Autonomic response to approachability characteristics, approach behavior, and social functioning in Williams syndrome.
Williams syndrome (WS) is a neurogenetic disorder that is saliently characterized by a unique social phenotype, most notably associated with a dramatically increased affinity and approachability toward unfamiliar people. Despite a recent proliferation of studies into the social profile of WS, the underpinnings of the pro-social predisposition are poorly understood. To this end, the present study was aimed at elucidating approach behavior of individuals with WS contrasted with typical development (TD) by employing a multidimensional design combining measures of autonomic arousal, social functioning, and two levels of approach evaluations. Given previous evidence suggesting that approach behaviors of individuals with WS are driven by a desire for social closeness, approachability tendencies were probed across two levels of social interaction: talking versus befriending. The main results indicated that while overall level of approachability did not differ between groups, an important qualitative between-group difference emerged across the two social interaction contexts: whereas individuals with WS demonstrated a similar willingness to approach strangers across both experimental conditions, TD individuals were significantly more willing to talk to than to befriend strangers. In WS, high approachability to positive faces across both social interaction levels was further associated with more normal social functioning. A novel finding linked autonomic responses with willingness to befriend negative faces in the WS group: elevated autonomic responsivity was associated with increased affiliation to negative face stimuli, which may represent an autonomic correlate of approach behavior in WS. Implications for underlying organization of the social brain are discussed.


Prognostic factors of rectal cancer patients with lateral pelvic lymph node metastasis.
We examined the clinicopathological characteristics of rectal cancer patients with lateral pelvic lymph node (LPLN) metastasis in order to clarify their associated prognostic factors. A total of 91 rectal cancer patients with LPLN metastasis who underwent curative resection at the National Cancer Center Hospital between 1985 and 2004 were reviewed. The five-year overall survival rate and disease-free survival rate of the studied patient were 39% and 27%, respectively. Univariate analysis showed that tumor differentiation, lymphatic invasion, venous invasion, mesenteric lymph node status and LPLN status were significant prognostic factors. Multivariate analysis showed that tumor differentiation, mesenteric lymph node status and LPLN status were significant prognostic factors. Among 15 patients with LPLN metastasis and without mesenteric lymph node metastasis, 11 patients (73.3%) with one or two LPLN metastases survived more than five years. Among 12 patients with four or more LPLN metastases, two(16.7%) survived more than five years. Tumor differentiation, mesenteric lymph node status and LPLN status are significant prognostic factors of patients with LPLN metastasis. Because some patients with LPLN metastasis survive for a long period, LPLN dissection should be considered for them.


Utility of caffeine analysis for forensic hair discrimination.
Utility of caffeine analysis for the purpose of forensic hair discrimination was evaluated. Methanol extracts of each 5-cm strand of scalp hair, after its incubation at 37 degrees C for 15 h, was analyzed by gas chromatography-mass spectrometry (GC-MS). For quantitative analysis of caffeine, caffeine-d3 was added as internal standard to the methanol extract. Hair specimens were obtained from three victims and from twenty-two volunteers. The results showed that caffeine levels in hair varied according to each individual; caffeine was detected up to a maximum level of 4.19 ng/5-cm hair. The concentrations of caffeine in hair obtained from four different regions of the scalp in twenty-two volunteers showed a coefficient of variation not greater than 24.7% for each individual. Based on our data, it was concluded that caffeine levels give relatively high reliability for discriminating a victim's hair from others at a criminal or accidental scene, although it should be used in combination with morphological examination and ABO blood group determination.


Some psychological relations between action and language structure.
This study investigated the relationship between complex grammatical structures and complex action sequences. A developmental progression of strategies for combining seriated cups identified in an earlier study (Greenfield et al., 1972) was used to demonstrate some psychological consequences of formal parallels between language and action. The role of grammatical complexity and situational structure in language-action relations was explored. The results have implications for understanding the organization and development of complex action, its control by verbal commands, and the basic processes of speech comprehension.


Early-stage diffuse large B cell lymphoma of the head and neck: clinico-biological characterization and 18 year follow-up of 488 patients (IELSG 23 study).
It is known that extranodal head and neck diffuse large B cell lymphomas (eHN-DLBCL) can affect various anatomical structures what is not well-known, however, is whether they differ in terms of clinical presentation and outcome. Clinical data of the multi-institutional series, the largest of its kind as yet, has been analysed with the aim of answering these open questions and providing long-term follow-up information. Data from 488 patients affected by stage I/II eHN-DLBCL was collected: 300 of the Waldeyer's Ring (WR), 38 of the parotid and salivary glands (PSG), 48 of the thyroid gland (TG), 53 of the nasal cavity and paranasal sinuses (NPS), 24 of the palate and oral cavity (POC) and 25 with more than one involved site. Different eHN-DLBCL arising have distinct characteristics at presentation. The intermediate high risk-modified IPI was 67 % in TG, 44 % in WR, 38 % in PSG and POC and 20 % in MS. The worst 5-year survival rate had TG-DLBCL (61 %) due to the 61 % of patients with a mIPI >1. The addition of radiotherapy (cRT) to remitters did not translate into a survival advantage (5-year disease-free survival of 67 % in the cRT group vs. 70 % in the other). Three of four central nervous system recurrences occurred in NPS-DLBCL. Survival of HN-DLBCL was inferior to nodal DLBCL. This study showed that eHN-DLBCL remitters have an inferior survival when compared to nodal DLBCL, and that the addition of cRT does not provide a survival advantage. Since the standard of care nowadays is chemo-immunotherapy, survival of these patients might have been improved.


Early intravitreal bevacizumab for non-ischaemic central retinal vein occlusion.
To evaluate the effect of early intravitreal bevacizumab injections for the treatment of macular oedema caused by non-ischaemic central retinal vein occlusion (CRVO). The study included 25 patients (25 eyes) with macular oedema caused by non-ischaemic central retinal vein occlusion, who received three intravitreal injections of 1.5 mg bevacizumab with an interval of 6 weeks between the injections. Mean duration of central retinal vein occlusion prior to the first injection was 4.2 +/- 3.6 days. All patients were re-examined 1, 3 and 6 months after the first injection. The main outcome parameters were visual acuity and macular thickness, as measured by optical coherence tomography. Mean visual acuity improved significantly from 0.97 +/- 0.40 logMAR at baseline to 0.70 +/- 0.42 logMAR (P = 0.007) at 1 month, 0.69 +/- 0.46 (P = 0.006) 3 months and 0.69 +/- 0.52 (P = 0.015) 6 months after the first injection. Mean central retinal thickness decreased significantly from 530 +/- 152 microm at baseline to 347 +/- 127 microm (P < 0.001) at 1 month, 370 +/- 165 microm (P < 0.001) 3 months and 346 +/- 129 microm (P < 0.001) 6 months (P < 0.001) after the first injection. The increase in visual acuity correlated significantly (P < 0.01) with the decrease in macular thickness. Mean intraocular pressure was 14.2 +/- 3.2 mmHg at baseline and did not differ significantly from the measurement obtained at 1 month (P = 0.59), 3 months (P = 0.88) and 6 months after the first injection (P = 0.65). Intravitreal bevacizumab injections given shortly after onset of non-ischaemic central retinal vein occlusion may result in a significant increase in vision and a corresponding decrease in macular oedema.


Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome.
Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome. Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis. Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBFConclusion:In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted.


Unilateral proptosis in a patient with thyroid eye disease: A case report.
Unilateral proptosis is an abnormality in which one eye sticks out forward more than the other. Bulging of the eye is commonly seen in Graves' ophthalmopathy, but it's mostly bilateral. Thyroid eye disease presents as the most common extrathyroidal manifestation of Graves' disease, and rarely leads to unilateral proptosis. A 25-year-old female with a history of weight loss, menstrual irregularities, and palpitations presented with progressive right eye bulging, which was further confirmed by magnetic resonance imaging and biochemical investigations. Magnetic resonance imaging of the orbit revealed unilateral extraocular muscle enlargement and enhancement with sparing of the tendons. Timely therapy is crucial for reversing the ocular manifestations of thyroid eye disease.


Reconstruction of an idiopathic hemipalatal hypoplasia: report of a case.
Idiopathic hemipalatal hypoplasia is rare and leads to speech problems and the regurgitation of fluids, and the reconstruction of asymmetrical velopharyngeal incompetence is a challenge to the cleft surgeon. We present a case in a 5-year-old boy, and introduce the one-stage surgical technique that we used to resolve it.


Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension.
Pharmacodynamics and pharmacokinetics of labetalol, a combined alpha- and beta-adrenoceptor antagonist drug, were studied in elderly and young hypertensive patients. After receiving intravenous labetalol, elderly patients had a greater maximal mean decrease in systolic blood pressure (BP) (39 +/- 8 vs 25 +/- 13 mm Hg, p less than 0.02); however, maximal decrease in diastolic BP was similar in elderly (18 +/- 10 mm Hg) and young (17 +/- 6 mm Hg) patients. After receiving oral labetalol, elderly patients had a greater maximal decrease in standing systolic BP (41 +/- 16 vs 16 +/- 14 mm Hg, p less than 0.001) and similar decreases in standing diastolic BP (21 +/- 7 vs 17 +/- 9 mm Hg). Sitting maximal BP decreases after oral labetalol treatment were similar in elderly and young patients (12 +/- 16 vs 17 +/- 7 mm Hg systolic and 24 +/- 6 vs 12 +/- 7 diastolic). The decrease in heart rate was greater in young patients after intravenous labetalol administration. To evaluate labetalol pharmacodynamics, a linear model was used. Slope of labetalol concentration vs systolic BP for elderly vs young patients was 0.928 +/- 1.05 vs 0.326 +/- 0.490 ng/ml X mm Hg-1 (difference not significant). The slope of labetalol concentration vs heart rate for elderly vs young patients was 0.176 +/- 0.063 vs 0.406 +/- 0.303 ng/ml X beats/min-1 (p less than 0.05), with 2 elderly patients showing no decrease in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Arithmetic statistics of Prym surfaces.
We consider a family of abelian surfaces over Q arising as Prym varieties of double covers of genus-1 curves by genus-3 curves. These abelian surfaces carry a polarization of type (1, 2) and we show that the average size of the Selmer group of this polarization equals 3. Moreover we show that the average size of the 2-Selmer group of the abelian surfaces in the same family is bounded above by 5. This implies an upper bound on the average rank of these Prym varieties, and gives evidence for the heuristics of Poonen and Rains for a family of abelian varieties which are not principally polarized. The proof is a combination of an analysis of the Lie algebra embedding F4⊂E6, invariant theory, a classical geometric construction due to Pantazis, a study of Néron component groups of Prym surfaces and Bhargava's orbit-counting techniques.


Location of the ovaries in children and efficacy of gonadal shielding in hip and pelvis radiography.
Patients with hip disorders undergo multiple radiographic examinations, so gonadal radiation risk should be minimized. Inaccurate shield placement, including obscuring landmarks, has been widely reported, and some studies reported that covering the true pelvis was inappropriate to shield young girls' ovaries. However, no reports on ovaries in Asian patients identified on magnetic resonance imaging exist. We aimed to identify the location of the ovaries in Japanese children and assess the efficacy of gonadal shielding. Female patients aged ≤16 years who underwent magnetic resonance imaging for hip disorders that displayed at least one ovary were included. Sixty ovaries from 31 patients were classified into two age groups: <2 years and >2 years, and the ovaries' position was classified according to the following four zones on the anteroposterior pelvic radiograph: zone 1 (true pelvis) - area surrounded by the line of the anterior superior iliac spines, inner side walls of the ilium, and symphysis pubis; zone 2 - areas lateral to zone 1; zone 3 - sacral area superior to zone 1; and zone 4 - areas lateral to zone 3. The ovaries' position was analyzed according to age group. Thirty-one ovaries in 16 patients were <2 years, and 29 ovaries in 15 patients were >2 years. Thirteen ovaries in the true pelvis, 18 ovaries in the false pelvis were <2 years, and 27 in the true pelvis and 2 in the false pelvis were in >2 years. In girls aged <2 years, most ovaries in the false pelvis were located in zone 3. Girls aged >2 years mostly have their ovaries in the true pelvis, and ovaries in infants tend to be located superior to the true pelvis. Covering the true pelvis is plausible for shielding ovaries. Shields should be placed slightly more cranially than the true pelvis for infants.


New modes of mechanical ventilation.
The new modes and techniques of ventilation provide much needed alternative ventilatory support for the critically ill patient. Reduction of airway pressure, improved oxygenation, recruitment of alveoli, and redistribution of ventilation are the major advantages of these new modes. Continued research and clinical application will help develop a mechanical ventilation system that optimizes the patient respiratory status with minimal adverse effects.


Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2.
Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2-20 μg/implant) on the CaP-based bone substitute material and implanted for 4 and 12 weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies.


Colour vision screening in children: an evaluation of three pseudoisochromatic tests.
We examined 513 children (258 boys and 255 girls), between 3 and 11 years of age, with three pseudoisochromatic tests which involve different visual tasks. These were a selection of numeral designs from the Ishihara test, the Ishihara test for Unlettered Persons and the Velhagen Pfügertrident test. Eighteen children were found to be colour deficient. The symbol designs of the Unlettered Persons test were found to be the quickest and most effective method for examining children under 7 years of age. After 7 years of age the symbol designs of the Unlettered test and the numeral designs of Ishihara test were equally effective. The preferred numeral designs for screening children with the Ishihara plates are listed. Verbal identification always produced the most accurate results. Drawing over the figures or selecting replicas increased the viewing time and assisted children with normal colour vision to see both figures in transformation designs, especially pathway designs. The Velhagen Pfügertrident test was found to be unreliable for colour vision screening and younger children had difficulty performing the figure matching task.


Synthesis, characterization, and biological studies of chalcone derivatives containing Schiff bases: Synthetic derivatives for the treatment of epilepsy and Alzheimer's disease.
In this study, first, Schiff base-containing chalcone derivatives were synthesized. The human carbonic anhydrase (hCA) isoenzymes I and II were then purified from human erythrocytes using Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. In addition, the inhibitory effects of the newly synthesized compounds on the activities of hCA and acetylcholinesterase (AChE) were investigated in vitro, using the esterase and acetylcholine iodide method. The IC50 values were determined and the Ki values of AChE and hCA activities were calculated from the Lineweaver-Burk graphs determined in this study. The hCA I isoform was inhibited by these chalcone derivatives containing Schiff bases (3a-j and 5a-f) in low nanomolar levels, whose Ki values ranged between 141.88 ± 24.10 and 2,234.47 ± 38.11 nM. Against the physiologically dominant isoform hCA II, the compounds demonstrated Ki values varying from 199.31 ± 40.45 to 602.79 ± 263.22 nM. Also, these compounds effectively inhibited AChE, with Ki values ranging from 20.41 ± 6.04 to 125.94 ± 23.88 nM. According to these results, the newly synthesized molecules were found to be potent inhibitors of these enzymes.


Characterization of copper binding to different molecular weight fractions of dissolved organic matter in surface water.
Dissolved organic matter (DOM) is a kind of substance with complex compositions and wide molecular weight distribution, which can strongly combine with various pollutants. Therefore, the binding characteristics of DOM and heavy metal pollutants can be studied specifically according to the binding characteristics of DOM and pollutants. In this study, DOM in surface water bodies was divided into three levels (MW < 1 kDa, 1 kDa < MW < 5 kDa, MW > 5 kDa) according to different molecular weights (MW). The binding properties were investigated by fluorescence spectrum analysis and complex model. Four components (C1-C4) were identified by PARAFAC. Among them, the contribution rate of protein-like components C1, C2 and C4 to the total fluorescence intensity reached more than 78%, and the log Ka values of low molecular weight components were the highest, which were 3.28, 3.14 and 3.47, respectively, indicating higher binding ability with Cu2+.With the decrease of molecular weight, the log Kb value increases, indicating that the complexation is more stable. The humic component C3 in high molecular weight has stronger binding stability with Cu2+, but the number of binding sites for C3 is 0.36, while that for C2 is 1.51, indicating that its binding sites and binding ability are relatively low. The results showed that the DOM ligand of Cu2+ in surface water showed a certain molecular weight dependence. In addition, different MW DOM lead to different pollution forms. Different properties of DOM ligand combined with Cu2+ were studied in order to control the migration, transformation, bioavailability, morphology and stability of heavy metal pollutants, and to provide theoretical support for the practical application management of surface water pollution control.


Consumption of nematodes by fungivorous mites, Tyrophagus spp. (Acarina: Astigmata: Acaridae).
Free-living nematodes may be attacked and eaten by soil mites which are normally considered fungivores or saprophages. Three species in the genus Tyrophagus, common inhabitants of grassland soils and also common pests in stored products, museums and laboratories, are predators of nematodes. All active stages of the mites will voraciously consume nematodes. When offered nematodes and a choice of other food (baker's yeast and algae), 11% of the Tyrophagus putrescentiae, 23% of the T. zachvatkini, and 56% of the T. similis tested fed on nematodes. Tyrophagus zechvatkini and similis were reared on a diet consisting entirely of nematodes, and developed at rates similar to a fungal diet and produced viable offspring. Agar cultures of Aphelenchus avenae which were inoculated with five mating pairs of Tyrophagus zachvatkini had populations that were one-third less than mite-free controls. Observations indicate that nematodes may be attacked by tyrophagid mites when in a dry, anhydrobiotic state.


Automatic ICD-10 coding: Deep semantic matching based on analogical reasoning.
ICD-10 has been widely used in statistical analysis of mortality rates and medical reimbursement. Automatic ICD-10 coding is desperately needed because manually assigning codes is expensive, time-consuming, and labor-intensive. Diagnoses described in medical records differ significantly from those used in ICD-10 classification, making it impossible for existing automatic coding techniques to perform well enough to support medical billing, resource allocation, and research requirements. Meanwhile, most of the current automatic coding approaches are oriented toward English ICD-10. This method for automatically assigning ICD-10 codes to diagnoses extracted from Chinese discharge records was provided in this paper. First, BERT creates word representations of the two texts. Second, the context representation layer incorporates contextual information into the representation of each time step of the word representations using a bidirectional Long Short-Term Memory. Third, the matching layer compares each contextual embedding of the uncoded diagnosis record against a weighted version of all contextual character embeddings of the manually coded diagnosis record. The matching strategy is element-wise subtraction and element-wise multiplication and then through a neural network layer. Fourth, the matching vectors are combined using a one-layer convolutional neural network. A sigmoid is then used to output matching results. To evaluate the proposed method, 1,003,558 manually coded primary diagnoses were gathered from the homepage of the discharge medical records. The experimental results showed that the proposed method outperformed popular deep semantic matching algorithms, such as DSSM, ConvNet, ESIM, and ABCNN, and demonstrated state-of-the-art results in a single text matching with an accuracy of 0.986, a precision of 0.979, a recall of 0.983, and an F1-score of 0.981. The automatic ICD-10 coding of Chinese diagnoses is successful when using the proposed deep semantic matching approach based on analogical reasoning.


Oxodealkenylative Cleavage of Alkene C(sp3 )-C(sp2 ) Bonds: A Practical Method for Introducing Carbonyls into Chiral Pool Materials.
Reported herein is a one-pot protocol for the oxodealkenylative introduction of carbonyl functionalities into terpenes and terpene-derived compounds. This transformation proceeds by Criegee ozonolysis of an alkene, reductive cleavage of the resulting α-alkoxy hydroperoxide, trapping of the generated alkyl radical with 2,2,6,6-tetramethylpiperidin-1-yl (TEMPO), and subsequent oxidative fragmentation with MMPP. Using readily available starting materials from chiral pool, a variety of carbonyl-containing products have been accessed rapidly in good yields.


Self-reported internalization symptoms and family factors in indigenous Sami and non-Sami adolescents in North Norway.
Through differences in family socialization between indigenous and non-indigenous youth, there may be cultural differences in the impact of family factors on mental health outcome. Using structural equation modelling, this population-based study explored the relationship between symptoms of anxiety and depression and family factors in indigenous Sami and non-Sami boys and girls in North Norway. The findings show that family income was to a lesser degree related to internalization symptoms for Sami youth than non-Sami youth. For all groups except for Sami girls, family conflict and moving was associated with increasing symptoms. Sami boys differed from the other three groups with regard to the relationship between family connectedness and symptom level. These interaction effects were discussed in light of traditional Sami values and gender socialization. The present study has indicated that in the family socialization context, culture may be related to internalization symptoms in youth.


Upregulation of HMGB1 secretion in lungs of pigs infected by highly pathogenic porcine reproductive and respiratory syndrome virus.
Porcine reproductive and respiratory syndrome (PRRS) remains a major driver for substantial economic losses to the swine industry across the world. Pulmonary inflammatory injury is a common manifestation in infected pigs. Previous studies reported that PRRS virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1), a proinflammatory factor, in cultured cells. The objective of this study was to evaluate whether HMGB1 secretion is associated with PRRSV-induced pulmonary inflammatory responses in the early stage of infection in vivo. Three-week-old piglets were inoculated with either HuN4, a highly pathogenic PRRSV (HP-PRRSV) strain, or CH1R, an avirulent PRRSV vaccine strain. Necropsy was performed at 7 days post-infection. The results showed that HuN4 significantly induced the secretion of HMGB1 and inflammatory cytokines (IL-1β, IL-6) into the bronchoalveolar lavage fluid (BALF). HuN4 infection induced severe interstitial pneumonia in the pigs. In contrast, pigs infected by CH1R had mild lung inflammation with minimal HMGB1 secretion. In addition, high viral load of HuN4 was detected in both pulmonary alveolar macrophages (PAMs) and lung tissue, whereas viral RNA of CH1R was confined to PAMs. In consistent with the pneumonia development, HuN4 induced inflammatory cytokines in both PAMs and lung tissue, while their expression in CH1R-infected pigs confined only to PAMs. These results indicate that the HuN4-induced HMGB1 secretion into BALF may enhance the pulmonary inflammatory response and exacerbate the lung injury. This finding provides insights to the inflammatory response and pathogenesis of the HP-PRRSV infection.


High doses of penicillin decreases [3H]flunitrazepam binding sites in rat neuron primary culture.
Penicillin (PC) neurotoxicity (convulsions and encephalopathy) is considered to be due to GABAergic inhibition. The effects of penicillin G(PCG) on [3H]flunitrazepam (FNZ) binding in rat neuron-enriched primary cultures was examined to assess the role of the benzodiazepine (BDZ) receptor in the neurotoxicity. PCG application for 24 h induced a significant decrease in [3H]FNZ binding activity at 10(-3) M, and a decrease in available receptor number (Bmax) at 10(-2) M, without obvious cell damage. Pre-application of the BDZ receptor antagonist, Ro-15-1788, prevented the PC-induced decrease in [3H]FNZ binding activity. Therefore, PC seems to reduce the number of BDZ receptors through a direct effect on this receptor, which is a part of the major inhibitory system in mammalian brain; the GABAergic macromolecular receptor complex. This decrease in BDZ receptors may play a role in PC-induced neurotoxicity, especially encephalopathy.


Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities.
Intoplicine (RP 60475, NSC 645008) is an antitumor derivative in the 7H-benzo[e]pyrido[4,3-b]indole series which is now being tested in clinical trials. Intoplicine strongly binds DNA (KA = 2 x 10(5) M-1) and thereby increases the length of linear DNA. These properties are consistent with DNA unwinding by intoplicine. Intoplicine was found to be a dual topoisomerase I and II inhibitor, with DNA sites of enzyme inhibition being different for these two enzymes. In this study, 22 analogues of intoplicine were evaluated for their effects on topoisomerase I- and II-mediated DNA cleavage reactions by using enzymes purified from calf thymus. Site-specific DNA cleavage mediated by topoisomerase I was observed with 7H-benzo[e]pyrido[4,3-b]indole derivatives but not with 11H-benzo[g]-pyrido[4,3-b]indole derivatives. Site-specific DNA cleavage mediated by topoisomerase II occurred with derivatives having hydroxyl groups at the 3-position on the 7H-benzo[e]pyrido[4,3-b]indole ring or at the 4-position on the 11H-benzo[g]pyrido[4,3-b]indole ring. Study of the relationships between the in vivo antitumor activity on P388 leukemia and the topoisomerase I- and/or II-mediated DNA cleavage activity revealed that the most highly active antitumor compounds possessed both topoisomerase I-and II-inhibitory properties. Compounds selectively inhibiting either topoisomerase I or II were less active. These results suggest that dual topoisomerase I and II inhibition is critical for the antitumor activity of this new series of antitumor compounds.


Respiratory infection due to direct contact with rabbit-skin powder contaminated by vaccinia virus.
Vaccinia virus infection was diagnosed in five male workers directly exposed to rabbit-skin powder contaminated by vaccinia virus via skin contact and inhalation. Four of the workers had been vaccinated against smallpox. Their clinical symptoms were severe, especially in the lungs; however, all symptoms improved after treatment.


miR-146a regulates insulin sensitivity via NPR3.
The pathogenesis of obesity-related metabolic diseases has been linked to the inflammation of white adipose tissue (WAT), but the molecular interconnections are still not fully understood. MiR-146a controls inflammatory processes by suppressing pro-inflammatory signaling pathways. The aim of this study was to characterize the role of miR-146a in obesity and insulin resistance. MiR-146a-/- mice were subjected to a high-fat diet followed by metabolic tests and WAT transcriptomics. Gain- and loss-of-function studies were performed using human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Compared to controls, miR-146a-/- mice gained significantly more body weight on a high-fat diet with increased fat mass and adipocyte hypertrophy. This was accompanied by exacerbated liver steatosis, insulin resistance, and glucose intolerance. Likewise, adipocytes transfected with an inhibitor of miR-146a displayed a decrease in insulin-stimulated glucose uptake, while transfecting miR-146a mimics caused the opposite effect. Natriuretic peptide receptor 3 (NPR3) was identified as a direct target gene of miR-146a in adipocytes and CRISPR/Cas9-mediated knockout of NPR3 increased insulin-stimulated glucose uptake and enhanced de novo lipogenesis. In summary, miR-146a regulates systemic and adipocyte insulin sensitivity via downregulation of NPR3.


Identification and reliability of microbial aerobic respiration and denitrification kinetics using a single-well push-pull field test.
Methods to derive reaction rates of microbial processes are important since these processes are determining many chemical reactions influencing groundwater quality. Thereby, it is not only important to derive the parameters, but also to have a firm idea about the reliability with which these are determined. Analysis of residuals, sensitivity analyses and analysis of joint confidence intervals provide an interesting tool for this purpose. The method is illustrated in this paper using a push-pull test designed to derive aerobic respiration and denitrification. Therefore, a test solution containing dissolved oxygen and nitrate as reactive tracer and bromide as non-reactive tracer was injected in organic matter rich sediment. Afterwards, this test solution was extracted and water quality was monitored. ReacTrans, a finite-difference, axial-symmetric groundwater flow and solute transport model was developed to simulate the test and derive hydraulic, solute transport and chemical parameters. Aerobic respiration and denitrification were simulated with Michaelis-Menten kinetics. Maximum reaction rates (10.4 and 2.4 mmol/ld for aerobic respiration and denitrification respectively) and Michaelis constants (0.14 and 0.1 mmol/l for aerobic respiration and denitrification respectively) were determined. The reliability with which these parameters are derived is indicated by analysis of residuals, sensitivities and joint confidence intervals. This shows that the Michaelis-Menten parameters can be derived reliable with a push-pull test, whereas the test is insensitive to effective porosity and hydraulic conductivity. Because of the small scale of the test, longitudinal dispersivity was very small and therefore unidentifiable.


Evaluation of segmental spinal cord evoked magnetic fields after sciatic nerve stimulation.
We have previously reported that the measurement of spinal cord evoked magnetic fields (SCEFs) could be a helpful method for evaluating spinal cord function or detecting conduction blocks in the spinal cord. However, there have been no reports about segmental-SCEFs as a complex of axonal and synaptic activities in the spinal cord. The purpose of this study is to record and evaluate segmental-SCEFs. The segmental-SCEFs were measured over the lumbar dural tubes of adult rabbits using our SQUID system following sciatic nerve stimulation; spinal cord evoked potentials (SCEPs) were also measured to compare the results. SCEPs showed conductive sharp waves following gentle waves, suggesting action potentials and synaptic potentials, respectively. The isomagnetic field maps of SCEFs showed a quadrupolar pattern propagating from the caudal to the cranial region within a short latency time, and after the conductive magnetic fields passed, stationary dipolar fields appeared and were sustained at some vertebral levels. The quadrupolar magnetic fields were estimated to be generated from conducting action potentials, and the dipolar fields were thought to be caused by synaptic activities. Through the measurement of segmental-SCEFs, the conductive neural and synaptic activities in the spinal cord can be visualized and distinguished. This is the first report to record and visualize the sequence of events ranging from the axonal activities of peripheral nerves and the spinal tract to the synaptic activities in the spinal cord.


Metal composition of human hepatic and renal metallothionein.
This article is based on data on the levels of metals (Cd, Zn, Cu) and metallothionein (MT) determined radiochemically with 203Hg in renal cortex and liver of 137 autopsy cases. From this number, for 23 cases, the gel filtration of the cytoplasmic fraction of the organs was performed. The molar content of metals in the MT fraction (Sephadex G-50) amounted to 46.9, 50.2, and 2.0% for Cd, Zn, and Cu in renal cortex, respectively, and to 8.3, 83.6, and 9.1% for Cd, Zn, and Cu in the liver, respectively. In parallel with the increase of Cd and MT in renal cortex, increasing saturation was found of the MT fraction by Cd, occurring at the expense of Zn and Cu. Equimolar amounts of Cd and Zn in the MT fraction are found at Cd level of 0.5 micromol Cd/g wet wt of renal cortex. In the liver, analogous dependency (elevation of %Zn, depression of %Cd and %Cu) were observed in relation to Zn and MT levels in this organ. The basic level of Zn (not bound with MT) was estimated at 0.5 micromol/g for both renal cortex and liver. A deficit of non-MT Zn in kidneys is proposed as an alternative mechanism of toxic Cd action.


Reconstruction of three dimensional structures from electron micrographs.
General principles are formulated for the objective reconstruction of a three dimensional object from a set of electron microscope images. These principles are applied to the calculation of a three dimensional density map of the tail of bacteriophage T4.


Molecular characterization of the full-length L and M RNAs of Tomato yellow ring virus, a member of the genus Tospovirus.
Tomato yellow ring virus (TYRV), first isolated from tomato in Iran, was classified as a non-approved species of the genus Tospovirus based on the characterization of its genomic S RNA. In the current study, the complete sequences of the genomic L and M RNAs of TYRV were determined and analyzed. The L RNA has 8,877 nucleotides (nt) and codes in the viral complementary (vc) strand for the putative RNA-dependent RNA polymerase (RdRp) of 2,873 amino acids (aa) (331 kDa). The RdRp of TYRV shares the highest aa sequence identity (88.7 %) with that of Iris yellow spot virus (IYSV), and contains conserved motifs shared with those of the animal-infecting bunyaviruses. The M RNA contains 4,786 nt and codes in ambisense arrangement for the NSm protein of 308 aa (34.5 kDa) in viral sense, and the Gn/Gc glycoprotein precursor (GP) of 1,310 aa (128 kDa) in vc-sense. Phylogenetic analyses indicated that TYRV is closely clustered with IYSV and Polygonum ringspot virus (PolRSV). The NSm and GP of TYRV share the highest aa sequence identity with those of IYSV and PolRSV (89.9 and 80.2-86.5 %, respectively). Moreover, the GPs of TYRV, IYSV, and PolRSV share highly similar characteristics, among which an identical deduced N-terminal protease cleavage site that is distinct from all tospoviral GPs analyzed thus far. Taken together, the elucidation of the complete genome sequence and biological features of TYRV support a close ancestral relationship with IYSV and PolRSV.


A novel strategy for rapid and efficient isolation of human tumor-specific CD4(+) and CD8(+) T-cell clones.
Adoptive therapy with antigen-specific T cells is a promising approach for the treatment of infectious diseases and cancer. However, cloning of antigen-specific T cells by the traditional approach of limiting dilution is a time-consuming, laborious, and inefficient process. Here, we describe a novel flow cytometric strategy for rapid isolation of human tumor antigen-specific T-cell clones by using T-cell receptor (TCR) Vbeta antibodies in combination with carboxyfluorescein succinimidyl ester (CFSE)-based proliferation assay. The CFSE dilution following antigen stimulation identified proliferating antigen-specific T cells, and the TCRVbeta antibodies allowed distinguishing T cells at the clonal level from a heterogeneous T-cell population. This method of TCRVbeta/CFSE dilution was used for the isolation of four different human lymphoma and melanoma-specific CD4(+) and CD8(+) T-cell clones reactive against defined and undefined tumor antigens. Isolated tumor-specific T-cell clones could be expanded to large numbers ex vivo while maintaining phenotype, function, and tumor antigen specificity. The method was simple, efficient, and reproducible, and may have potential application for the development of adoptive immunotherapeutic strategies.


Management of Gastrointestinal Stromal Tumors.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is the most common site of origin. Management of GISTs changed after the introduction of molecularly targeted therapies. Although the only potentially curative treatment of resectable primary GISTs is surgery, recurrence is common. Patients with primary GISTs at intermediate or high risk of recurrence should receive imatinib postoperatively. Imatinib is also first-line therapy for advanced disease. Cytoreductive surgery might be considered in advanced GIST for patients with stable/responding disease or limited focal progression on tyrosine kinase inhibitor therapy. GIST requires multidisciplinary management.


The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat.
Discharges were recorded from spinal dorsal horn neurons in response to noxious skin heating (e.g. 50 degrees C). Repetitive electrical stimulation of the mesencephalic periaqueductal gray (PAG) inhibited these nociceptive discharges. In each of 9 experiments systemic administration of naloxone (1-3 mg/kg) did not affect this descending inhibition, arguing against involvement of endogenous opiates.


Assessment of critical renal ischemia with real-time infrared imaging.
Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfusion of brain tumors and kidneys during human surgery. Intraoperative IR imaging has the potential for more objective real-time detection and quantitative assessment of organ viability including early ischemia. We hypothesize, by detecting variations of the IR signal, we can assess the degree to which renal surface temperature reflects underlying renal ischemia. To address this hypothesis, IR imaging-derived temperature fluctuations were evaluated during laparotomy in a porcine model (n = 15). These temperature profiles then underwent spectral (frequency) analysis to assess their relationship to well-described oscillations of the microcirculation. An IR camera was positioned 30-60 cm above the exposed kidneys. Images (3-5 mum wavelength) were collected (1.0/s) at baseline, during warm renal ischemia, and during reperfusion. Dominant frequency (DF) of the tissue temperature fluctuations were determined by a Fourier transformation (spectral) analysis. IR images immediately showed which segments of the kidney were ischemic. DF at approximately 0.008 Hz that corresponds to blood flow oscillations was observed in thermal profiles. The oscillations were diminished or disappeared after 25 min of warm ischemia and were recovered with reperfusion in a time-dependent fashion. Oscillations were attenuated substantially in ischemic segments, but not in perfused segments of the kidney. The described oscillations can be measured noninvasively using IR imaging in the operating room, as represented by the DF, and may be an early marker of critical renal ischemia.


11,17-dideoxyagelorin A and B, new bromotyrosine derivatives and analogs from the marine sponge Suberea aff. praetensa.
A collection of the marine sponge Suberea aff. praetensa from the Gulf of Thailand furnished the bromotyrosine derivatives fistularin-3, agelorins A and B and the new desoxyagelorins A and B.


State of the art in the treatment of gastric cancer: from the 71st Japanese Gastric Cancer Congress.
The recent literatures has few reports of the state of the art and latest results in the treatment of gastric cancer, although such information is necessary for conducting new clinical trials and for obtaining informed consent from patients. In the panel discussions at the 71st Gastric Cancer Congress of Japan (held in Tokyo, June 1999), 18 representative institutions and hospitals in Japan reported their latest results for the surgical treatment of gastric cancer, indicating the state of the art in the treatment of gastric cancer. Here we report a summary of these sessions.


Inequality and visibility of wealth in experimental social networks.
Humans prefer relatively equal distributions of resources, yet societies have varying degrees of economic inequality. To investigate some of the possible determinants and consequences of inequality, here we perform experiments involving a networked public goods game in which subjects interact and gain or lose wealth. Subjects (n = 1,462) were randomly assigned to have higher or lower initial endowments, and were embedded within social networks with three levels of economic inequality (Gini coefficient = 0.0, 0.2, and 0.4). In addition, we manipulated the visibility of the wealth of network neighbours. We show that wealth visibility facilitates the downstream consequences of initial inequality-in initially more unequal situations, wealth visibility leads to greater inequality than when wealth is invisible. This result reflects a heterogeneous response to visibility in richer versus poorer subjects. We also find that making wealth visible has adverse welfare consequences, yielding lower levels of overall cooperation, inter-connectedness, and wealth. High initial levels of economic inequality alone, however, have relatively few deleterious welfare effects.


[Anhydrous theophylline in micropellets with prolonged action in asthmatic children].
The present study was realized to evaluate the effectiveness, security and tolerability of slow release micro pellets theophylline, in a group of 168 asthmatic children, between 2 and 15 years old. The improvement of the symptoms was obtained, since the treatment began. The final evaluation was considered excellent and good in 86.90% of the cases, and the tolerability, excellent and good in 94.64% of the patients. In conclusion the slow-release micro pellets theophylline is a very effective and secure drug, with a very good tolerability for the treatment of the asthmatics in pediatric age.


Detection of antibody to Theileria parva schizonts and cell surface membrane antigens of infected lymphoblastoid cells by immunoperoxidase techniques.
Peroxidase-labeled antibody procedures were described for detecting bovine antibodies reactive with intracellular Theileria parva schizonts and cell surface membrane antigens of infected lymphoblastoid cells. Indirect tests were performed where the reacting bovine antibodies were localized with affinity purified rabbit-anti-bovine IgG coupled to horseradish peroxidase. A 4- to 8-fold increase in sensitivity for detecting bovine antibodies was obtained with unlabeled rabbit-anti-bovine IgG which in turn was detected with peroxidase labeled goat-anti-rabbit IgG. The T. parva infected cells used as antigen were attached to poly-l-lysine treated glass slides and all reaction steps were performed on the slides. The intracellular schizonts and cell surface staining reactions were dependent upon the status of the cells; acetone-fixed cells were required for schizont reactions and viable unfixed cells for cell surface membrane reactions. Sera from cattle stimulated in various ways with T. parva were examined by the techniques. Cattle infected by stabilate inoculation or inoculated with infected autologous lymphoblastoid cells developed relatively high levels of antibody to schizonts, but no detectable antibody to cell surface membrane antigens. This would indicate that parasite antigens do not occur on the surface of infected lymphoblasts. Cattle inoculated with infected allogeneic lymphoblasts developed low-levels of antibody to schizonts and readily demonstrable antibody to cell surface antigens. The immunoperoxidase procedures have certain advantages over immunofluorescence in that light microscopy is used; therefore, the reactions do not fade which permits a more detailed examination and provides a relatively permanent record, the preparations can be counterstained, and the reagents may be used for immunoelectron-microscopy. The procedures could provide suitable alternatives to immunofluorescence methods for East Coast fever investigations and other systems having intracellular and/or cell surface membrane antigens.


Effect of buflomedil chlorhydrate on local oxygen delivery in peripheral vascular disease.
Modifications in transcutaneous oxygen pressure (TcPO2), induced by the administration of 3 mg/kg/day buflomedil chlorhydrate for seven days were evaluated in 12 subjects suffering from peripheral vascular disease (PVD). After the treatment a significant increase in TcPO2 basal values was observed in Stage III and Stage IV PVD patients (+32.2%) while a significant reduction of 12% in the half-recovery time to basal values after an induced ischemia was recorded in Stage II PVD patients by the seventh day. Buflomedil did not, however, cause any significant variations in the ankle/arm pressure ratio or in the plethysmographic peak flow.


Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation.
Interleukin 4 (IL-4) exerts a decisive role in the coordination of protective immune responses against parasites, particularly helminths. A disregulation of IL-4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human IL-4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the IL-4 receptor (IL-4R(ex)). In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T-cell proliferation and B-cell CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type). IL-4 variants affected at site 2 exhibited partial agonist activity during T-cell proliferation; however, they still bound with high affinity to IL-4R(ex). [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO J., 11, 3237-3244)]. These findings indicate that IL-4 functions by binding IL-4R(ex) via site 1 which is constituted by residues on helices A and C.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto.
Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. We evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD groups. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. A significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 μg/mL ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 μg/mL ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 μg/mL ABZ-β-CD compared to ABZ alone. This provides new insights into the use of nanostructured β-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.


Report of the 48th Annual Meeting of the Pacific Association of Pediatric Surgeons, Jeju, South Korea, May 17th-21st, 2015.
This is the report of the 48th Annual Meeting of the Pacific Association of Pediatric Surgeons held at the Shilla Hotel, Jeju Island, South Korea, May 17th-21st, 2015.


Analysis of two transcript isoforms of vacuolar ATPase subunit H in mouse and zebrafish.
ATP6V1H encodes the subunit H of vacuolar ATPase (V-ATPase) and has been recently proved to regulate osteoclast function. The alternative splicing of ATP6V1H gene results in two isoforms, and it is not clear whether and how the two isoforms function differently. In this report, we used bioinformatics methods to compare the differences of two isoforms in different species. The distributions and amounts of two isoforms were analyzed in eleven kinds of mouse tissues and mouse osteoclasts using RT-PCR, Q-PCR, western blot and immunohistochemical staining methods, respectively. In order to observe the in vivo biological differences of two isoforms during development, the zebrafish mRNA of two wild type atp6v1h transcripts as well as their mutant forms were also injected into zebrafish embryos, respectively. Bioinformatic analysis revealed that two isoforms were quite different in many ways, especially in protein size, internal space, phosphorylation state and H-bond binding. The amounts of two transcripts and the ratio of long and short transcript varied a lot from tissue to tissue or cell to cell, and osteoclasts were the cells only expressing long isoform among the tissues or cells we detected. The in vivo selective expression of two subunit H splice variants showed their different effects on the craniofacial development of zebrafish. The short isoform reduced the size of zebrafish head and did not play a complete function compared with the long isoform. We propose that long isoform of subunit H is necessary for the normal craniofacial bone development and the lack of short transcript might be necessary for the normal osteoclastic function.


Health policy: Reducing rheumatic heart disease in Africa -- time for action.
Rheumatic heart disease (RHD) key opinion leaders, health ministers, clinicians, and industry representatives gathered in Ethiopia in February 2015. The question: how to eradicate RHD in Africa. The response: the Addis Ababa communiqué, a practical document outlining seven major barriers to RHD control in Africa and seven strategies to address them.


PIPER: A logic-driven deep contrastive optimization pipeline for event temporal reasoning.
Event temporal relation extraction is an important task for information extraction. The existing methods usually rely on feature engineering and require post-process to achieve optimization, though inconsistent optimization may occur in the post-process module and main neural network due to their independence. Recently, a few works start to incorporate the temporal logic rules into the neural network and achieve joint optimization. However, these methods still suffer from two shortcomings: (1) Although the joint optimization is applied, the differences between rules are neglected in the unified design of rule losses and further the interpretability and flexibility of the design of model are reduced. (2) Because of lacking abundant syntactic connections between events and rule-match features, the performance of the model may be suppressed by the inefficient interaction in training between features and rules. To tackle these issues, this paper proposes PIPER, a logic-driven deep contrastive optimization pipeline for event temporal reasoning. Specifically, we apply joint optimization (including multi-stage and single-stage joint paradigms) by combining independent rule losses (i.e., flexibility) to make PIPER more interpretable. Also, by proposing a hierarchical graph distillation network to obtain more abundant syntactic information, the designed rule-match features can effectively aid in the interaction between low-level features and high-level rules during training. The final experiments on TB-Dense and MATRES demonstrate that the proposed model can achieve competitive performance compared with the recent advances.


Chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index in peripheral lymphocytes from 106 control individuals of the U.K. population.
Blood samples were taken from 106 individuals (73 males and 33 females) and examined for chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index (PRI). The values obtained were investigated in relation to sex, age, smoking, alcohol consumption and X-ray exposure. In all the parameters, there was shown to be a difference between the mean values for the males and females. The incidence of chromosome aberrations was greater in females than in the males, whereas the mean values of PRI and mitogen-induced blastogenesis were lower in females than in the males. A sex difference has been reported previously in the same population, in that the females were shown to have a higher rate of sister-chromatid exchanges than the males (Anderson et al., 1986; Dewdney et al., 1986). Contraceptive pill usage was not considered to be of importance in the sex difference seen and there was shown to be no significant influence due to age, smoking or alcohol consumption on any of the parameters except that smoking reduced lymphocyte PRI. Males with previous X-ray exposure also showed a lower response to mitogen-induced blastogenesis and had a reduced PRI.


Prognostic Implications of Comprehensive Whole Vessel Plaque Quantification Using Coronary Computed Tomography Angiography.
The prognostic value of whole vessel plaque quantification has not been fully understood. We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed tomography angiography. In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area <4 mm2, plaque burden ≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume ≥306.5 mm3, fibrofatty and necrotic core volume ≥4.46 mm3, or percent total atheroma volume ≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models. Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P < 0.001) in predicting FFR ≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95% CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P < 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not. Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163).


Metabolism of benzo[c]phenanthrene by rat liver microsomes and by a purified monooxygenase system reconstituted with different isozymes of cytochrome P-450.
Metabolism of the environmental pollutant and weak carcinogen benzo[c]-phenanthrene (B[c]Ph) by rat liver microsomes and by a purified and reconstituted cytochrome P-450 system is examined. B[c]Ph proved to be one of the best polycyclic aromatic hydrocarbon substrates for rat liver microsomes. It is metabolized by microsomes from control rats and by rats treated with phenobarbital or 3-methylcholanthrene at 3.9, 4.2 and 7.8 nmol/nmol cytochrome P-450/min, respectively. Principal metabolites are dihydrodiols along with small amounts (less than 10%) of phenols. The K-region 5,6-dihydrodiol is the major metabolite and accounts for 77-89% of the total metabolites. The 3,4-dihydrodiol with a bay-region 1,2-double bond is formed in much smaller amounts and accounts for only 6-17% of the total metabolites, the highest percentage being formed by microsomes from control rats. Highly purified monooxygenase systems reconstituted with cytochrome P-450a, P-450b and P-450c and epoxide hydrolase form predominantly the 5,6-dihydrodiol (95-97% of total metabolites) and only a small percentage of the 3,4-dihydrodiol (3-5% of total metabolites). The 3,4-dihydrodiol is formed with higher enantiomeric purity by microsomes from 3-methylcholanthrene-treated rats (88%) than by microsomes from control rats (78%) or phenobarbital-treated rats (60%). In each case the (3R,4R)-enantiomer predominates. B[c]Ph 5,6-dihydrodiol formed by all three microsomal preparations is nearly racemic.


Prediction of incomplete primary debulking surgery in patients with advanced ovarian cancer: An external validation study of three models using computed tomography.
To test the ability of three prospectively developed computed tomography (CT) models to predict incomplete primary debulking surgery in patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer. Three prediction models to predict incomplete surgery (any tumor residual >1cm in diameter) previously published by Ferrandina (models A and B) and by Gerestein were applied to a validation cohort consisting of 151 patients with advanced epithelial ovarian cancer. All patients were treated with primary debulking surgery in the Eastern part of the Netherlands between 2000 and 2009 and data were retrospectively collected. Three individual readers evaluated the radiographic parameters and gave a subjective assessment. Using the predicted probabilities from the models, the area under the curve (AUC) was calculated which represents the discriminative ability of the model. The AUC of the Ferrandina models was 0.56, 0.59 and 0.59 in model A, and 0.55, 0.60 and 0.59 in model B for readers 1, 2 and 3, respectively. The AUC of Gerestein's model was 0.69, 0.61 and 0.69 for readers 1, 2 and 3, respectively. AUC values of 0.69 and 0.63 for reader 1 and 3 were found for subjective assessment. Models to predict incomplete surgery in advanced ovarian cancer have limited predictive ability and their reproducibility is questionable. Subjective assessment seems as successful as applying predictive models. Present prediction models are not reliable enough to be used in clinical decision-making and should be interpreted with caution.


Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.
Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.


Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study.
Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.


Is 'likely pathogenic' really 90% likely? Reclassification data in ClinVar.
In 2015, professional guidelines defined the term 'likely pathogenic' to mean with a 90% chance of pathogenicity. To determine whether current practice reflects this definition, ClinVar classifications were tracked from 2016 to 2019. During that period, between 83.8 and 99.1% of likely pathogenic classifications were reclassified as pathogenic, depending on whether LP to VUS reclassifications are included and on how these classifications are categorized.


BRAF V600E mutation in neocortical posterior temporal epileptogenic gangliogliomas.
The aim of this study was to verify the presence of BRAF mutations in a series of six patients affected by drug-resistant focal epilepsy associated with neocortical posterior temporal gangliogliomas (GG) who were subjected to lesionectomy between June 2008 and November 2013. GG are an increasingly recognized cause of epilepsy and represent the most common tumor in young patients undergoing surgery for intractable focal epilepsy. BRAF mutations have been identified in up to 50% of GG. Interestingly, these six patients shared a specific anatomical posterior temporal site. In all patients, histological examination confirmed the diagnosis of GG, and two were also associated with a focal cortical dysplasia (FCD) type IIa. BRAF mutations were found in four out of six GG (66.6%). Furthermore, dysplastic tissue of Patient 2 showed a concomitant BRAF V600E mutation. All patients but one (83.3%) achieved Engel Class Ia seizure control. The patient carrying a concomitant BRAF mutation in GG and FCD fell into Engel Class II. Further analyses will be required in order to better understand the meaning of BRAF mutations in epilepsy-associated tumors and FCD and their possible role as a prognostic seizure outcome and tumor behavior marker.


Foreign Body in the Airway a Female Patient with Myasthenia Gravis.
Aspiration of a foreign body occurs rarer in adults than it does in children. Advanced age and swallowing disorders, often caused by neuromuscular diseases, predispose for aspiration. Symptoms due to aspiration are mainly cough and wheezing. However, clinical and radiological symptoms may mistakenly suggest lung cancer. Making a proper diagnosis could be difficult and time consuming. In this study we report a case of a 73-year old woman who has been diagnosed and treated myasthenia gravis for 10 years. The patient manifested chronic cough for over a year, weight loss, lung lesions on chest X-ray and computed tomography images in the form of atelectasis and inflammatory infiltrations. The results of cytological tests of bronchoalveolar lavage fluid were 'atypical cells' which suggested a lung cancer. Flexible bronchoscopy set the diagnosis as a foreign body in right upper bronchus, which turned out to be a piece of a plant obstructing the bronchus. The patient came down with pneumonia. Laboratory examinations revealed leucocytosis and a high level of C-reactive protein. A complete removal of foreign body took place during rigid bronchoscopy. Concomitantly, but unrelated to the finding of a foreign body in the bronchus, the patient was diagnosed with digestive tract perforation on the basis of X-ray images, which remained otherwise asymptomatic. Explorative laparotomy revealed a perforated colonic diverticulum, which was successfully treated surgically.


Computational Modeling of Antibody and T-Cell Receptor (CDR3 Loops).
Antibodies and T-cell receptors have been a subject of much interest due to their central role in the immune system and their potential applications in several biotechnological and medical applications from cancer therapy to vaccine development. A unique feature of these two lymphocyte receptors is their ability to bind a huge variety of different (pathogen) targets. This ability stems from six short loops in the binding domain that have hypervariable sequence due to genetic recombination mechanism. Particularly one of these loops, the third complementarity determining region (CDR3), has the highest sequence variability and a dominant role in binding the target. However, it has also been proven the most difficult to be modeled structurally, which is vitally important for downstream tasks such as binding prediction. This difficulty stems from its variability in sequence that both reduces the possibility of finding homologues and introduces unique structural features in the loop. We present here a general protocol for modeling such loops in antibodies and T-cell receptors. We also discuss the difficulties in loop modeling and the advantages and limitations of different modeling methods.


[The costimulating effect of chorionic gonadotropin on lymphokine-activated splenocytes. A new aspect of the immunomodulating action of the pregnancy hormone].
An immunodepressive effect of chorionic gonadotropin (CG) low (40IU) and high (200IU) doses on the processes of lymphocyte antigen-independent differentiation, realizing the primary immune response has been established in the short-term culture of mice splenic intact cells. Splenocyte activation by Con-A or human recombinant IL-2 does not show an expressive immunostimulating effect on the processes of plaque forming cells (PFC) formation. While the immunomodulating effect of CG on the background of these activators changes. In the presence of Con-A or IL-2, hormone in the dose of 40 IU can't effectively suppress the PFC formation processes. On the background of IL-2, CG-200IU shows an expressed opposite effect, increasing the splenocyte ability to form PFC twice as much. It is suggested, that CG appears to be a cofactor, intensifying the processes of immunocompetent cell proliferation and differentiation, connected with this lymphokine. A new aspect of the CG immunomodulating effect during pregnancy is being discussed now.


Development of technologies for placement of perineural catheters.
Continuous peripheral nerve block (CPNB) success is largely dependent on placement of the catheter close enough to the nerve to allow effective and sustained analgesia following painful surgeries with a minimum volume of local anesthetic. One of the most common problems associated with CPNB involves accurate placement of the catheter tip, migration, and dislodgement of the catheter. This is of increasing importance now that catheters are left in place for prolonged periods of time to provide postoperative analgesia, and patients with peripheral nerve catheters are being discharged home with ambulatory pumps. In response to the challenges of providing safe, effective, and consistently reliable analgesia, research and development in this field is expanding rapidly. This review article presents results from recent publications addressing the subject of peripheral nerve catheter localization.


Impacts of historical warming on marine fisheries production.
Climate change is altering habitats for marine fishes and invertebrates, but the net effect of these changes on potential food production is unknown. We used temperature-dependent population models to measure the influence of warming on the productivity of 235 populations of 124 species in 38 ecoregions. Some populations responded significantly positively (n = 9 populations) and others responded significantly negatively (n = 19 populations) to warming, with the direction and magnitude of the response explained by ecoregion, taxonomy, life history, and exploitation history. Hindcasts indicate that the maximum sustainable yield of the evaluated populations decreased by 4.1% from 1930 to 2010, with five ecoregions experiencing losses of 15 to 35%. Outcomes of fisheries management-including long-term food provisioning-will be improved by accounting for changing productivity in a warmer ocean.


Hepatocellular hypertrophy and cell proliferation in Sprague-Dawley rats from dietary exposure to potassium perfluorooctanesulfonate results from increased expression of xenosensor nuclear receptors PPARα and CAR/PXR.
The present study investigated the potential role for activation of PPARα and CAR/PXR by potassium PFOS (K⁺ PFOS) with respect to the etiology of hepatic hypertrophy and hepatocellular adenoma in rats. Male Sprague-Dawley rats were fed K⁺ PFOS (20 or 100 ppm) for either 1, 7, or 28 days. Wyeth 14,643 (Wy 14,643, 50 ppm) and phenobarbital (PB, 500 ppm) were the controls for PPARα and CAR/PXR activation, respectively. Measurements included: plasma ALT, AST, cholesterol, triglycerides, and glucose; liver protein and DNA content; liver activities of palmitoyl CoA oxidase (ACOX), Cyp4A, CYP2B, and CYP3A; induction of liver CYP4A1, CYP2E1, CYP2B1/2, and CYP3A1 proteins (SDS-PAGE and Western blots); liver and thyroid microscopic histopathology, apoptotic index, and cell proliferation index. Terminal body weight was decreased by K⁺ PFOS (100 ppm) and Wy 14,643. All test-compound treatments increased liver weight. Plasma lipids were decreased by both PFOS and Wy 14,643. After treatment for 1 day, K⁺ PFOS (100 ppm), PB, and Wy 14,643 increased mean hepatic DNA concentration and total hepatic DNA, and total DNA remained elevated after treatment for 7 days and 28 days (PB and Wy 14,643 only). Hepatic P450 concentration was elevated after 7 and 28 days by K⁺ PFOS and by PB. K⁺ PFOS and Wy 14,643 increased liver activities of ACOX and CYP4A as well as increased liver CYP4A1 protein. By 28 days of treatment, K⁺ PFOS and PB increased liver activities of CYP2B and CYP3A as well as increased liver CYP2B1/2 and CYP3A1 proteins, and Wy 14,643 increased CYP2B enzyme activity to a slight extent. All test compounds increased the liver cell proliferative index and decreased the liver apoptotic index. No histological changes of the thyroid were noted; however, PB and WY increased thyroid follicular cell proliferation index (seven-day treatment only), while K⁺ PFOS did not. The thyroid follicular cell apoptotic index did not differ between groups. The hepatomegaly and hepatocellular adenoma observed after dietary exposure of Sprague-Dawley rats to K⁺ PFOS likely are due to the increased expression of xenosensor nuclear receptors PPARα and CAR/PXR. Given the markedly lower or absent response of human hepatocytes to the proliferative stimulus from activation of PPARα and CAR/PXR, the hepatocellular proliferative response from activation of these receptors by PFOS observed in rats is not expected to be of human relevance.


CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals.
The role of genetic polymorphisms in cytochrome (CYP) 2D6 involved in the metabolism of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy) is unclear. Effects of genetic variants in CYP2D6 on the pharmacokinetics and pharmacodynamic effects of MDMA were characterized in 139 healthy individuals (70 men, 69 women) in a pooled analysis of eight double-blind, placebo-controlled crossover studies. In CYP2D6 poor metabolizers, the maximum concentrations (Cmax) of MDMA and its active metabolite 3,4-methylene-dioxyamphetamine were +15 and +50% higher, respectively, compared with extensive metabolizers and the Cmax of the inactive metabolite 4-hydroxy-3-methoxymethamphetamine was 50-70% lower. Blood pressure and subjective drug effects increased more rapidly after MDMA administration in poor metabolizers than in extensive metabolizers. In conclusion, the disposition of MDMA and its effects in humans are altered by polymorphic CYP2D6 activity, but the effects are small because of the autoinhibition of CYP2D6.


Fine structure of serotonin-containing axons in the marginal zone of the rat spinal cord.
Descending serotoninergic systems in the spinal cord may be involved in antinociception. In this study 6 rat spinal cords were prepared for serotonin immunostaining and marginal zones (lamina I of Rexed) from the dorsal horn were examined with electron microscopy. Stained terminals were often seen to be closely associated with the somata of lamina I neurones or other unstained axon terminals, but seldom formed conventional synaptic junctions. It is concluded that serotoninergic systems in this region may influence the activity of these associated structures in a diffuse non-synaptic manner.


Stimulation of breathing movements by L-5-hydroxytryptophan in fetal sheep during normoxia and hypoxia.
1. In fetal lambs in late gestation, systemic infusion of L-5-hydroxytryptophan (L-5-HTP) during normoxia greatly increases the incidence of fetal breathing movements (FBM) and high-voltage electrocortical activity (HV ECoG). It also induces FBM during HV ECoG and increases blood pressure. To investigate its mechanism of action, L-5-HTP was administered in conjunction with the 5-hydroxy-tryptamine (5-HT) antagonists ketanserin or cyproheptadine. L-5-HTP was also infused with or without the antagonists during hypoxia, to test whether it would overcome the inhibition of FBM by hypoxia. 2. When L-5-HTP was given in normoxia, cyproheptadine blocked and ketanserin reduced the increase in blood pressure, both drugs blocked the stimulation of FBM, but neither drug prevented the induction of prolonged episodes of HV ECoG. 3. In hypoxia, L-5-HTP similarly stimulated FBM. This effect was also blocked by cyproheptadine and was delayed by ketanserin. 4. The antagonism of the effects of L-5-HTP on blood pressure and the incidence of FBM in normoxia and hypoxia is consistent with the action of L-5-HTP via 5-HT receptors. At present there is no clear explanation of the mechanism by which L-5-HTP induces HV ECoG.


Tough Decisions During the COVID 19 Pandemic: A Frail Latino Patient.
The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had overwhelmed the healthcare system worldwide with multiple ethical dilemmas. Several tools have been used to assess risk factors in these patients. One of them, the Clinical Frailty scale, has shown good correlation between the patient functional status and hospital stay with overall mortality. We present a case were the Clinical Frailty Scale was used to assess patient management and goals of care.


Fatty acid and sterol synthesis by rat small intestine in vitro.
Slices of rat jejunum were incubated with [2(-14)C] pyruvate, [1(-14)C] acetate, or [3H]H2O to determine lipogenic activity. Under all conditions studied, pyruvate acted as a better precursor than acetate for fatty acid synthesis but not for the synthesis of sterol. Exogenous glucose significantly (P less than or equal to 0.05) increased the conversion of both pyruvate and acetate to fatty acids. By contrast fasting resulted in a decrease (p less than or equal to 0.05) in lipogenic activity. The highest levels of lipogenesis were observed when [3H]H2O + glucose at a concentration of 20 mM was used. From such experiments, the absolute rate of fatty acid synthesis in the tissue preparation was calculated: 734 +/- 54 nmoles acetyl units incorporated into fatty acids/g tissue/hr.


Enhanced efficiency in hollow core electrospun nanofiber-based organic solar cells.
Over the last decade, nanotechnology and nanomaterials have attracted enormous interest due to the rising number of their applications in solar cells. A fascinating strategy to increase the efficiency of organic solar cells is the use of tailor-designed buffer layers to improve the charge transport process. High-efficiency bulk heterojunction (BHJ) solar cells have been obtained by introducing hollow core polyaniline (PANI) nanofibers as a buffer layer. An improved power conversion efficiency in polymer solar cells (PSCs) was demonstrated through the incorporation of electrospun hollow core PANI nanofibers positioned between the active layer and the electrode. PANI hollow nanofibers improved buffer layer structural properties, enhanced optical absorption, and induced a more balanced charge transfer process. Solar cell photovoltaic parameters also showed higher open-circuit voltage (+ 40.3%) and higher power conversion efficiency (+ 48.5%) than conventional architecture BHJ solar cells. Furthermore, the photovoltaic cell developed achieved the highest reported efficiency value ever reached for an electrospun fiber-based solar cell (PCE = 6.85%). Our results indicated that PANI hollow core nanostructures may be considered an effective material for high-performance PSCs and potentially applicable to other fields, such as fuel cells and sensors.


Identification of a polysaccharide produced by the pyruvate overproducer Candida glabrata CCTCC M202019.
Candida glabrata has great potential for the accumulation of pyruvate as a preferred strain in pyruvate production by fermentation. However, its substrate conversion rate is relatively low. In this study, a novel polysaccharide containing α-1,4-glucosidic bonds was observed accidentally in screening a high-titer pyruvate strain by atmospheric and room temperature plasma mutagenesis of C. glabrata. Chemical analysis of the partially purified polysaccharide S4-C10 showed the main components were 1.2% (w/w) protein and 94.2% (w/w) total sugar. Fourier transform infrared and molecular mass distribution analysis indicated that the main component (PSG-2) of S4-C10 was a small molecular homogeneous protein-bound polysaccharide. Monosaccharide analysis of PSG-2 showed it consisted of glucose, mannose, and fructose. By optimizing the vitamin mix content, 77.6 g L-1 S4-C10 polysaccharide could be obtained after 72 h fermentation at 30 °C in 500-mL flasks. RT-qPCR analysis showed that transcriptional level of some key genes related to polysaccharide biosynthesis was upregulated compared to that of wild-type strain. By knocking out two most significantly upregulated genes, CAGL0H02695g and CAGL0K10626g, in the wild-type strain, the pyruvate consumption rate was significantly reduced in late pyruvate fermentation phase, while the titer of polysaccharides was reduced by 18.0%. Besides the potential applications of the novel identified polysaccharide, this study provided clues for increasing the conversion ratio of glucose to pyruvate in C. glabrata by further decreasing the accumulation of polysaccharides.


Geographic variation and trends in prevalence of obesity among US adolescents, 2016-2021.
Recent updates of geographic variations, trends, and sociodemographic disparities in obesity prevalence among US adolescents are limited. The study aimed to fill those research gaps. Serial cross-sectional analysis of the US nationally representative study. Data from six cycles of the National Survey of Children's Health (2016, 2017, 2018, 2019, 2020, and 2021) with information on physical health at the national and state level were used. A total of 107,274 adolescents aged 10-17 years old were included with sociodemographic data (age, sex, race/ethnicity, parental education level, and family income) and state of residence. Logistic regression models were used to estimate the odds ratios (ORs) associated with obesity across sociodemographic groups. In addition, ORs were calculated to compare obesity rates between the pandemic period (2020-2021) and the pre-pandemic period (2018-2019) overall and by sociodemographic subgroups. Survey analysis procedures were used to account for complex survey designs to derive representative estimates. From 2016 to 2021, obesity prevalence increased from 16.1% (95% confidence interval [CI], 14.9%-17.4%) to 17.6% (95% CI, 16.4%-18.9%) (P-trend = 0.04). The combined prevalence of obesity varies substantially by state, from 9.34% (95% CI, 6.96%-12.4%; Colorado) to 27.1% (95% CI, 23.1%-31.5%; Mississippi) for adolescents aged 10-13 years and ranged from 9.86% (95% CI, 7.63%-12.7%; Utah) to 22.4% (95% CI, 19.0%-26.1%; West Virginia) for adolescents aged 14-17 years. Except for subgroups male gender and parents with college degrees or above, the prevalence of obesity showed stable trends across sociodemographic subgroups. Compared to the pre-pandemic period, the multivariable-adjusted ORs of obesity were 1.18 (95% CI, 1.06-1.32) for male adolescents, 1.16 (95% CI, 1.04-1.28) for non-Hispanic White adolescents, 1.81 (95% CI, 1.15-2.84) for non-Hispanic Asian adolescents, 1.26 (95% CI, 1.05-1.52) for adolescents whose parents had a high school education, and 1.15 (95% CI, 1.0-1.33) for adolescents whose parents had a college degree or higher. The prevalence of obesity among US adolescents increased significantly between 2016 and 2021. The prevalence of obesity was relatively high in southern states. Those with low household income, low parental education, or being non-Hispanic Black or Hispanic were also more likely to be obese. Compared to the pre-pandemic period, several groups of adolescents increased their likelihood of obesity during the pandemic period.


Isonicotinic acid hydrazide as an antigen.
Detection by in vitro serologic techniques of circulating antibody directed against isonicotinic acid hydrazide (INH, known as isoniazid) in humans has not been reported. In the past few months, however, sera from a patient with a recent history of isoniazid hypersensitivity of the immediate type have been studied, and reaginic antibodies (IgE) specific to INH were detected by means of an enzyme-linked allergosorbent test. Preliminary enzyme-linked allergosorbent tests also demonstrated that INH-specific IgE occurred in the serum of two of 150 patients with tuberculosis who had been treated with INH.


First evidence of sucrose biosynthesis by single cyanobacterial bimodular proteins.
The net synthesis of sucrose (Suc) is catalysed by the sequential action of Suc-phosphate synthase (SPS) and Suc-phosphate phosphatase (SPP). SPS and SPP from Anabaena sp. PCC 7120 (7120-SPS and 7120-SPP) define minimal catalytic units. Bidomainal SPSs, where both units are fused, occur in plants and cyanobacteria, but they display only SPS activity. Using recombinant proteins that have fused 7120-SPS and 7120-SPP, we demonstrated that they are bifunctional chimeras and that the arrangement 7120-SPS/SPP is the most efficient to catalyse the sequential reactions to yield Suc. Moreover, we present the first evidence of a bidomainal SPS present in the cyanobacterium Synechococcus elongatus PCC 7942 with both, SPS and SPP activity.


Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus.
Early surgical series of shunt insertion for idiopathic normal-pressure hydrocephalus reported a low rate of short-term improvement with a relatively high rate of mortality and morbidity; subsequently shunt insertion was recommended for patients in whom there is favourable risk-to-benefit ratio. Bibliographic search for studies that objectively assessed the outcome following shunt insertion in idiopathic normal-pressure hydrocephalus was done; the aim was to estimate the outcome of shunt insertion in terms of improvement rates and associated mortality and morbidity. A total of 64 studies of 3,063 patients were reviewed. Positive improvement following shunt insertion was reported in an average of 71 % of patients with an average 1 % mortality. Results from studies published in the last 5 years showed 82 % improvement following shunt insertion, mortality of 0.2 %, and combined common complications rate of 8.2 %. When patients are properly selected, shunt insertion is a safe and effective management of idiopathic normal-pressure hydrocephalus with a prolonged positive outcome.


Effects of soil factors on dimethyl disulfide desorption and the risk of phytotoxicity to newly-planted seedlings.
Dimethyl disulfide (DMDS) is a relatively new soil fumigant used in agro-industrial crop production to control soil-borne pests that damage crops and reduce yield. The emissions of DMDS after fumigation reduce soil concentrations thus reducing the risk of phytotoxicity to newly planted crops. However, the factors affecting the desorption of DMDS from soil are unclear. In our study, the desorption characteristics of DMDS from soil were measured in response to continuous ventilation. The degradation of DMDS in soil was examined by thermal incubation. The phytotoxic response of newly-planted cucumber (Cucumis sativus) seedlings to DMDS residues was measured by a sand culture experiment. The results showed DMDS desorption and degradation rates fit a first-order model; that 92% of the DMDS desorption occurred in the first hour after fumigant application; and that residue concentrations in the soil at the end of the ventilation period were unlikely to be phytotoxic to newly-planted cucumber seedlings. By the third day of ventilation, the average desorption rate (ADR) of DMDS in Wenshan soil was 4.0 and 3.6 times, respectively, faster than that in Shunyi and Suihua soils and the ADR of DMDS in soil decreased by 40.0% when the soil moisture content increased from 3% to 12% (wt/wt). Moreover, within one hour of ventilation, the ADR of DMDS in soil decreased by 20.1% when the soil bulk density increased from 1.1 to 1.3 g cm-3. The degradation of DMDS in soil, however, was mostly influenced by soil type and moisture content. A slow degradation rate resulted in a high initial desorption concentration of DMDS in soil. Our results indicated that DMDS desorption from soil in response to continuous ventilation was affected by the soil type, moisture content and bulk density. Rapid degradation of DMDS in soil will lower the risk of phytotoxic residues remaining in the soil and reduce emissions during the waiting period. Acceleration of emissions early in the waiting period by managing soil moisture content or increasing soil porosity may shorten the duration of emissions. Alternatively, soil extraction technology could be developed to recover and reduce fumigant emissions.


Simultaneous liquid chromatographic determination of lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in plasma of patients with epilepsy.
A very simple and fast method has been developed and validated for simultaneous determination of the new generation antiepileptic drugs (AEDs) lamotrigine (LTG), oxcarbazepine's (OXC) main active metabolite monohydroxycarbamazepine and felbamate in plasma of patients with epilepsy using high-performance liquid chromatography (HPLC) with spectrophotometric detection. Plasma sample (500 microL) pre-treatment was based on simple deproteinization by acetonitrile. Liquid chromatographic analysis was carried out on a Synergi 4 microm Hydro-RP, 150 mm x 4 mm I.D. column, using a mixture of potassium dihydrogen phosphate buffer (50mM, pH 4.5) and acetonitrile/methanol (3/1) (65:35, v/v) as the mobile phase, at a flow rate of 1.0 mL/min. The UV detector was set at 210 nm. Calibration curves were linear (mean correlation coefficient >0.999 for all the three analytes) over a range of 1-20 mg/mL for lamotrigine, 2-40 microg/mL for monohydroxycarbamazepine and 10-120 microg/mL for felbamate. Both intra and interassay precision and accuracy were lower than 7.5% for all three analytes. Absolute recoveries ranged between 100 and 104%. The present procedure describes for the first time the simultaneous determination of these three new antiepileptic drugs. The simple sample pre-treatment, combined with the fast chromatographic run permit rapid processing of a large series of patient samples.


Differences in the N termini of herpes simplex virus type 1 and 2 gDs that influence functional interactions with the human entry receptor Nectin-2 and an entry receptor expressed in Chinese hamster ovary cells.
Amino acid differences at seven positions in the N termini of the glycoproteins D (gDs) specified by herpes simplex virus type 1 (HSV-1) and HSV-2 are largely responsible for the significantly higher cell fusion activity of HSV-2 gD with Chinese hamster ovary cells expressing human nectin-2 or only an endogenous hamster receptor.


Association of Epidermal Biophysical Properties with Obesity and Its Implications.
Obesity is a condition defined by an excess amount of body fat, with body mass index (BMI) of 30 and higher. It is associated with a number of other medical conditions, including insulin resistance, diabetes mellitus, and cardiovascular diseases, as well as dyslipidemia, and it is also associated with several cutaneous disorders such as atopic dermatitis, psoriasis, intertriginous dermatitis, acanthosis nigricans and skin infections. Evidence suggests a link between obesity and epidermal dysfunction. Generally, individuals with obesity display higher transepidermal water loss rate and lower stratum corneum hydration levels, although no association of obesity with epidermal dysfunction has been documented. Results of skin surface pH are controversial. But study demonstrated a positive correlation of BMI with skin surface pH on both the forearm and the shin in males, suggesting that the changes in epidermal function vary with gender in individuals with obesity. This review summarizes the association between obesity and epidermal function, and discusses possible underlying mechanisms. Individuals with obesity exhibit poor epidermal permeability barrier and lower stratum corneum hydration levels. Because of the pathogenic role of compromised epidermal function in inflammation, which is also linked to obesity, improvement in epidermal function could benefit individuals with obesity, particularly those with abnormalities in epidermal function.


Comparison of different medical cases in urinary arsenic speciation by fast HPLC-ICP-MS.
The inorganic arsenic species As(III), As(V) and the organic species methylarsonate (MMA(V)), dimethylarsinate (DMA(V)) and arsenobetaine (AsB) were determined in human urine by a fast anion exchange HPLC-ICP-MS method, which was developed for clinical laboratories with high sample throughput. This paper compares typical chromatograms of the arsenic species in urine samples collected in different medical cases, for example, for the non-exposed population, for environmentally (plant protectants) and occupationally (glass manufacture) exposed persons, for a person after a failed suicide attempt with As2O3 and for persons before and after administration of the antidot sodium 2,3-dimercapto-1-propane-sulfonate (DMPS). Concentration data of the urinary As species for the non-exposed German population (n=82) are compared with the concentrations before and after administration of DMPS (n=37). For the non-exposed group the toxicologically relevant As in urine consists of 81% DMA(V), 10% MMA(V) and 9% inorganic As. However, a few hours after an acute intoxication with inorganic As this distribution changes dramatically and As(III) and As(V) are predominantly found in urine. After treatment with DMPS the total As concentration increases significantly and mainly MMA(V) and As(III) were found in urine samples.