increased by a mean of 25% by cimetidine due to a significant (p less than 0.016) reduction in renal clearance from 258 +/- 60 ml/min to 197 +/- 59 ml/min. The data suggests that cimetidine inhibits the tubular secretion of both procainamide and n-acetylprocainamide, and, if so, represents the first documented evidence for this type of drug interaction in man. The clinical implications from this study necessitate dosage adjustments of procainamide in patients being concomitantly treated with cimetidine. The interaction is pertinent not only for basic drugs that are cleared by the kidney, but also for metabolites of basic drugs and endogenous substances which require active transport into the lumen of the proximal tubule of the kidney for their elimination.


Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate.
Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.


Robust, Generalizable, and Interpretable Artificial Intelligence-Derived Brain Fingerprints of Autism and Social Communication Symptom Severity.
Autism spectrum disorder (ASD) is among the most pervasive neurodevelopmental disorders, yet the neurobiology of ASD is still poorly understood because inconsistent findings from underpowered individual studies preclude the identification of robust and interpretable neurobiological markers and predictors of clinical symptoms. We leverage multiple brain imaging cohorts and exciting recent advances in explainable artificial intelligence to develop a novel spatiotemporal deep neural network (stDNN) model, which identifies robust and interpretable dynamic brain markers that distinguish ASD from neurotypical control subjects and predict clinical symptom severity. stDNN achieved consistently high classification accuracies in cross-validation analysis of data from the multisite ABIDE (Autism Brain Imaging Data Exchange) cohort (n = 834). Crucially, stDNN also accurately classified data from independent Stanford (n = 202) and GENDAAR (Gender Exploration of Neurogenetics and Development to Advanced Autism Research) (n = 90) cohorts without additional training. stDNN could not distinguish attention-deficit/hyperactivity disorder from neurotypical control subjects, highlighting the model's specificity. Explainable artificial intelligence revealed that brain features associated with the posterior cingulate cortex and precuneus, dorsolateral and ventrolateral prefrontal cortex, and superior temporal sulcus, which anchor the default mode network, cognitive control, and human voice processing systems, respectively, most clearly distinguished ASD from neurotypical control subjects in the three cohorts. Furthermore, features associated with the posterior cingulate cortex and precuneus nodes of the default mode network emerged as robust predictors of the severity of core social and communication deficits but not restricted/repetitive behaviors in ASD. Our findings, replicated across independent cohorts, reveal robust individualized functional brain fingerprints of ASD psychopathology, which could lead to more objective and precise phenotypic characterization and targeted treatments.


Postprandial lipaemia and haemostatic factors.
Factor VII activity (FVIIc), a reported risk factor for fatal coronary heart disease, increases transiently after a fat-rich meal. The response shows dose-response characteristics and peak FVIIc and triglyceride concentrations above fasting levels tend to be positively associated. The mechanism is incompletely understood, but appears to require factor IX and the presence in plasma of lipoprotein products of lipolytic activity. Factor XII is not apparently essential. The increase in FVIIc is due to raised activated factor VII (FVIIa) activity, but is not associated with increased thrombin production or changes in fibrinolytic activity. The response of FVIIa appears independent of the proportions of saturated, monounsaturated and polyunsaturated fatty acids in the dietary fat, although dietary stearic acid may be less effective than myristic acid. However, in one study in which deliberate efforts were made to force an increase in plasma free stearic acid, its plasma level was positively associated with postprandial FVIIc. Because FVIIa initiates the thrombotic response to rupture of an atheromatous plaque, a raised postprandial level may represent a transient rise in the likelihood of a clinically significant coronary thrombosis.


Smartphone-assisted paper-based multifunctional assay for on-site tandem detection of inorganic phosphate, neutral red and heparin.
Today, easy availability and efficient detection assays in low-resource settings are mandatory. Therefore, a smartphone-assisted paper-based detection strategy using eosin Y (EY)-embed ZIF-8 nanocomposite for phosphate (Pi), neutral red (NR) and heparin (HP) on site testing was fabricated. After adding the targets in a specific order, the prepared strips produced brilliant color transitions (astonishing colors, ranging from pistachio to bright yellow for Pi, from bright yellow to jacinth for NR and from jacinth to light orange for HP). These variation on tonality can be evaluated by the smartphone-based readout device (Color Assist App) through the ratio change of B/(R + G + B), which exhibits superior performance of on-site detection in wastewater, including high sensitivity (LOD is 0.015, 0.031 and 0.014 mM for Pi, NR and HP, respectively), ultra-fast response time and excellent selectivity. This strips and smartphone dual-mode monitoring strategy may offer a convenient idea to identify Pi, NR and HP, with great prospects for environmental wastewater applications. Additionally, the probe was enabled for bioimaging of Pi, NR and HP in living cells. Finally, the related anti-counterfeiting fluorescent ink of probe was proposed on schedule.


Antral or Pyloric Deformity Is a Risk Factor for the Development of Postendoscopic Submucosal Dissection Pyloric Strictures.
Surgeons must be aware of risk factors for strictures before performing endoscopic submucosal dissection (ESD), to enable early interventions to prevent severe strictures. This study was a single-center retrospective study. We reviewed the clinical data of patients who has undergone gastric ESD from January 2007 to December 2012. Among the 3,819 patients who had undergone gastric ESD, 11 patients (7.2%) developed pyloric strictures and received successful endoscopic balloon dilation. Significant differences were noted between the patients without and with post-ESD strictures for pretreatment of antral or pyloric deformities (46.4% vs 81.8%), the proportion of extension to the lumen circumference (>3/4, 9.4% vs 54.5%), the longitudinal extent of mucosal defects (27.9±10.1 mm vs 51.5±10.8 mm), and post-ESD bleeding (2.9% vs 27.3%). Multivariate analysis revealed that pretreatment antral or pyloric deformities (odds ratio [OR], 30.53; 95% confidence interval [CI], 1.476 to 631.565; p=0.027), larger longitudinal extent of mucosal defects (OR, 1.20; 95% CI, 1.074 to 1.340; p=0.001), and circumferential extension of ≥3/4 (OR, 13.69; 95% CI, 1.583 to 118.387; p=0.017) were independent risk factors for post-ESD stricture. Antral or pyloric deformities, sub-circumferential resection over more than 75% of the circumference and greater longitudinal extent of mucosal defects are independent risk factors for post-ESD stricture.


Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age.
To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present. Transcatheter PDA closure; conventional, Doppler, and tissue Doppler imaging; and speckle tracking echocardiography. To determine the feasibility and reliability of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in children undergoing transcatheter PDA closure. Forty-two children diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler, and tissue Doppler imaging, and speckle-derived strain rate echocardiography were performed at preclosure and at 48 hours, 1 month, and 6 months postclosure. Tissue Doppler velocities of the lateral and septal mitral valve annuli were obtained. Global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The median age of the patients was 2 years and body weight was 15 kg, with the mean PDA diameter of 3.11 ± 0.99 mm. M-mode measurements (left ventricular end diastolic diameter, left atrium diameter to aortic annulus ratio, ejection fraction, and shortening fraction) reduced significantly early after PDA closure (p < 0.001). After 1 month, left ventricular end diastolic diameter and left atrium diameter to aortic annulus ratio continued to decrease, while ejection fraction and fractional shortening improved significantly. All tissue Doppler velocities showed a significant decrease at 48 hours with significant prolongation of global myocardial function (p < 0.001) and then were normalized within 1 month postclosure. Similarly, global longitudinal strain significantly decreased at 48 hours postclosure (p < 0.001), which also recovered at 1 month follow-up. Preclosure global longitudinal strain showed a good correlation with the postclosure prolongation of the myocardial performance index. Transcatheter PDA closure causes a significant decrease in left ventricular performance early after PDA closure, which recovers completely within 1 month. Preclosure global longitudinal strain can be a predictor of postclosure myocardial dysfunction.