Prediction of nomegestrol acetate pharmacokinetics in healthy female adolescents and adults by whole-body physiology-based pharmacokinetic modelling and clinical validation.
Nomegestrol acetate (NOMAC), a selective progestogen, and 17β-estradiol (E2), which is identical to endogenous oestrogen, are components of a new monophasic combined oral contraceptive--NOMAC/E2. This study aimed to compare pharmacokinetics (PK) of NOMAC in adolescent and adult women following a single dose of NOMAC/E2. Healthy postmenarcheal adolescent (14-17years) and adult (18-50years) women received a single dose of NOMAC/E2 (2.5mg/1.5mg) in this single-centre, open-label, parallel-group Phase 1 study (EudraCT# 2008-002142-38). Blood samples were obtained for PK analysis, and concentrations of NOMAC, E2 and its metabolite estrone (E1) were determined for up to 129h following dosing to obtain PK data. An independent whole-body physiology-based pharmacokinetic (WB-PBPK) simulation model of NOMAC based on an independent Phase 3 dataset was used to scale NOMAC concentration-time plots to adolescents. Overall, 52 women were screened, of whom 30 (15 adolescents and 15 adults) were enrolled. No statistically significant differences were observed between the adolescent and adult groups for the clinically evaluated NOMAC PK parameters [maximum concentration (Cmax), area under the curve (AUC) and half-life (t1/2)]. The PK of E2 and E1 showed extensive overlap between both age groups. The WB-PBPK model accurately predicted NOMAC AUC and Cmax values in both groups. No differences were observed in the clinically evaluated PK parameters for NOMAC between adolescent and adult women after a single dose of NOMAC/E2. The WB-PBPK model accurately predicted NOMAC PK data (EudraCT# 2008-002142-38). PK studies in adolescents are challenging because of ethical considerations. The whole-body physiology-based model described here complements classic noncompartmental and population PK approaches. The utility of this method is its ability to expand to adolescent postmenarcheal girls by using virtual postmenarcheal adolescent population data and applying physiological scaling.


Dynamic stabilization of the painful thumb: A historical and evidence-informed synthesis.
Expert opinion INTRODUCTION: Thumb carpometacarpal joint (CMC) osteoarthritis is a common condition seen in the hand therapy clinic. Prevalence is generally higher in females, and the percentage rises for post-menopausal females. Patients typically present with pain and functional difficulties. Conservative management is recommended before a surgical consult. Evidence is mounting that a dynamic stability modeled approach has a significant effect on pain and improving function. The purpose of this paper is two-fold: first, to present the history and development of a dynamic stabilization model for treatment of the patient with thumb CMC osteoarthritis (OA), and second, to provide expert clinical commentary and recommendations for the treatment of thumb CMC OA in light of the best available evidence. Expert clinical commentary is based on an extensive review of relevant literature. The current literature and expert opinion supports an evidence-informed multimodal intervention: modalities, pain relief techniques, manual release, joint mobilizations as deemed necessary, neuromuscular re-education through proprioceptive exercises, and education in joint protection principles. A rationale for a dynamic stabilization approach is presented. The unique anatomy of the thumb deserves finely tuned care based on high quality research. To advance our knowledge and clinical skills we must not become stagnant, but continue to generate high level evidence. The standard for future thumb CMC OA studies should be well-defined intervention parameters, consistent documentation, and the use of appropriate patient-rated outcome measures.


Epitope-specific regulation and the literature.
The antibody response to a hapten conjugated to a protein can, in a number of situations, be suppressed by prior immunization with the carrier protein alone. The study of this finding appears to have been handicapped by previous literature on the subject having been consistently misquoted. It is to be hoped that recognition of this will allow a better understanding of the limitations to such suppression, and hence the mechanism by which it may act.


Processing and characterization of polyols plasticized-starch reinforced with microcrystalline cellulose.
Biocomposites suitable for short-life applications such as food packaging were prepared by melt processing and investigated. Biocomposites studied are wheat starch plasticized with two different molecular weight polyols (glycerol and sorbitol) and reinforced with various amounts of microcrystalline cellulose. The effect of the plasticizer type and the filler amount on the processing properties, the crystallization behavior and morphology developed for the materials, and the influence on thermal stability, dynamic mechanical properties and water absorption behavior were investigated. Addition of microcrystalline cellulose led to composites with good filler-matrix adhesion where the stiffness and resistance to humidity absorption were improved. The use of sorbitol as a plasticizer of starch also improved the stiffness and water uptake behavior of the material as well as its thermal stability. Biodegradable starch-based materials with a wide variety of properties can be tailored by varying the polyol plasticizer type and/or by adding microcrystalline cellulose filler.


A polygenic risk score analysis of ASD and ADHD across emotion recognition subtypes.
This study investigated the genetic components of ADHD and ASD by examining the cross-disorder trait of emotion recognition problems. The genetic burden for ADHD and ASD on previously identified emotion recognition factors (speed and accuracy of visual and auditory emotion recognition) and classes (Class 1: Average visual, impulsive auditory; Class 2: Average-strong visual & auditory; Class 3: Impulsive & imprecise visual, average auditory; Class 4: Weak visual & auditory) was assessed using ASD and ADHD polygenic risk scores (PRS). Our sample contained 552 participants: 74 with ADHD, 85 with ASD, 60 with ASD + ADHD, 177 unaffected siblings of ADHD or ASD probands, and 156 controls. ADHD- and ASD-PRS, calculated from the latest ADHD and ASD GWAS meta-analyses, were analyzed across these emotion recognition factors and classes using linear mixed models. Unexpectedly, the analysis of emotion recognition factors showed higher ASD-PRS to be associated with faster visual emotion recognition. The categorical analysis of emotion recognition classes showed ASD-PRS to be reduced in Class 3 compared to the other classes (p value threshold [pT] = 1, p = .021). A dimensional analysis identified a high ADHD-PRS reduced the probability of being assigned to the Class 1 or Class 3 (pT = .05, p = .028 and p = .044, respectively). Though these nominally significant results did not pass FDR correction, they potentially indicate different indirect causative chains from genetics via emotion recognition to ADHD and ASD, which need to be verified in future research.


Learning and Human Dignity Are Built Through Observation and Participation in Work.
This chapter focuses on how children learn through work in ongoing family and community endeavors in an Indigenous Mexican (Mixe) community, where cultural values emphasize that human dignity is derived from work and from collaboration with the work of other people, animals, and the natural world. The chapter highlights the central role that work plays in children's learning, and how attentive and more casual observation and accomplishment of endeavors are important tools that children employ in learning.


Increased incidence of teicoplanin-non-susceptible Staphylococcus epidermidis strains: a 6-year retrospective study.
Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis.


Analyzing tourism reviews using an LDA topic-based sentiment analysis approach.
It has become increasingly necessary to automate systems for organizing and classifying user reviews according to their domain-specific aspects and sentiment polarities, as online customer opinions have increased on specialized platforms and social networks. This study's methodology employs a combination of topic modeling and sentiment analysis, as well as human validation techniques of topic labels, to extract valuable insights about Marrakech city from TripAdvisor reviews. Through this technique, tourism practitioners and field specialists may dive deeper into online users generated content, leveraging aspect-based sentiment analysis to explore each destination's weaknesses and strengths.•Data collection and pre-processing.•Extracting latent topics using LDA algorithm (Latent Dirichlet Allocation) on collected reviews.•Applying sentiment analysis to each topic.


Effects of ticlopidine on metastasis production in mice bearing Lewis lung carcinoma.
Ticlopidine has been shown to markedly inhibit the platelet aggregability induced by ADP in control animals not receiving 3LL cells. Ticlopidine was administered orally at the selected dose (200 mg/kg/day), to the rodents using different dose schedules and the inhibitory effects on spontaneous lung metastases of the Lewis lung carcinoma were studied. Ticlopidine did not have any significant influence on the metastases formation and on the primary growth of 3LL, although it inhibited platelet aggregation in tumor-bearing mice. These data indicate that the antiaggregatory effects of ticlopidine are not related to an antimetastasic effect in our model.


Oxyberberrubine, a novel liver microsomes-mediated secondary metabolite of berberine, alleviates hyperuricemic nephropathy in mice.
Berberrubine (BRB), one of the major metabolites of berberine (BBR), exerts an anti-hyperuricemic effect even superior to BBR. Liver is an important location for drug transformation. Nevertheless, there are few studies on the bioactivities and metabolites of BRB. We investigated whether oxyberberrubine (OBR), a liver metabolite of BRB, exerted urate-lowering and reno-protective effects in hyperuricemic mice. Liver microsomes were used to incubate BRB for studying its biotransformation. We isolated and identified its new metabolite OBR, and investigated its anti-hyperuricemic and reno-protective effects. In this work, the hyperuricemic mice model was established by receiving potassium oxonate (PO) and hypoxanthine (HX) for 7 consecutive days. 1 h after modeling, different dosages of OBR (5, 10 and 20 mg/kg), BRB (20 mg/kg) or febuxostat (Fex, 5 mg/kg) were given mice by gavage. Results showed that OBR possessed potent anti-hyperuricemic and reno-protective effects in hyperuricemic mice. Serum uric acid (UA) level was lowered, and the activities of xanthine oxidase (XOD) as well as adenosine deaminase (ADA) in the liver were suppressed after treatment with OBR. Hepatic expressions of XOD were remarkably decreased at mRNA and protein levels by OBR treatment. In addition, OBR prominently alleviated renal injury, embodied in markedly reduced serum creatinine and blood urea nitrogen (BUN) levels, decreased inflammatory mediators (TNF-α, IL-1β, IL-6 and IL-18) levels, mRNA expression of CYP27B1 and repairment of renal tissues damage. Besides, OBR down-regulated renal expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 at mRNA and protein levels. In short, our study indicated that OBR possessed superior anti-hyperuricemic and reno-protective effects, at least in part, through the inhibition of XOD, URAT1, GLUT9 and NLRP3 inflammasome signaling pathway in the kidney.


Influence of copper content on NO removal of the activated carbon fibers produced by electroplating.
In this study, the activated carbon fibers (ACFs) on which copper metal was deposited by electroplating were used to remove nitric oxide (NO). N(2)/77 K adsorption isotherm characteristics, including the specific surface area and micropore volume, were investigated by BET and T-plot methods. NO removal efficiency was confirmed by gas chromatographic technique. From the experimental results, the copper content supported on ACFs led to an increase in the NO conversion, in spite of the decrease of the specific surface area or the micropore volume of ACFs. Consequently, the presence of Cu on ACFs played an important role in improving the NO reduction into O(2) and N(2), which was mainly attributed to the catalytic reactions of Cz-NO-Cu.


Rotational Three-dimensional OCTA: a Notable New Imaging Tool to Characterize Type 3 Macular Neovascularization.
This study explored whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding type 3 macular neovascularization (MNV). In this retrospective, cross-sectional study, we collected data from 15 eyes (13 patients) with treatment-naïve type 3 MNV in their post-nascent stage and age-related macular degeneration (AMD). Subjects were imaged with the SS-OCT system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a prototype volume projection removal algorithm and then analyzed using volumetric visualization techniques in order to obtain a 3D visualization of the region occupied by type 3 MNV. The two-dimensional and three-dimensional OCTA images were investigated. Mean ± SD age was 75.1 ± 7.4 years. BCVA was 0.42 ± 0.21 LogMAR in the study eyes. Considering the cohort of analyzed eyes, on rotational 3D OCTA images, a total of 35 neovascular lesions (vs 22 lesions detected on 2D OCTA images) rising from the deep vascular complex and variably spanning the outer retinal layers and eventually reaching the RPE/sub-RPE space were detected. Nine of 35 lesions had a saccular shape, while the remaining cases had a filiform shape. On rotational 3D OCTA images, these lesions were inclined on the three planes, instead of perpendicular to the RPE/Bruch's membrane. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of type 3 MNV. This approach seems to increase the detection rate for these lesions and to be useful to offer new insight into type 3 MNV.


Exhaled nitric oxide: relation to sensitization and respiratory symptoms.
Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation. To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross-sectional study of the respiratory health of bleachery workers. Two hundred and forty-six non-smoking bleachery and paper-mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop trade mark test. The atopic and the non-atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non-atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens. The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.


Lymphoma presenting with adrenal insufficiency. Adrenal enlargement on computed tomographic scanning as a clue to diagnosis.
A 73-year-old woman who presented with primary adrenal insufficiency and enlarged adrenal glands on computed tomographic scanning was ultimately found to have a large-cell lymphoma that had initially involved the adrenals and the stomach. A search of the English language medical literature revealed only seven other cases of lymphoma presenting with hypoadrenalism, none of which involved the stomach. As in this case, in most of those cases adrenal enlargement was documented on computed tomographic scanning. Despite its rare occurrence, lymphoma should be searched for in patients presenting with Addison's disease and enlarged adrenal glands.


The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD.
To assess the level of the suspiciousness in children with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) in comparison to ADHD alone and the response of suspiciousness symptoms to methylphenidate (MPH) treatment. In this open-label comparative study, children with DSM-IV-TR ADHD, aged 8-18 years, with (N = 30) or without (N = 30) ODD received MPH treatment for 12 weeks. The severity of ODD symptoms was assessed by the Kiddie-Schedule for Affective Disorders and Schizophrenia. The severity of ADHD symptoms was assessed by the ADHD-Rating-Scale-IV and suspiciousness was assessed at baseline and at endpoint by a scale designed especially for assessment of suspiciousness and named Suspiciousness Rating Scale (SRS). Significant reductions in SRS scores were detected in both groups following MPH treatment (before and after: p = .0012 and p = .0273, respectively). Only in the ADHD/ODD group a significant correlation was found between the rate of improvement in ADHD, as assessed by the ADHD-RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r = 0.48, p = .0066). In addition to the beneficial effect of MPH treatment on ADHD and ODD symptoms it also diminishes suspiciousness. However, due to the small sample size further studies are needed to confirm the present results.


Spontaneous pneumothorax in paediatric patients.
To obtain information to guide the management of children and early adolescents with apparent spontaneous pneumothorax the medical records of all patients over the age of 5 years presenting with this condition over a 25-yr period were reviewed. Twelve patients had a pneumothorax not associated with an acute episode of asthma. Six of these underwent thoracotomy at first presentation. Of the six who were initially treated conservatively five had a recurrence on the ipsilateral side. Seven patients developed a pneumothorax during an acute episode of asthma and none had a recurrence. Early intervention by either thoracotomy or some form of closed pleurodesis should be considered in paediatric patients presenting with an apparent spontaneous pneumothorax not associated with an acute episode of asthma. Pneumothorax complicating an acute episode of asthma is rare in the paediatric age group and is unlikely to recur.


Production of antibodies to Little cherry virus 1 coat protein by DNA prime and protein boost immunization.
Little cherry, an economically important disease of cherry is caused by at least two different viruses. One of these is Little cherry virus 1 (LChV-1) for the detection of which no efficient serological tools are available, so that diagnosis is based on molecular methods. In this study, different immunization strategies for producing antibodies against the viral coat protein of LChV-1 were tried, using either purified virus preparations, or bacterially expressed protein, or a DNA vector that expressed the cloned coat protein (CP) gene in vivo. Effective induction of specific antibodies to LChV-1 CP was obtained using DNA intramuscular immunization followed by a single boost with the recombinant protein. The entire coat protein sequence was cloned in a mammalian expression vector and, after being coated by an amphiphilic non-toxic reagent was delivered into rabbit. A protein boost increased the specific immune response against the virus protein. The sensitivity of this antiserum is lower if compared with that of antisera raised conventionally against other viruses, thus it requires improvements for use for diagnostic purposes.


Reproductive outcomes after floxuridine-based regimens for gestational trophoblastic neoplasia: A retrospective cohort study in a national referral center in China.
To analyze the reproductive outcomes of gestational trophoblastic neoplasia (GTN) patients who were cured only by floxuridine-based regimens. This was a retrospective analysis of 464 patients who were treated with only floxuridine-based regimens at Peking Union Medical College Hospital between January 2002 and December 2013 and retained their reproductive ability. Their reproductive outcomes were analyzed. The factors affecting pregnancy intention were identified by logistic regression. Of the 464 patients (average age, 28.0 ± 5.7 years; median follow-up = 85 months), the livebirth rate was 72.2%, while the rates of spontaneous abortion, induced abortion and ectopic pregnancy were 9.2% (n = 41), 8.7% (n = 39) and 1.8% (n = 8), respectively. The GTN recurrence rate was 2.1%. The time from chemotherapy completion to first conception in the induced abortion group was significantly shorter than those in spontaneous abortion, full-term/premature, and ectopic pregnancy groups (P ≤ 0.001, <0.001, =0.015, respectively). The logistic analysis showed that the age at onset of GTN (OR = 0.899, 95% CI 0.851-0.951, P < 0.001), parity at onset of GTN (parity = 1, OR = 0.123, 95% CI 0.068-0.225, P < 0.001; parity = 2-3, OR = 0.058, 95% CI 0.014-0.232, P < 0.001) and interval from the index pregnancy to chemotherapy were independent factors affecting pregnancy intention. Among the 36 pregnancies occurring within 12 months postchemotherapy, only one choriocarcinoma occurred, and 20 culminated in induced abortions (55.6%). After floxuridine-based chemotherapy, the pregnancy rate of GTN patients after fertility-preserving treatment is comparable to that of the normal population. Pregnancy losses within one year after chemotherapy completion are mainly caused by induced abortion.


Reliability, validity and ease of use of a portable point-of-care coagulation device in a pharmacist-managed anticoagulation clinic.
In a pharmacist-managed anticoagulation clinic, portable point-of-care coagulation devices may facilitate patient monitoring by providing rapid INR measurement. Few studies, however, have validated this type of device. To evaluate the reliability, validity and ease of use of the CoaguChek S, a new portable coagulation device. A total of 100 patients followed at a pharmacist-managed anticoagulation clinic attended two study visits. INRs were measured using the CoaguChek S and the standard laboratory technique. Reliability: The test-retest reliability (precision) of the CoaguChek S, estimated by the intraclass correlation coefficient (ICC) and a 95% confidence interval (95% CI), was high (0.98 (0.98-0.99)) and comparable to the standard laboratory technique (0.99 (0.98-0.99)). Interrater reliability was also high (0.97 (0.95-0.98)). Reliability coefficients did not vary with the test-strip lot number nor the CoaguChek S operator. When compared with standard laboratory procedure, the ICC (95% CI) was equal to 0.93 (0.91-0.95). The mean difference (95% CI) between INR measured by the laboratory and the CoaguChek S was equal to -0.02 units (-0.06-0.03). The mean absolute and relative absolute differences (95% CI) were equal to 0.24 units (0.21-0.27) and 9% (8%-10%), respectively. Differences tended to increase for INRs greater than 3 units as seen by a mean difference (95% CI) of -0.17 units (-0.35-0.02). This represented a mean absolute difference (95% CI) of 0.44 units (0.33-0.55) and a mean relative absolute difference of 12% (9%-15%). Concordance between therapeutic decisions based on CoaguChek S and laboratory results was high (Kappa = 0.68). In 34 cases (18%), the therapeutic decision would have been different. However, in 15 of these discordant observations, the difference between the CoaguCheck S and laboratory INR was <or=0.25 units. Ease of use: In 3% of cases, no INR could be measured by the CoaguChek S. The percentage of extra finger pricks and extra test-strips were equal to 25.8% and 23.7%, respectively. When used by health professionals in a pharmacist-managed anticoagulation clinic, the CoaguChek S is reliable, valid and easy to use. However, its validity tends to decrease as the INR increases, possibly due to the low sensitivity of the thromboplastin. If the CoaguChek S INR is supratherapeutic, we would therefore recommend confirming the results with a standard laboratory measurement.


STENCIL-NET for equation-free forecasting from data.
We present an artificial neural network architecture, termed STENCIL-NET, for equation-free forecasting of spatiotemporal dynamics from data. STENCIL-NET works by learning a discrete propagator that is able to reproduce the spatiotemporal dynamics of the training data. This data-driven propagator can then be used to forecast or extrapolate dynamics without needing to know a governing equation. STENCIL-NET does not learn a governing equation, nor an approximation to the data themselves. It instead learns a discrete propagator that reproduces the data. It therefore generalizes well to different dynamics and different grid resolutions. By analogy with classic numerical methods, we show that the discrete forecasting operators learned by STENCIL-NET are numerically stable and accurate for data represented on regular Cartesian grids. A once-trained STENCIL-NET model can be used for equation-free forecasting on larger spatial domains and for longer times than it was trained for, as an autonomous predictor of chaotic dynamics, as a coarse-graining method, and as a data-adaptive de-noising method, as we illustrate in numerical experiments. In all tests, STENCIL-NET generalizes better and is computationally more efficient, both in training and inference, than neural network architectures based on local (CNN) or global (FNO) nonlinear convolutions.


The BTA stat test is nonspecific for hematuria: an experimental hematuria model.
An experimental hematuria model was designed to determine whether the bladder tumor antigen (BTA) stat test (Bion Diagnostics, Redmond, Washington) is influenced by microscopic or macroscopic hematuria. A total of 25 healthy subjects provided urine and blood samples for the study. All subjects had a negative BTA stat test initially. Normal urine was mixed with autologous blood to cause hematuria of 3 degrees of severity. The test was performed in each sample after the creation of hematuria. BTA stat assay specificity in the presence of microscopic and gross hematuria was 80% and 24%, respectively. Results varied depending on the severity of hematuria, that is 20% for microscopic and 76% for gross hematuria. The results of the BTA stat test in the presence of microscopic hematuria must be interpreted in regard to the degree of hematuria. The test is not reliable in urine samples with gross hematuria due to a high false-positive rate.


Antibody signatures defined by high-content peptide microarray analysis.
Circulating antibodies are highly selective binding reagents directed to a vast repertoire of antigens. Candidate antigens displayed as overlapping peptides on microarrays can be used to screen for recognition by serum antibodies from clinically well-defined patient populations. The methodology is robust and enables unbiased visualization of antigen-specific B-cell responses. Additionally, autoantibody signatures of diagnostic value could be detected using microarrays displaying thousands of human peptides.


Phase II trial on neoadjuvant intravenous and trans-uterine arterial chemotherapy for locally advanced bulky cervical adenocarcinoma.
A phase II trial on neoadjuvant trans-uterine arterial chemotherapy (TUAC) followed by type III radical hysterectomy (RH) was conducted for patients with bulky cervical adenocarcinoma (AC). Tumors of >4 cm were eligible. The neoadjuvant regimen comprised paclitaxel (60 mg/m(2) intravenously on days 1, 8, and 15) and cisplatin (70 mg/m(2) TUAC followed by transcatheter embolization with gelatin sponge particles on day 2) repeated every 3 weeks for 3 cycles. The primary endpoints were clinical and pathological responses. Twenty-two patients (median age, 51 years; range, 33-75 years) were enrolled. The International Federation of Gynecology and Obstetrics stages were IB2 (9 patients), IIA-IIB (8), IIIB (3), and IVA (2). The adeno/adenosquamous ratio was 16/6. The overall clinical response rate was 95.4% (95% confidence interval [CI], 86.7-100%). RH was completed in 19 patients (86%), including 2 stage IVA patients who underwent anterior or posterior pelvic exenteration. Of the 19 patients, no residual malignant cells were found pathologically in 4; thus, the pathological complete response rate was 18% (4/22). No patients experienced grade 4 thrombocytopenia or febrile neutropenia or required platelet transfusions. The 5-year progression-free survival and overall survival rates in stages IB2-IIB were 70.0% (95%CI, 48.1-92.1%) and 69.5% (95%CI, 47.0-92.0%), respectively. The 2 patients with stage IVA tumors were alive without recurrence for 72 and 84 months after enrollment. TUAC showed high clinical and pathological response rates. TUAC is promising for stage IB2-IIB and IVA bulky AC.


IVF outcome in poor responders failing to produce viable embryos in the preceding cycle.
This study postulated that poor-responder women failing to obtain viable embryos would represent a subgroup of subjects with extremely poor prognosis. To elucidate this aspect, women in this condition over a 4-year period were retrospectively identified and their IVF outcomes in subsequent cycles were evaluated. A total of 108 women satisfied the selection criteria and underwent at least one further IVF cycle. There were 19 women excluded because they opted for a mild approach using clomiphene citrate alone, leaving 89 women for data analyses. Four women had a live birth during this first cycle, corresponding to a delivery rate per started cycle of 4.5% (95% CI 1.5-10.0%). From a public health perspective, the mean cost per delivery was € 124,540. Younger age emerged as the unique predictive factor of success. In conclusion, women with poor ovarian response failing to obtain viable embryos have extremely low chances of success in subsequent cycles. Considering the costs and risks of IVF, the appropriateness of pursuing treatments in these women is questionable. Younger women may represent a possible exception since their chances of delivery are higher.


Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family.
Elafin and SLPI are low-molecular weight proteins that were first identified as protease inhibitors in mucous fluids including lung secretions, where they help control excessive proteolysis due to neutrophil serine proteases (elastase, proteinase 3 and cathepsin G). Elafin and SLPI are structurally related in that both have a fold with a four-disulfide core or whey acidic protein (WAP) domain responsible for inhibiting proteases. Elafin is derived from a precursor, trappin-2 or pre-elafin, by proteolysis. Trappin-2, which is itself a protease inhibitor, has a unique N-terminal domain that enables it to become cross-linked to extracellular matrix proteins by transglutaminase(s). SLPI and elafin/trappin-2 are attractive candidates as therapeutic molecules for inhibiting neutrophil serine proteases in inflammatory lung diseases. Hence, they have become the WAP proteins most studied over the last decade. This review focuses on recent findings revealing that SLPI and elafin/trappin-2 have many biological functions as diverse as anti-bacterial, anti-fungal, anti-viral, anti-inflammatory and immuno-modulatory functions, in addition to their well-recognized role as protease inhibitors.


Activity of bromochlorodifluoromethane (BCF) in three mutation tests.
The halocarbon BCF was tested in 3 assays to assess its mutagenicity and clastogenicity. It produced a positive response in Salmonella typhimurium strain TA1535 but was negative in TA1537, TA1538, TA98 and TA100. In an L5178Y mouse lymphoma microwell assay (TK locus), BCF was negative. BCF was administered at 5000 and 50 000 ppm in air for 6 h to groups of C57B1/6J mice of both sexes. Animals were killed at 24, 48 and 72 h after cessation of exposure and the incidence of bone marrow micronuclei per 1000 PCEs determined. There was no significant difference in the incidences of micronuclei between untreated animals and those exposed to either concentration of BCF at any of the sampling times. These results suggest that BCF is mutagenic in vitro in only one strain of Salmonella; in mammalian cells the compound induced no gene mutation in vitro nor clastogenic activity in vivo at doses that also produced clear evidence of toxicity.


A randomized controlled clinical trial to improve health outcomes in youth with type 1 diabetes: Study design and baseline characteristics.
Most adolescents with T1D do not meet glycemic recommendations or consistently perform the required self-management behaviors to prevent acute- and long-term deleterious health outcomes. In addition, most youth with T1D do not have access to behavioral health services to address T1D management barriers. Thus, delivering behavioral interventions during routine medical appointments may hold promise for improving T1D outcomes in adolescents. The overall objective of this study was to examine the effect of behavioral interventions, either a Personalized T1D Self-Management Behaviors Feedback Report or Problem-Solving Skills, delivered by a T1D behavioral health provider and a T1D medical provider during a joint, fully integrated appointment to improve health outcomes in youth with T1D. This paper describes the study rationale, design, and baseline characteristics for the 109 adolescent-caregiver dyads who participated. Primary and secondary outcomes include hemoglobin A1c (A1C), T1D self-management behaviors, and biological indicators of complications.


Obesity related to metabolic syndrome: comparison of obesity indicators in an older french population.
Metabolic syndrome (MS) represents a cluster of metabolic abnormalities. Insulin resistance is a major component of the syndrome. We analyze in this study the relationship between body fat composition and MS in comparison to usual obesity indicators in an older adult population. The PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) study is a prospective longitudinal community cohort study among the inhabitants of Saint-Etienne, France. The study is a cohort study of 1011 subjects, mean age 65.6 ± 0.8 years old at inclusion, recruited from the electoral list of the town in 2000. Among them, 806 subjects realized a Dual-energy X-ray absorptiometry (DXA) used to evaluate body fat and lean mass repartition. We evaluate biological metabolic parameters according to usual techniques. The indices of obesity were calculated according to standard formula. MS presence and its components were simultaneously evaluated. All obesity parameters were significantly higher (p < 0.0001) in subjects suffering metabolic syndrome as compared to those without. Body fat index (BFI) presented a stronger correlation to total fat mass, trunk fat mass and body adiposity index (BAI). The correlations between body indices and metabolic components showed that body mass index (BMI) and waist circumference were more strongly associated with BFI as compared to BAI and total fat mass. According to logistic regression analysis, only the waist-hip ratio (WHR) demonstrated a significant association with MS severity (p < 0.0001). Among the obesity indices, BFI and BAI represented the best indicators to characterize global obesity while WHR only is highly predictive of metabolic syndrome presence and severity. The BAI indicator is an alternative for measuring obesity. Comparison of long-term impact of such markers on cardiovascular morbidity and mortality is now questioned.


Household Water Is the Main Source of Iodine Consumption among Women in Hargeisa, Somaliland: A Cross-Sectional Study.
Iodine status surveys of women in Somaliland present widely conflicting results. Previous research indicates elevated concentrations of iodine (IQR 18-72 μg/L) in groundwater used for drinking and cooking, but the relation with iodine intake is not well characterized. We aimed to investigate the contributions of household water iodine concentration (WIC), breastfeeding, total fluid intake, hydration levels, and urine volume on urinary iodine concentration (UIC) and excretion (UIE) over a 24-h period and to define iodine status from iodine intake estimates and median UIC, normalized to a mean urine volume of 1.38 L/d (hydration adjusted). The study sample comprised 118 nonpregnant, healthy women aged 15-69 y. All participants resided in Hargeisa, and 27 were breastfeeding. Data collection consisted of a 24-h urine collection, a 24-h fluid intake diary, a beverage frequency questionnaire, and a structured recall interview. We measured UIC and WIC in all urine and in 49 household water samples using the Sandell-Kolthoff reaction. WIC ranged between 3 and 188 μg/L, with significant median differences across the water sources and city districts (P < 0.003). Nonbreastfeeding women were borderline iodine sufficient [hydration-adjusted median urinary iodine concentration (mUIC) 109 μg/L; 95% CI: 97, 121 μg/L], whereas breastfeeding women showed a mild iodine deficiency (73 μg/L; 95% CI: 54, 90 μg/L). There were strong correlations (ρ: 0.50-0.69, P = 0.001) between WIC and UIC, with iodine from household water contributing more than one-half of the total iodine intake. Multivariate regression showed hydration and breastfeeding status to be the main predictors of UIC. Iodine from household water is the main contributor to total iodine intake among women in Hargeisa, Somaliland. Variation in female hydration and spatial and temporal WIC may explain diverging mUIC between studies. Water sources at the extremes of low and high iodine concentrations increase the risk of subpopulations with insufficient or more than adequate iodine intake.


Acousto-microfluidics for screening of ssDNA aptamer.
We demonstrate a new screening method for obtaining a prostate-specific antigen (PSA) binding aptamer based on an acoustofluidic separation (acoustophoreis) technique. Since acoustophoresis provides simultaneous washing and separation in a continuous flow mode, we efficiently obtained a PSA binding aptamer that shows high affinity without any additional washing step, which is necessary in other screening methods. In addition, next-generation sequencing (NGS) was applied to accelerate the identification of the screened ssDNA pool, improving the selecting process of the aptamer candidate based on the frequency ranking of the sequences. After the 8(th) round of the acoustophoretic systematic evolution of ligands by exponential enrichment (SELEX) and following sequence analysis with NGS, 7 PSA binding ssDNA aptamer-candidates were obtained and characterized with surface plasmon resonance (SPR) for affinity and specificity. As a result of the new SELEX method with PSA as the model target protein, the best PSA binding aptamer showed specific binding to PSA with a dissociation constant (Kd) of 0.7 nM.


The current status of zoonotic leishmaniases and approaches to disease control.
Leishmaniases are a complex of world-wide diseases with a range of clinical and epidemiological features caused by Leishmania spp. of protozoan parasites. Among 15 well-recognised Leishmania species known to infect humans, 13 have zoonotic nature, which include agents of visceral, cutaneous and mucocutaneous forms of the disease in both the Old and New Worlds. Currently, leishmaniases show a wider geographic distribution and increased global incidence of human disease than previously known. Environmental, demographic and human behavioural factors contribute to the changing landscape of leishmaniasis, which includes increasing risk factors for zoonotic cutaneous leishmaniases and new scenarios associated with the zoonotic visceral leishmaniases. The latter consist of the northward spread of Leishmania infantum transmission in Europe and America, the identification of unusual mammal hosts, and the decline of HIV-Leishmania co-infections in southern Europe following the introduction of the highly active antiretroviral therapy. Few advances have been made in the surveillance and control of the zoonotic leishmaniasis, however a number of tools have been developed for the control of the canine reservoir of L. infantum. These include: (i) several canine vaccine candidates, in particular an FML Leishmania enriched fraction showing good clinical protection, has been registered in Brazil for veterinary use; (ii) a number of insecticide-based preparations have been specifically registered for dog protection against sand fly bites. Laboratory and field studies have shown improved efficacy of these preparations for both individual and mass protection.


A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation.
The early stages of Alzheimer's disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future pathological tau accumulation. In particular, we use machine learning to quantify interactions between key pathological markers (β-amyloid, medial temporal lobe atrophy, tau and APOE 4) at mildly impaired and asymptomatic stages of AD. Using baseline non-tau markers we derive a prognostic index that: (a) stratifies patients based on future pathological tau accumulation, (b) predicts individualised regional future rate of tau accumulation, and (c) translates predictions from deep phenotyping patient cohorts to cognitively normal individuals. Our results propose a robust approach for fine scale stratification and prognostication with translation impact for clinical trial design targeting the earliest stages of AD.


Reductive dechlorination of octachlorodibenzo-p-dioxin by nanosized zero-valent zinc: modeling of rate kinetics and congener profile.
Polychlorinated dibenzo-p-dioxins (PCDDs), a group of recalcitrant toxic compounds, are ubiquitous in nature. Amongst them, octachlorodibenzo-p-dioxin (OCDD) is not only prevalent in soil and sediment due to its high lipophilicity and hydrophobicity, but also detected in ground water and surface water. The present study examined the degradation of OCDD in aqueous solutions using four different zero-valent metal nanoparticles; zero-valent aluminum (nZVAL), zero-valent zinc (nZVZ), zero-valent iron (nZVI) and zero-valent nickel (nZVN). Only nZVZ was found to efficiently degrade OCDD into lower chlorinated congeners [OCDD → 1,2,3,4,6,7,9-HxCDD (63%)→ 1,2,3,6,8,9-HpCDD (21%) → 1,2,4,7,8-PeCDD (46%) → 1,2,4,7-TeCDD (19%)] under ambient conditions. Simulations were also performed to predict the OCDD dechlorination pathway using a linear free energy relationship (LFER) model. Additionally, toxic equivalent quantity (TEQ) and homologue patterns were calculated by LFER modeling. The experimentally observed congener profiles were in excellent agreement with the model-predicted results, especially considering the complexity of the OCDD dechlorination pathway (256 theoretically possible reactions). This study proposes nZVZ as a suitable candidate for OCDD dechlorination and constitutes the first report on OCDD degradation using zero-valent metal nanoparticles under ambient conditions.


Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi.
Phosphatidylinositol 4 phosphate [PI(4)P] is essential for secretion in yeast, but its role in mammalian cells is unclear. Current paradigms propose that PI(4)P acts primarily as a precursor to phosphatidylinositol 4,5 bisphosphate (PIP2), an important plasma membrane regulator. We found that PI(4)P is enriched in the mammalian Golgi, and used RNA interference (RNAi) of PI4KIIalpha, a Golgi resident phosphatidylinositol 4 kinase, to determine whether PI(4)P directly regulates the Golgi. PI4KIIalpha RNAi decreases Golgi PI(4)P, blocks the recruitment of clathrin adaptor AP-1 complexes to the Golgi, and inhibits AP-1-dependent functions. This AP-1 binding defect is rescued by adding back PI(4)P. In addition, purified AP-1 binds PI(4)P, and anti-PI(4)P inhibits the in vitro recruitment of cytosolic AP-1 to normal cellular membranes. We propose that PI4KIIalpha establishes the Golgi's unique lipid-defined organelle identity by generating PI(4)P-rich domains that specify the docking of the AP-1 coat machinery.


Initial experience with extracorporeal shock wave lithotripsy in children.
The clinical experience is presented of 4 United States centers at which extracorporeal shock wave lithotripsy was used for the treatment of renal calculi in 38 children 12 months to 16 years old. Patient characteristics, treatment specifics and followup data are detailed. Complete fragmentation of calculi was obtained in 97 per cent of those treated, with a 5 per cent complication rate. This experience demonstrates that with proper safeguards, extracorporeal shock wave lithotripsy can be performed safely and effectively in the pediatric population.


Modulatory effects of type-C natriuretic peptide on sympathetic cotransmission in the rat isolated tail artery.
1. Rat type-C natriuretic peptide (CNP) has been studied for its effects on the neurogenically induced overflow of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), adenosine (ADO) and noradrenaline (NA) in endothelium-free segments of rat isolated tail artery. The overflow of each was evoked by electrical field stimulation (EFS) of 0.5 ms pulses at 8 Hz for 3 min and the amount of ATP, ADP, AMP and ADO was quantified by high-performance liquid chromatography (HPLC)-fluorescent detection, while the amount of NA was quantified by HPLC-electrochemical detection. 2. Type-C natriuretic peptide (100 nmol/L) was found to cause a significant reduction of the overflow of all adenine purines and NA. However, at lower concentrations (1 and 10 nmol/L), CNP caused a significant reduction of the overflow of NA but did not change ATP overflow. 3. The overflow of ADP, AMP and ADO was significantly reduced by either concentration of CNP, so that the ratio ATP:ADP was diminished from 1:2 in controls to 1:1 after 1 nmol/L CNP and to 1:1.2 after 10 nmol/L CNP. 4. The production of inorganic phosphate (Pi) in response to the exogenous application of ATP was significantly reduced by 1, 10 or 100 nmol/L CNP. 5. Type-C natriuretic peptide exerts neuromodulatory effects on the neurogenically induced release of the cotransmitters ATP and NA in rat tail artery, consisting of an inhibition of the release of both ATP and NA. This effect is accompanied by inhibition of the breakdown of ATP by ecto-ATPases. Either effect results in apparent CNP-induced differential modulation of the overflow of the cotransmitters ATP and NA.


Qualitative aspects of hydrogen-deuterium exchange in the 1H, 13C, and 15N nuclear magnetic resonance spectra of viomycin in aqueous solution.
The 1H, 13C, and 15N high field nuclear magnetic resonance spectra of the cyclic peptide viomycin have been fully assigned using homo- and heteronuclear double resonance experiments and pH effects. In addition it is shown how the two- and three-bond H-D isotope effects upon carbonyl resonances may assist in their assignment. The resistance to exchange with solvent water of the amide proton involved in the transannular hydrogen bond is observed directly in the 1H spectra, via the isotope effect on a carbonyl resonance in the 13C spectra, and via the one-bond 1H couppling in the 15N spectra.


Manganese superoxide dismutase (MnSOD) is a malignant astrocytoma specific biomarker and associated with adverse prognosis in p53 expressing glioblastoma.
Manganese super oxide dismutase (MnSOD) has been previously identified as one of the top regulated genes associated with poor survival in glioblastoma (GBM) patients. In the current study we have evaluated the protein expression of MnSOD across various grades of astrocytoma, studied its influence on survival of GBM patients and following recurrence. The protein expression of MnSOD was analyzed on tumor tissue sections by immunohistochemistry on 30 diffuse astrocytomas (DA), 50 anaplastic astrocytomas (AA), 30 paired (primary and recurrent) GBM samples and 30 non-tumor brain tissues. The protein expression among the different grades of diffusely infiltrating astrocytoma (DIA) was evaluated by Kruskal-Wallis one-way ANOVA followed by post hoc test. Wilcoxon matched pair test was employed to assess MnSOD protein expression across 30 paired GBM samples (primary and recurrent). The prognostic impact of MnSOD protein expression individually and following stratification with p53 expression was evaluated in a cohort of 123 GBM patients. Both over-all survival (OS) and progression free survival (PFS) analysis were performed by employing Cox regression analysis and Kaplan-Meier survival analysis on GBM patients. A significantly increased protein expression of MnSOD was observed among malignant astrocytomas (GBM and AA) in comparison with either DA or non-tumor brain tissues (p<0.05). Among the GBM cases it was noted that the IDH1 immunopositive tumors (R132H mutant protein; n=17) had a low MnSOD expression as opposed to IDH1 immunonegative tumors (n=106), which had high expression of MnSOD (p=0.0307). Further, a statistically significant increase (p=0.010) in extent of MnSOD protein expression was also noted in GBM tumors following recurrence. Protein expression of MnSOD was associated with both poor OS (HR: 1.021; p=0.011) and early PFS (HR: 1.022; p=0.006) on univariate analysis. Multivariate Cox regression analysis as well as Kaplan-Meier survival analysis demonstrated similar poor prognostic association. Stratification of GBM cases based on p53 expression status revealed a strong association of MnSOD with OS (HR: 1.042; p=0.002) and PFS (HR: 1.044; p=0.001) in p53 positive tumor tissue samples. Similar findings were noted on multivariate Cox regression analysis and K-M survival analysis, while no such association was noted in tumor tissues staining negative for p53 expression. Our study shows an increased expression of MnSOD in anaplastic astrocytoma and GBM compared to low grade astrocytoma and control brain. An increase in MnSOD expression following GBM tumor recurrence strengthens its putative role in tumor aggressiveness. Further, MnSOD emerges as a poor prognostic biomarker in p53 expressing GBMs, rendering this molecule as a potential therapeutic target in such patients.


Neuro-otological abnormalities in xeroderma pigmentosum with particular reference to deafness.
The neuro-otological findings are described in 3 unrelated patients who had xeroderma pigmentosum. All had impaired hearing. Routine audiometric assessment suggested that the hearing loss was of cochlear origin; brainstem evoked potentials in 2 patients and electrocochleography in 1 support this conclusion. Two adult patients had a supranuclear ophthalmoplegia. Vestibular function was mildly deranged and visual suppression of the vestibulo-ocular reflex impaired.


Effects of the cyanobacterium Cylindrospermopsis raciborskii on feeding and life-history characteristics of the grazer Daphnia magna.
Laboratory experiments were used to test the hypothesis that feeding and growth of the zooplankton grazer Daphnia magna will decrease with increasing proportions of the cyanobacterium Cylindrospermopsis raciborskii in the diet (mixed feeds with the green alga Scenedesmus obliquus). A strain of C. raciborskii, which does not produce cylindrospermopsin but contains saxitoxins and gonyautoxins, was not acutely toxic to Daphnia, as the daphnids survived slightly longer in suspensions with the cyanobacterium as the sole feed than in medium without food. Daphnia growth rates were only depressed at feeds comprised of 75% C. raciborskii or more. Daphnids were larger with increased proportions of Scenedesmus in the food, but there was no difference between animals reared on mixed feeds and those grown on different proportions of a pure diet of Scenedesmus. Daphnia clearance rates on feeds with a high share of C. raciborskii were significantly lower than on mixtures with a low share of C. raciborskii. Consequently, in cylindrospermopsin-free strains, chemotypes that have been observed so far in Europe and Brazil, feeding inhibition and the resulting energy limitation might be the dominant factor affecting growth of large-bodied cladocerans.


In vivo imaging of brain metabolism activity using a phosphorescent oxygen-sensitive probe.
Several approaches have been adopted for real-time imaging of neural activity in vivo. We tested a new cell-penetrating phosphorescent oxygen-sensitive probe, NanO2-IR, to monitor temporal and spatial dynamics of oxygen metabolism in the neocortex following peripheral sensory stimulation. Probe solution was applied to the surface of anesthetized mouse brain; optical imaging was performed using a MiCAM-02 system. Trains of whisker stimuli were delivered and associated changes in phosphorescent signal were recorded in the contralateral somatosensory ("barrel") cortex. Sensory stimulation led to changes in oxygenation of activated areas of the barrel cortex. The oxygen imaging results were compared to those produced by the voltage-sensitive dye RH-1691. While the signals emitted by the two probes differed in shape and amplitude, they both faithfully indicated specific whisker evoked cortical activity. Thus, NanO2-IR probe can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo.


It's not age that prevents sexual activity later in life.
To describe key factors that facilitate sexual behaviour in later life. Re-analysis of data from a study of 2,374 Dutch older adults. Partner availability, gender and health are likely to be more important factors influencing sexual behaviour engagement than the factor of age in later life. Lack of partner availability, traditional gender roles and poor health are associated with older age. However, current generations of older adults will be more capable, less ashamed of their sexual desires and engage in more sexual behaviour than prior generations. This analysis observed that sexual activity is associated with partner availability and better health, rather than age, countering stereotypes of decline in sexual behaviour and normalising sexual activity and desire in later life.


The Fabrication of Flow Field Plates for Direct Methanol Fuel Cell Using Lithography and Radio Frequency Sputtering.
This study uses lithography to etch flow fields on a single side of a printed circuit board (PCB) and combines a flow field plate with a collector plate to make innovative anode flow field plates and cathode flow field plates for a direct methanol fuel cell (DMFC). TiO2 thin film is also sputtered on the anode flow field plate using radio frequency (RF) sputtering. The experimental results show that the prepared DMFC has a better maximum power density of 11.928 mW/cm2. Furthermore, when a TiO2 thin film is sputtered on the flow field plate of the assembled DMFC, the maximum power density is 14.426 mW/cm2, which is actually 21% more than that for a DMFC with no TiO2 thin film coated on the flow field plate.


The clinical potential of GDF15 as a "ready-to-feed indicator" for critically ill adults.
Circulating growth-differentiation factor-15 (GDF15), a cellular stress marker, abruptly increases during critical illness, but its later time course remains unclear. GDF15 physiologically controls oral intake by driving aversive responses to nutrition. Early parenteral nutrition (PN) in ICU patients has overall been shown not beneficial. We hypothesized that low GDF15 can identify patients who benefit from early PN, tolerate enteral nutrition (EN), and resume spontaneous oral intake. In secondary analyses of the EPaNIC-RCT on timing of PN initiation (early PN versus late PN) and the prospective observational DAS study, we documented the time course of circulating GDF15 in ICU (N = 1128) and 1 week post-ICU (N = 72), compared with healthy subjects (N = 65), and the impact hereon of randomization to early PN versus late PN in propensity score-matched groups (N = 564/group). Interaction between upon-admission GDF15 and randomization for its outcome effects was investigated (N = 4393). Finally, association between GDF15 and EN tolerance in ICU (N = 1383) and oral intake beyond ICU discharge (N = 72) was studied. GDF15 was elevated throughout ICU stay, similarly in early PN and late PN patients, and remained high beyond ICU discharge (p < 0.0001). Upon-admission GDF15 did not interact with randomization to early PN versus late PN for its outcome effects, but higher GDF15 independently related to worse outcomes (p ≤ 0.002). Lower GDF15 was only weakly related to gastrointestinal tolerance (p < 0.0001) and a steeper drop in GDF15 with more oral intake after ICU discharge (p = 0.05). In critically ill patients, high GDF15 reflected poor prognosis and may contribute to aversive responses to nutrition. However, the potential of GDF15 as "ready-to-feed indicator" appears limited. ClinicalTrials.gov , NCT00512122, registered 31 July 2007, https://www.clinicaltrials.gov/ct2/show/NCT00512122 (EPaNIC trial) and ISRCTN, ISRCTN 98806770, registered 11 November 2014, http://www.isrctn.com/ISRCTN98806770 (DAS trial).


Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.
Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure. Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS). The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.


Seed size: phylogeny and adaptation in two closely related Proteaceae species-pairs.
We studied seed size, seed nutrient status and seedling growth of two closely related fynbos Proteaceae species-pairs growing on juxtaposed soils of different nutrient and moisture status. Seeds had a greater mass and higher phosphorus and nitrogen contents for species occurring on limestone (higher nutrient and moisture contents) than those on the colluvial sands (lower nutreints and moisture). This trend was found within, but not across genera, stressing the importance of phylogeny in interpreting adaptations. It would be difficult to test for the effects of either nutrients or moisture separately, since the same advantage of enhanced seedling size, and hence survival in a stressed environment, applies to both factors. The increased root: shoot ratios (using lengths) of the Leucadendron species relative to the Protea species are interpreted as an attempt to overcome a phylogenetic constraint that results in smaller seed size in the former genus.


Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.
Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Therapeutic cross-over study. Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and without metformin, before and after induction of IR with dexamethasone. Metformin was administered by nasogastric tube at 30 mg/kg bwt 1 h before administration of dextrose. Glucose and insulin concentrations in plasma/serum were measured at regular intervals during each test. Linear mixed models were specified for each predetermined outcome variable, and for each model the 'treatment' was included as a fixed effect with 4 categorical levels (none, metformin, dexamethasone and dexamethasone with metformin) and horse accounted for as a random effect. In healthy horses, the administration of metformin resulted in a statistically significant reduction in peak glucose concentration (P = 0.002), area under the glucose curve (P<0.001) and insulin concentration 120 min after dextrose administration (P = 0.011). Following the induction of IR, administration of metformin was associated with significant differences in peak glucose concentration (P<0.001), the percentage increase in glucose concentration (P = 0.010), the area under the glucose curve (P<0.001) and insulin concentration at 120 min (P = 0.034) and 150 min after dextrose administration (P = 0.014). Metformin resulted in reduced glycaemic and insulinaemic responses both in healthy horses and in horses with experimentally induced IR. Metformin may benefit horses with naturally acquired IR by reducing glycaemic and insulinaemic responses to dietary nonstructural carbohydrates. Further investigations into the mechanisms of action of metformin in horses and controlled clinical trials are warranted.


VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations.
The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. Lack of VEGF-D resulted in long-term memory deficits, suggesting a link between dendritic morphology and cognitive function. Here, we compared the effect of VEGF-D expression on basal versus apical dendrites of CA1 pyramidal cells, as well as its importance for synaptic processing of network oscillations. We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.


Molecular dissection of a putative iron reductase from Desulfotomaculum reducens MI-1.
Desulfotomaculum reducens MI-1 is a Firmicute strain capable of reducing a variety of heavy metal ions and has a great potential in heavy metal bioremediation. We recently identified Dred_2421 as a potential iron reductase through proteomic study of D. reducens. The current study examines its iron-reduction mechanism. Dred_2421, like its close homolog from Escherichia coli (2, 4-dienoyl-CoA reductase), has an FMN-binding N-terminal domain (NTD), an FAD-binding C-terminal domain (CTD), and a 4Fe-4S cluster between the two domains. To understand the mechanism of the iron-reduction activity and the role of each domain, we generated a series of variants for each domain and investigated their iron-reduction activity. Our results suggest that CTD is the main contributor of the iron-reduction activity, and that NTD and the 4Fe-4S cluster are not directly involved in such activity. This study provides a mechanistic understanding of the iron-reductase activity of Dred_2421 and may also help to elucidate other physiological activities this enzyme may have.


Identification of DNA aptamers that specifically targets EBV+ nasopharyngeal carcinoma via binding with EphA2/CD98hc complex.
Nasopharyngeal carcinoma (NPC) is one of the Epstein-Barr virus (EBV)-associated malignancies and has a distinct geographical distribution. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for biomarkers for early diagnosis and effective treatments. In this study, we developed DNA aptamers that specifically bind to EBV positive NPC cells by the Cell-SELEX procedure. We further identified the EphA2 (ephrin type-A receptor 2)/CD98hc (CD98 heavy chain) complex as the potential target of the aptamer EA-3 by combining aptamer-based separation and mass spectrometry analysis. Our results revealed for the first time that EphA2 colocalized with CD98hc at the plasma membrane and EphA2 coimmunoprecipitated with CD98hc, which may serve as a starting point for exploring the potential functions of the complex of EphA2 and CD98hc in NPCs. Here, we demonstrated that aptamers can be useful for the identification of protein complexes on the surface of cancer cells.


[Value of compression and change of posture of patients in the gastroduodenal double contrast technique].
The authors perform the upper gastrointestinal examination in order to demonstrate lesions that would not be seen by other radiologic techniques. Due to the progress of Endoscopy in the last years, it is necessary a detailed radiologic examination to reach the diagnostic possibilities that the former did. A good help to do that is the compression in prone dedecubitus with inflatable balloon and the patient's mobilization under radioscopic control.


The Sagittal Thoracic Modifier Component of the Lenke Classification System in Moderate and Severe Adolescent Idiopathic Scoliosis: Reliability and Reproducibility of Measurements Among 5 Observers.
A prospective radiographic study. As the importance of the spinal sagittal profile becomes increasingly evident, there is a need to ensure that the measuring methods used to evaluate thoracic kyphosis (TK) are both accurate and reproducible. The purpose of the following study was to determine the intraobserver and interobserver variability of measurements of the sagittal profile in moderate and severe thoracic scoliosis. Five experienced Faculty Spine surgeons independently reviewed thirty standing long 30-inch cassette lateral radiographs of preoperative moderate and severe curves ≥50 degrees of adolescent idiopathic scoliosis (AIS) patients on 2 different occasions. The parameters measured were the vertebral endplate clarity and measurability of the sagittal angle from D5 to D12 and categories of thoracic sagittal modifier. κ statistics and Intraclass Correlation Coefficient (ICC) were used for analysis. The interobserver percentage of agreement for the Sagittal modifier was 58% in both trials. The mean κ coefficient value was only moderate 0.43 (range, 0.14-0.66) for both trials. The number of the vertebral endplates that were difficult to identify was 201 of 300 measurements (67%). There was a predominance of difficulty to identify vertebral endplate clarity in all curve types. The results of this study yielded poor to moderate interobserver reliability of the thoracic sagittal profile component of the Lenke classification system in moderate and severe AIS. This was attributed to the difficulty in identification of the vertebral endplates. The current standard lateral radiographs routinely used in AIS patients have inherent difficulties and limitations to visualize, identify, and analyze the thoracic endplates in moderate and severe curves.


'Personalizing' shorter regimens: Need of the hour.
The launch of injectable shorter regimens under Programmatic Management of Drug Resistant Tuberculosis (PMDT) guidelines 2017 under Revised National Tuberculosis Control Program (RNTCP) was a welcome step as it decreased the duration of treatment significantly in Drug Resistant Tuberculosis (DRTB) patients. The objective of the present study was to evaluate the treatment outcomes of patients started on injectable shorter regimens from March 2018 to May, 2019. Retrospective study which scrutinized medical records of 85 patients started on injectable shorter regimen was conducted. Necessary information on possible patient and disease related predicting factors like age, gender, weight, HIV status, presence of diabetes mellitus (DM), anemia, gap between diagnosis and initiation of treatment, duration of intensive phase (IP) and time of sputum conversion was retrieved, and analyzed for possible association with treatment outcomes. 56.5% had successful treatment outcomes. Age, gender, BMI, diabetic/anemic status and gap between diagnosis and initiation of treatment had no statistically significant relationship with the final outcomes. Duration of IP, sputum conversion and time of outcome during the course of illness emerged as significant factors in successful outcomes. The injectable shorter regimens were suitable for a variety of population irrespective of demographic disparities. Patients need to be followed closely as microbiological parameters serve as early indicators of unsuccessful outcomes. These regimens can serve as an alternate choice in patients not tolerating the all oral shorter Bedaquiline containing shorter regimen. Similar such options with combinations of different drugs for individualizing treatment regimens is the need of the hour.


Seed yield, seed size and germination behaviour in the annualPogogyne abramsii.
Models of the evolution of seed dormancy reveal that dormancy is favoured either when opportunities for establishment vary over time and when there is wide variation in the probability of success, or when the probability of success is limited by frequency dependence. Empirical evidence supporting the temporal heterogeneity hypothesis exists, but there is scant evidence for dormancy being favoured by frequency dependent competition among seedlings. We test the hypothesis that the intensity of between-sib competition should favour a positive relationship between maternal fecundity and seed dormancy. This hypothesis is supported for the rare, vernal pool annual,Pogogyne abramsii: the proportion of dormant offspring was significantly higher among high fecundity mothers than among other mothers. Dormancy inP. abramsii is controlled by the seed coat, a maternal tissue, so delaying germination favours the inclusive fitness of mothers by reducing the potential for competition among siblings. Seed weight and time to first germination varied significantly amongP. abramsii plants and mean seed weight increased linearly with plant biomass. Seed weight and seed number are independently regulated by plant size. Overall, seed weight varied 10-fold and variability in seed weight within mothers was not explained by plant biomass, seed yield or mean seed weight. GerminableP. abramsii seeds were significantly heavier than dormant seeds, and germinable seeds heavier than 0.20 mg germinated more rapidly than those smaller than 0.20 mg.


Clinical utility of doppler ultrasonography in evaluation of early therapeutic efficacy after transcatheter arterial embolization in patients with hepatocellular carcinoma.
This study was undertaken to determine the value of Doppler ultrasonography in the early evaluation of therapeutic efficacy of hepatocellular carcinoma after transcatheter arterial embolization (TAE). Fifty-two nodules in which tumor vascularity had been detected by Doppler ultrasonography before TAE were examined in 41 patients. Doppler signals were evaluated 1 week after TAE, and the results were compared with tumor vascularity as determined by dynamic magnetic resonance imaging (dynamic MRI), which was used as the gold standard. The sonographic signal disappeared in 41 (79%) of the 52 nodules and remained in 11 (21%). All nodules in which intratumor vascularity had been detected showed positive stain to dynamic MRI. Four of 41 nodules in which the sonographic signal disappeard showed positive stain on dynamic MRI. The Sensitivity of Doppler ultrasonography was 73%; specificity, 100%; and accuracy, 92%. Flow signal in deeply (≥5 cm) located small (<3 cm) nodules tended to be more difficult to detect. We conclude that Doppler ultrasonography warrants use after TAE in the early evaluation as a specific and noninvasive imaging technique.


Dentritic range of the neurons of the intermediate gray at the levels of the first and second lumbar segments of the spinal cord in the cat. 4. The range of dendrites of the lateral horn neurons.
The topography of dendrites of the lateral horn neurons at the level of L1--L2 have been investigated in young and mature cats using Golgi impregnation method. It has been stated that the dendrites of investigated neurons reach the lamina III (dorsally), the lateral funiculi (laterally), and the lateral and central parts of the intermediate gray (medially). They penetrate the thoracic nucleus as well. In their ventral course they were found within the laminae VIII and IX. Afferent connections of the neurons are also discussed.


Exploiting PdII and TiIII chemistry to obtain gamma-dioxygenated terpenoids: synthesis of rostratone and novel approaches to aphidicolin and pyripyropene A.
In nature there are several terpenoids with a characteristic gamma-dioxygenated system on the A ring, and many of them show interesting pharmacological properties. We have developed a novel strategy for the synthesis of these terpenoids involving three stages: (a) the selective epoxidation of commercial polyenes, (b) titanium(III)-catalyzed cyclization of the epoxypolyprenes thus obtained, and (c) Pd-mediated remote functionalization of the equatorial methyl group attached at C-4 on ring A of the cyclic terpenoid thus formed. This strategy has proved to be useful for the synthesis of the natural labdane rostratone (1) and related terpenoids, as well as for advanced synthetic approaches toward the pharmacologically active products aphidicolin (2) and pyripyropene A (3).


Different multi-year mean temperature in mid-summer of South China under different 1.5 °C warming scenarios.
The Paris Agreement proposed a goal of "pursuing efforts to limit the temperature increase to 1.5 °C above pre-industrial levels". The Community Earth System Model, version 1, with the Community Atmosphere Model, version 5 (CESM1-CAM5), designed a set of experiments that fulfilled the 1.5 °C warming goal. By analyzing the outputs, this study aims to present projections associated with warming in South China (SC). Interestingly, if the global mean temperature (GMT) overshoots to 1.7 °C above the pre-industrial levels in 2050 and back to 1.5 °C by 2100, additional warming in the SC mid-summer will occur when approaching 2100 compared to that in the scenario under which the GMT stabilizes at an increase of 1.5 °C after the mid-2040 s. In the final 1 to 3 decades of 21st century in most parts of SC, the multi-year mean warming differences, as well as the difference of extreme hot days, between the two scenarios are significant among the ensembles in mid-summer. Under the scenario in which the GMT overshoots an increase of 1.5 °C, the decrease of mid-level clouds leads to increased downwards solar radiation in the SC and warms the surface, resulting in increases in both outgoing longwave radiation and latent heat flux into the atmosphere and maintenance of the surface balance of the heat budget.


Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?
Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis. Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%). Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708). Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy. Diagnostic test, level V.


Enzyme activities of lactic acid bacteria from a pearl millet fermented gruel (ben-saalga) of functional interest in nutrition.
Lactic acid bacteria responsible for the fermentation of a pearl-millet based fermented gruel, ben-saalga, were investigated for enzyme activity in relation with the nutritional characteristics of gruels used as complementary foods for young children. Thirty pre-selected LAB from a set of 155 isolates were characterized principally for their ability to produce amylase, phytase and alpha-galactosidase. Two Lactobacillus plantarum strains (4.4 and 6.1) and three Lactobacillus fermentum strains (11.11.2, 3.7, 7.4) able to produce one or more of these enzymes were selected. Only weak amylase activity was found in the two Lactobacillus plantarum strains. alpha-amylase activity was associated with cells and was lower than 0.05 Ceralpha Units/ml. Phytase activity was detected in all five strains and was linked to the cell. The highest phytase activity was found in Lb. plantarum 4.4 and 6.1 (348.7 +/- 17.4U/ml and 276.3 +/- 51.4U/ml, respectively) and Lb. fermentum 7.4. (276.3 +/- 13.2U/ml). All strains displayed a cell-linked alpha-galactosidase activity. In a medium containing 2% glucose, the highest cellular activity was found in Lb. fermentum 3.7 (1441.1 +/- 133.7U/ml) and Lb. plantarum 4.4 (1223.1 +/- 148.3U/ml) after 6h of fermentation in the presence of stachyose, and in Lb. plantarum 4.4 (763.3 +/- 23.5U/ml) and Lb. fermentum 7.4 (346.7 +/- 14.8U/ml) after 24h of fermentation with raffinose. These results are consistent with previous observations showing that phytates and alpha-galactooligosaccharides decreased during the natural lactic acid fermentation of pearl millet slurries, and that partial starch hydrolysis can be performed by endogenous microflora provided a pre-gelatinisation step is included in the process.


Environmental risk assessment near a typical spent lead-acid battery recycling factory in China.
In recent years, environmental pollution and public health incidents caused by the recycling of spent lead-acid batteries (LABs) has becoming more frequent, posing potential risk to both the ecological environment and human health. Accurately assessing the environmental risk associated with the recycling of spent LABs is a prerequisite for achieving pollution control. In this study, a spent LABs recycling factory in Chongqing was investigated through on-site investigation, sample analysis. Exposure assessment and health risk assessment were also conducted. The results showed that: firstly, Pb and As concentrations exceeding the standard limit values were found in the environmental air and vegetables near the spent LABs recycling factory. Secondly, exposure assessment results showed that total average daily exposure to hazardous substances for children (3.46 × 10-2 mg/kg) is higher than for adults (4.80 × 10-2 mg/kg). The main exposure pathways for Pb, Cr, Ni, Cu, Zn, and Hg are ingestion of vegetables, while those for Cd, As, and Sb are through inhalation. Thirdly, health risk assessment results indicate that environmental exposure poses unacceptable non-carcinogenic and carcinogenic risk to both adults and children near the spent LABs recycling factory, with children facing higher risk than adults. Pb and As are the main contributors to non-carcinogenic risk, and Ni and As are the main contributors to unacceptable carcinogenic risk. In particular, As, has a greater contribution to total carcinogenic risk index through inhalation than vegetable ingestion. Overall, vegetable ingestion and inhalation are the main exposure pathways for non-carcinogenic and carcinogenic risk. Consequently, future risk assessment should focus on the impact of hazardous substances on children, as well as the health risk associated with ingestion of vegetables and inhalation. Our findings will provide basic information for proposing measures of environmental risk prevention during the recycling of spent LABs, for example, controlling of As in exhaust gas emissions.


Studies on the accumulation and transformation of arsenic in freshwater organisms II. Accumulation and transformation of arsenic compounds by Tilapia mossambica.
Bioaccumulation and biotransformation of arsenic (As) compounds in freshwater Tilapia mossambica was investigated. The direct accumulation of As by T mossambica was proportional to the concentration of arsenicals in water. Small amounts of accumulated As were transformed to methylated As, including trimethylarsenic (TMA) species. Accumulation and transformation of As(III) by T. mossambica via freshwater food chain results in the transformation of As(III) to As(V) with little biomethylation of accumulated As. Approximately 90% of accumulated As was depurated to water.


Evaluating the ecological significance of laboratory response data to predict population-level effects for the estruarine amphipod Ampelisca abdita.
Ten-day acute mortality of the benthic amphipod Ampelisca abdita is used in a number of regulatory, research, and monitoring programs to evaluate chemical contamination of marine sediments. Although this endpoint has proven to be valuable for characterizing the relative toxicities of sediments, the significance of acute mortality with respect to population viability has not yet been established. In this study, population modeling along with empirical extrapolation were used to describe a relationship between acute mortality and population-level response of A. abdita. The research involved the performance of a standard 10-d sediment toxicity bioassay and a 70-d full life-cycle chronic population (including reproduction) bioassay exposing A. abdita to sediments spiked with concentrations of the divalent metal cadmium (normalized to acid volatile sulfide) expected to produce a range of biological effects. These data provided age-specific schedules of survival and fecundity that were used to parameterize an age-classified projection matrix model for A. abdita. Measured exposure data and population growth rate estimates, obtained using the demographic information collected during the 70-d assay, were used to develop exposure-response models. These data were also used to develop an empirical relationship between population growth rate (lambda) and acute mortality. This relationship describes how acute data may be used to predict concentrations that produce population-level effects. Model manipulations permit extrapolation of early life-stage mortality (the acute endpoint) to changes in population growth rate. These relationships were used to evaluate a range of ecologically acceptable acute mortality for A. abdita.


Effects of glucose-insulin-potassium infusion on glycogen levels in cardiac and skeletal muscles in rats.
The effects of loading with glucose-insulin-potassium on the glycogen contents of the heart and peripheral musculature were studied in rats. One group of animals was given intravenous infusion of high concentrations of glucose containing insulin and potassium for 3 days. A control group received the same volume of saline. The hearts and rectus femoris muscles were then analysed for levels of glycogen. It was found that loading with glucose-insulin-potassium induced a decrease in cardiac stores of glycogen while there were no changes in glycogen stores of peripheral musculature as compared to the control animals.


Gynecologic Malignancies.
Gynecologic malignancies are among the most prevalent cancers affecting women worldwide, but they are heterogeneous diseases with varying risk factors, management paradigms, and outcomes. Gynecologic cancers mediated by human papillomavirus (HPV) are preventable and curable with early detection and treatment. Dramatic reductions in cervical cancer incidence and mortality have been achieved through cancer screening and HPV vaccination. Radiotherapy plays a central role in the management of gynecologic malignancies. For some cancers, radiotherapy alone can be curative. More often, radiotherapy is used in conjunction with surgery and systemic therapy to improve locoregional control and extend overall survival. This chapter reviews recent advances in radiotherapeutic management of gynecologic malignancies.


The effects of repetitive proprioceptive stimulation on corticomotor representation in intact and hemiplegic individuals.
To determine the effects of a passive wrist movement intervention on cortical representation of forearm musculature. Transcranial magnetic stimulation was used to map cortical representation of a forearm flexor muscle in healthy individuals and in individuals following stroke before and immediately after a 30 min session of passive wrist movement. In the healthy individuals, no changes in map area or map centre of gravity were noted after the intervention; however, map volume increased significantly across all subjects. In the stroke patient group there were no significant changes in any parameters following the intervention. It is speculated that the enlargement in map volume following the passive movement intervention arose through a heightened synaptic efficacy of the corticospinal pathway in response to the increase in afferent information. Short-term proprioceptive stimulation can induce alterations in corticomotor excitability in the target musculature. These findings provide a potential neural substrate to account for alterations in motor and sensory function in stroke patients in response to long-term passive movement interventions.


Transoral Robotic Surgery and De-escalation of Cancer Treatment.
This article outlines the ways that transoral robotic surgery and transoral laser microsurgery relate to treatment de-escalation in the treatment of head and neck cancer. Treatment de-escalation has particular importance in context of human papillomavirus-related oropharynx squamous cell carcinoma, which responds well to therapy but leaves many survivors with decades of treatment-related sequelae. We compare these less invasive transoral approaches with previously used open approaches to the oropharynx. We discuss the topic of treatment de-escalation in human papillomavirus-related disease and outline completed and ongoing clinical trials investigating the choice of primary treatment modality and de-escalation of adjuvant therapy.


CReg-KD: Model refinement via confidence regularized knowledge distillation for brain imaging.
One of the core challenges of deep learning in medical image analysis is data insufficiency, especially for 3D brain imaging, which may lead to model over-fitting and poor generalization. Regularization strategies such as knowledge distillation are powerful tools to mitigate the issue by penalizing predictive distributions and introducing additional knowledge to reinforce the training process. In this paper, we revisit knowledge distillation as a regularization paradigm by penalizing attentive output distributions and intermediate representations. In particular, we propose a Confidence Regularized Knowledge Distillation (CReg-KD) framework, which adaptively transfers knowledge for distillation in light of knowledge confidence. Two strategies are advocated to regularize the global and local dependencies between teacher and student knowledge. In detail, a gated distillation mechanism is proposed to soften the transferred knowledge globally by utilizing the teacher loss as a confidence score. Moreover, the intermediate representations are attentively and locally refined with key semantic context to mimic meaningful features. To demonstrate the superiority of our proposed framework, we evaluated the framework on two brain imaging analysis tasks (i.e. Alzheimer's Disease classification and brain age estimation based on T1-weighted MRI) on the Alzheimer's Disease Neuroimaging Initiative dataset including 902 subjects and a cohort of 3655 subjects from 4 public datasets. Extensive experimental results show that CReg-KD achieves consistent improvements over the baseline teacher model and outperforms other state-of-the-art knowledge distillation approaches, manifesting that CReg-KD as a powerful medical image analysis tool in terms of both promising prediction performance and generalizability.


Gamma interferon-induced specific binding of tetanus toxin on the GG2EE macrophage cell line.
We have recently demonstrated that tetanus toxin (TT) selectively inhibited gamma interferon-(IFN-gamma)-induced, but not basal, lysozyme activity in the GG2EE macrophage cell line. By an indirect immunofluorescence technique, we show that tetanus toxin, as well as the BIIb tetanus toxin-derived fragment, selectively binds to IFN-gamma-treated cells but fails to bind to control cells. Moreover, BIIb fragment and TT share the same binding sites, as demonstrated by competition/displacement experiments. These data indicate that IFN-gamma pretreatment results in the acquisition of tetanus toxin binding sites on GG2EE cells by a mechanism(s) yet to be identified.


Asterixis as a side effect of carbamazepine therapy.
A patient developed asterixis 13 weeks after starting a therapy with carbamazepine. Serum concentration of carbamazepine was within the therapeutic levels. Further factors which might have provoked asterixis were an impairment of pulmonary function and the combination with a neuroleptic and lithium. Since the latter risk factors had already been present for a long time, it may be assumed that the addition of carbamazepine triggered the development of asterixis.


Granulocytic sarcoma (chloroma) presenting as a lateral neck mass: initial manifestation of leukemia: a case report.
We present a rare case of granulocytic sarcoma (chloroma) in the lateral neck as an initial manifestation of acute leukemia in a 37-year-old man. The lesion appeared as a solid mass with homogenous contrast enhancement on CT. Recognition of this rare entity is important, because early, aggressive induction chemotherapy can improve prognosis.


Duck gut viral metagenome analysis captures snapshot of viral diversity.
Ducks (Anas platyrhynchos) an economically important waterfowl for meat, eggs and feathers; is also a natural reservoir for influenza A viruses. The emergence of novel viruses is attributed to the status of co-existence of multiple types and subtypes of viruses in the reservoir hosts. For effective prediction of future viral epidemic or pandemic an in-depth understanding of the virome status in the key reservoir species is highly essential. To obtain an unbiased measure of viral diversity in the enteric tract of ducks by viral metagenomic approach, we deep sequenced the viral nucleic acid extracted from cloacal swabs collected from the flock of 23 ducks which shared the water bodies with wild migratory birds. In total 7,455,180 reads with average length of 146 bases were generated of which 7,354,300 reads were de novo assembled into 24,945 contigs with an average length of 220 bases and the remaining 100,880 reads were singletons. The duck virome were identified by sequence similarity comparisons of contigs and singletons (BLASTx E score, <10(-3)) against viral reference database. Numerous duck virome sequences were homologous to the animal virus of the Papillomaviridae family; and phages of the Caudovirales, Inoviridae, Tectiviridae, Microviridae families and unclassified phages. Further, several duck virome sequences had homologous with the insect viruses of the Poxviridae, Alphatetraviridae, Baculoviridae, Densovirinae, Iflaviridae and Dicistroviridae families; and plant viruses of the Secoviridae, Virgaviridae, Tombusviridae and Partitiviridae families, which reflects the diet and habitation of ducks. This study increases our understanding of the viral diversity and expands the knowledge about the spectrum of viruses harboured in the enteric tract of ducks.


Familial motor neuron disease with Lewy body-like inclusions in the substantia nigra, the subthalamic nucleus, and the globus pallidus.
In a familial case of motor neuron disease (MND), 2 unusual features were noted in the necropsy. The first was a pallidoluysonigral degeneration, observed in only 4 other cases of MND and which was here asymptomatic. The second was the presence in degenerated spinal cord anterior horns and in degenerated basal ganglia of neuronal Lewy body-like inclusions stained by antibodies against ubiquitin.