Changes in HDL subfractions after a single, extended episode of physical exercise.
In order to investigate the changes in HDL subfractions induced by a single period of extended physical exercise, 9 endurance-trained adults were examined before and 6 min, 1 and 6 h after a 30 km cross-country race. In contrast to less evident changes in the concentrations of total HDL, apolipoprotein A-I and A-II, there were significant changes in HDL subfractions. Resting levels of protein and cholesterol content of the HDL subfractions 1-3 increased (subfraction 1, density gradient 1.093: 1.68 +/- 0.58 to 3.24 +/- 0.86 mmol/1 cholesterol, P less than 0.001), while the concentrations in HDL subfractions 11-12 decreased proportionately (subfraction 12, density gradient 1.142: 3.68 +/- 0.81 to 2.19 +/- 0.22 mmol/1 cholesterol, P less than 0.001). The results suggest that physical exercise induces an increased formation of HDL particles of lower density from HDL particles of higher density. It was concluded that this formation is related to the catabolism of triglyceride-rich lipoproteins in the post-exercise period.


Invasive aspergillosis treated with adjunctive hyperbaric oxygenation: a retrospective clinical series at a single institution.
Invasive aspergillosis is the leading cause of early death in many transplant centers and has a major impact on the management of hematologic malignancies. The mortality rate with current therapy (amphotericin B and surgery) has remained unacceptably high. In vitro data along with a few case reports have suggested a potential benefit of hyperbaric oxygen (HBO). We retrospectively studied all patients referred to our service when histologic specimens suggested invasive aspergillosis. Our main assessment of outcome was survival 3 months after initiation of HBO. Ten patients were included. All received adjunctive HBO along with the standard of care. Rhinosinusinal infection was the primary presentation. The most common underlying conditions were hematologic malignancies. Six patients were free of signs of infection 3 months after the first HBO treatment. Adjunctive HBO appears to be a valuable tool in this devastating condition. Further studies are warranted to clarify its role.


Cardiovascular risk among hypertensive adolescents and the potential benefit of a screen-and-treat strategy.
To evaluate whether screening for hypertension should start early in life, information on the risk of diseases associated with the level of blood pressure in childhood or adolescence is needed. The study by Leiba et al. that is reported in the current issue of Pediatric Nephrology demonstrates convincingly that hypertensive adolescents are at higher risk of cardiovascular death than normotensive adolescents. Nevertheless, it can be shown that this excess risk is not sufficient to justify a screen-and-treat strategy. Since the large majority of cardiovascular deaths occur among normotensive adolescents, measures for primordial prevention of cardiovascular diseases could have a much larger impact at the population level.


In vitro antimicrobial activity of the essential oil from Vanillosmopsis arborea Barker (Asteraceae) and its major constituent, α-bisabolol.
Vanillosmopsis arborea Barker (Asteraceae), commonly known as "candeeiro" is an endemic tree to the Caatinga biome, in northeast Brazil. The major component of its essential oil is α-bisabolol, a monocyclic sesquiterpene alcohol with several biological activities reported. In this study, the antimicrobial activity of the essential oil of V. arborea was investigated in comparison with its major component α-bisabol. The antimicrobial activity was performed against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 12692, Candida albicans (CA) INCQS 40006, Candida krusei (CK) INCQS 40095, Candida tropicalis (CT) INCQS 40042, and multiresistant bacterial strains Staphylococcus aureus 03 and Escherichia coli 08 by the microdilution method and direct contact modulation. The results showed that all strains were sensitive to the samples, except E. coli against the essential oil. Both the essential oil and the α-bisabolol had a synergistic effect against all strains, except for ampicillin against S. aureus 03, which did not show any modifications when combined with the oil. These data show the potential of V. arborea essential oil as an antibiotic modulator as well as a source of bioactive compounds with potential for the development of antimicrobial drugs as well as adjuvant to therapy against these pathogens.


The management of upper airway obstruction in Pierre Robin Sequence.
Pierre Robin Sequence (PRS) is defined by a constellation of characteristics including micrognathia, glossoptosis and airway obstruction. PRS can occur in isolation or can be associated with syndromes and another anomalies. Airway obstruction and feeding difficulties are the major presenting issues, and the severity of the condition ranges from mild, with minimal to no symptoms, to severe, with overt obstruction resulting in apnoeas, severe respiratory distress and cyanosis. The presence of airway obstruction can result in obstructive sleep apnoea and abnormalities in gas exchange, as well as exacerbation of already present feeding difficulties and failure to thrive, secondary to mismatch of caloric intake to energy usage associated with increased effort of breathing. Management of airway obstruction for infants with PRS varies between centres. This paper explores the surgical and non-surgical management options available, their effectiveness and pitfalls in children with PRS. Despite the pros and cons of each management option, it is evident that resource availability and multidisciplinary clinical support are key factors to successful management.


Established and novel initiatives to reduce crowding in emergency departments.
The American College of Emergency Physicians (ACEP) Task Force on Boarding described high-impact initiatives to decrease crowding. Furthermore, some emergency departments (EDs) have implemented a novel initiative we term "vertical patient flow," i.e. segmenting patients who can be safely evaluated, managed, admitted or discharged without occupying a traditional ED room. We sought to determine the degree that ACEP-identified high-impact initiatives for ED crowding and vertical patient flow have been implemented in academic EDs in the United States (U.S.). We surveyed the physician leadership of all U.S. academic EDs from March to May 2010 using a 2-minute online survey. Academic ED was defined by the primary site of an emergency residency program. We had a response rate of 73% (106/145) and a completion rate of 71% (103/145). The most prevalent hospital-based initiative was inpatient discharge coordination (46% [47/103] of respondents) while the least fully initiated was surgical schedule smoothing (11% [11/103]). The most prevalent ED-based initiative was fast track (79% [81/103]) while the least initiated was physician triage (12% [12/103]). Vertical patient flow had been implemented in 29% (30/103) of responding EDs while an additional 41% (42/103) reported partial/in progress implementation. We found great variability in the extent academic EDs have implemented ACEP's established high-impact ED crowding initiatives, yet most (70%) have adopted to some extent the novel initiative vertical patient flow. Future studies should examine barriers to implementing these crowding initiatives and how they affect outcomes such as patient safety, ED throughput and patient/provider satisfaction.


Inflammatory markers of hemogram parameters as predictive factors for disease severity in anti-N-methyl-D-aspartate receptor encephalitis.
This study aimed to investigate the utility of inflammatory markers of hemogram parameters as objective indicators of disease severity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. A total of 98 patients were retrospectively reviewed. Inflammatory markers of hemogram parameters, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio, were acquired within 24 h of admission. We then analyzed their utility as predictive factors for disease severity at different time points assessing with the modified Rankin Scale (mRS). There were 49 patients in the mild group (mRS ≤ 2) and 49 patients in the moderate-to-severe (mRS > 2) group at admission. The moderate-to-severe group presented more frequently with psychiatric symptoms and central hypoventilation, as well as a lower lymphocyte count, a higher neutrophil count, a higher NLR and a higher MLR (all p < 0.05) when compared with the mild group. NLR and MLR showed similar positive correlations with mRS scores (r = 0.40, r = 0.40, both p < 0.001). Further multivariate logistic regression analyses indicated that NLR > 4.232 was an independent risk factor for moderate-to-severe status at admission. Meanwhile, NLR and MLR were associated with disease severity at different stages of follow-up but showed no independent predictive value. Our findings suggested that NLR was an independent risk factor for moderate-to-severe status in the initial stage of anti-NMDAR encephalitis with a cut-off value of > 4.232.


SRD5A3-CDG: a patient with a novel mutation.
Congenital disorders of glycosylation (CDG) are genetic diseases with an extremely broad spectrum of clinical presentations due to defective glycosylation of glycoproteins and glycolipids. Some 45 CDG types have been reported since the first clinical description in 1980. Protein glycosylation disorders are defects in protein N- and/or O-glycosylation. Dolichol phosphate is the carrier of the N-glycan during their assembly first at the outside and subsequently at the inside of the endoplasmic reticulum (ER) membrane, and hence is a key molecule in protein glycosylation. Recently, defects have been identified in the last three steps of the dolichol phosphate biosynthesis: dolicholkinase deficiency (DK1-CDG), steroid 5alpha-reductase type 3 deficiency (SRD5A3-CDG), and dehydrodolichyl diphosphate synthase deficiency (DHDDS-CDG). We report on a patient with SRD5A3-CDG carrying a novel (homozygous) mutation. The diagnostic features of this novel inborn error of glycosylation are psychomotor retardation, nystagmus, visual impairment due to variable eye malformations, cerebellar abnormalities/ataxia, and often ichthyosiform skin lesions.


Single short-term signal that enhances cooperative activity of old rat hepatocytes acts for several days.
Primary cultures of rat hepatocytes were studied in serum-free medium. Ultradian protein synthesis rhythm was used as a marker of overall cell synchronization and cooperation amongst the population. The level of synchronization was determined by amplitudes of the rhythm. Low synchronization of old rat hepatocytes can be enhanced by addition of either gangliosides or phenylephrine to the medium. Incubation of cultures with gangliosides lasted for 2.5 h, while action of phenylephrine was only for 2 min. The amplitude of protein synthesis rhythm was increased 1.5-2 times. In cultures transferred to a fresh normal medium, this increased amplitude was observed for at least 2-3 days. Thus, both gangliosides and phenyleprine are triggers, which, as shown earlier, initiated calcium-dependent processes in the cytoplasm. The results are discussed in the light of concept of the cell self-organization by a direct cell-cell communication.


Insights into Exogenous Tryptophan-Mediated Allosteric Communication and Helical Transition of TRP Protein for Transcription Regulation.
In this study, the binding recognition and allosteric mechanism of tryptophan-responsive regulatory protein (TRP)-DNA and bound exogenous tryptophan (Trp) amino acid complexes for transcriptional regulation were explained through the molecular docking, molecular dynamics (MD), free-energy landscape (FEL), binding free energy (molecular mechanics Poisson-Boltzmann surface area, MMPBSA), and protein structural network (PSN) analyses. The domain transition of helix-turn-helix (HTH) and effector binding domain (EBD) of TRP protein is the vital process for allosteric network communication, DNA recognition, and transcription. TRP protein consists of four putative active site pockets (Act1, Act2, Act3, and Act4) with the binding specificity of exogenous Trp amino acid, which modulates the binding energy of TRP-DNA complexes by conferring the specific residual network and internal helical orientation of DNA-binding domain (DBD) for regulatory mechanism. In the TRP-DNA complex, interaction of Arg28 (helix-1) and Arg36 (helix-2) with the DNA molecule plays a vital role in DNA recognition. As a consequence, allosteric induction of exogenous Trp in the Act3 binding site retains the structural integrity and is quite comfortable with DNA major groove; therefore, it produces less binding energy for complex formation and may involve in oligomeric association for transcription regulation. Meanwhile, Trp in the Act1 binding site induces high helical orientation and fluctuations, leading to dissociation of DNA from the TRP protein. The remaining two complexes of Trp with Act2 and Act4 are predicted to partially affect the transcription mechanism. The present study aims to unravel the role of exogenous Trp amino acid in TRP protein for transcriptional regulatory mechanism.


Early surgical intervention alleviates sensory symptoms following acute traumatic central cord syndrome.
To investigate the impact of early versus delayed surgery on sensory abnormalities in acute traumatic central cord syndrome (ATCCS). Pressure pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM) and pain assessments were performed in 72 ATCCS patients (early vs. delayed surgical treatment: 32 vs. 40) and 72 healthy subjects in this ambispective cohort study. These examinations, along with mechanical detection threshold (MDT) and disabilities of arm, shoulder and hand (DASH), were assessed at 2 years postoperatively. Preoperatively, more delayed surgical patients had neuropathic pain below level compared with early surgical patients (P < 0.05). Both early and delayed surgical patients showed reduced PPT in common painful areas and increased TS, while reduced CPM only existed in the latter (P < 0.05). Reduced PPT in all tested areas, along with abnormalities in TS and CPM, was observed in patients with durations over 3 months. Both incidences and intensities of pain and pain sensitivities in common painful areas were reduced in both treatment groups postoperatively, but only early surgical treatment improved the CPM and TS. Follow-up analysis demonstrated a higher MDT and lower PPT in hand, greater TS, greater DASH, lower pain intensities and higher incidence of dissatisfaction involving sensory symptoms in delayed surgical patients than in early surgical patients (P < 0.05). Central hypersensitivity may be involved in the persistence of sensory symptoms in ATCCS, and this augmented central processing may commence in the early stage. Early surgical treatment may reverse dysfunction of endogenous pain modulation, thus reducing the risk of central sensitization and alleviating sensory symptoms.


Early predictors of success of Kasai operation in children with biliary atresia.
Aim of the study was the evaluation of early predictive parameters of event-free survival (not listed for liver transplantation, not transplanted, no death) in children suffering from biliary atresia after hepatoportoenterostomy (Kasai procedure) in order to optimize pretransplant management. Sixty-seven infants were treated with the Kasai operation at our institution over a 20-year period from 1978 until 1998. Median age at time of operation was 51 days after birth (range 19 - 180 days). Of these 67 infants, 24 children with complete datasets and an observation time of at least one year were evaluated retrospectively using a Cox regression model. The response variable was event-free survival after a median observation time of 4.9 years (1.11- 10.37 years). Six variables were entered as covariates: alanine aminotransferase (ALAT), cholinesterase activity, bilirubin, age at the time of Kasai operation and tracer excretion and uptake during hepatobiliary scintigraphy (HBSS). All variables were evaluated six weeks after operation. For subsequent cut-off determination, a receiver operating analysis (ROC analysis) was carried out. Tracer excretion shown by HBSS showed the highest prognostic power to predict event-free survival after Kasai operation (log rank 18.68, p < 0.0001) followed by bilirubin and ALAT as further significant parameters in the first univariate step of the Cox regression model. In the subsequent multivariate step, the prognostic power of HBSS was improved only by bilirubin (log rank 24.6, p < 0.0001). The ROC analysis determined a cut-off for bilirubin concentrations of 57 micromol/l for event-free survival with a sensitivity of 80 % and a specificity of 78.6 %. The five-year event-free survival-rate was 100 % in the group with good tracer excretion and a bilirubin concentration of 57 micromol/l and 27 % for the other group (log rank test, p < 0. 0001). Early predictors of success of the Kasai operation in children with biliary atresia are free tracer excretion as shown by HBSS and a serum bilirubin concentration < 57 micromol/l six weeks after the operation. Thus, children with bilirubin concentrations above this level should be carefully and frequently monitored with regard to a transplantation requirement in order to optimize pretransplant management.


Sanguis Draconis resin stimulates osteoblast alkaline phosphatase activity and mineralization in MC3T3-E1 cells.
Sanguis Draconis (SD), "Dragon's Blood", is a resin that is obtained from Daemonorops draco (Palmae). Used in traditional medicine, it has shown activity in the prevention of osteoporosis as well as promoting the healing of bone fractures. In this study, the effects of Sanguis Dranonis ethanol extract on β-glycerolphosphate and ascorbic acid induced differentiation using mouse calvaria origin MC3T3-E1 osteoblastic cells was examined. We looked at osteoblast differentiation, proliferation, and mineralization by measuring alkaline phosphatase (ALP) and specific bone marker activities. Osteoblast-like MC3T3-E1 cells were cultured in various concentrations of SD ethanol extract (0.005-1mg/mL) during the osteoblast differentiation period (1, 5, 15, and 25 days). As measured by 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide assay, SD extracts increased cell proliferation as compared to control. The most pronounced effect was observed at the concentration range between 0.01 and 0.1 mg/mL (P<0.01). This SD stimulatory effect for cell proliferation was observed during the whole osteogenic period. Cellular (synthesized) ALP activity was increased during 15 days of culture, and was confirmed by the staining of ALP activity on cell matrix layers for matrix calcification. SD stimulatory effect for cell mineralization we observed in 14 and 21 days. Elevated mRNA or protein levels of bone morphogenetic protein-2(BMP 2), the differentiation marker osteocalcin, osteopontin, collgen I, and a master osteogenic transcription factor, Runx2, were observed in SD-treated cells. These results suggest that SD may increase osteogenic effect by stimulating cell ALP activity and affect the BMP signaling pathway cascades in osteoblastic cells, then promotes osteoblast differentiation, mineralization, and bone formation.


Factors contributing to the inhibition of aspartate aminotransferase by dicarboxylic acids.
At pH 8.0 aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 126.96.36.199) reacts with the modified substrate, erythro-beta-hydroxy-L-aspartate, to form a mixture of enzyme-substrate complexes absorbing at 492 nm. A variety of dicarboxylic acids were studied spectrophotometrically as competitive inhibitors of this reaction. All of the inhibitory dicarboxylic acids form a complex with the enzyme, absorbing at 362 nm. In addition, some of the dicarboxylic acids form a protonated complex absorbing at about 435 nm. This complex, which is the conjugate acid of that absorbing at 362 nm, is formed only by those dicarboxylic acids which can assume a configuration in which the two carboxyl groups are positioned as in maleic acid. Bulky substituents, such as aromatic rings or even methyl groups, prevent the formation of the protonated complex, presumably because of steric restrictions at the active site. Substitution of the central carbon atom of glutaric acid by heteroatoms of increasing charge density results in a progressive decrease in inhibitory effectiveness, at pH 8, primarily due to a loss of this pH-dependent stabilization of the enzyme-dicarboxylic acid complex. Acids with an aromatic ring are among the most potent dicarboxylic acid inhibitors of this enzyme in spite of the fact that they do not undergo the pH-dependent stabilization of their enzyme complexes. From these observations it was concluded that the affinity of aspartate aminotransferase for dicarboxylic acids is determined as much by the mechanism of binding as by the solvation and steric effects.


Mucinous breast carcinoma showing as a cluster of suspicious microcalcifications on mammography.
We report a case of mucinous breast carcinoma whose mammographic features consisted of a suspicious cluster of microcalcifications as the unique sign of malignancy. The lesion was non-palpable and measured approximately 2 cm at the greatest diameter. The microcalcifications showed several morphologies: round, pleomorphic, and fine shapes were identified. The total number of microcalcifications was > 30 and the number per square centimeter varied from 10 to 20. The histological calcifications showed good correlation with the mammographic ones and were localized predominantly at the periphery of the tumor inside ducts with ductal carcinoma in situ or in the acellular mucin. Two types were observed: psammomatous and gross-irregular calcifications. To our knowledge, only one case with similar findings has been reported previously.


Characterization of a new cytotype and ocurrence of a B microchromosome in two spot astyanax, Astyanax bimaculatus Linnaeus, 1758 (Characiformes: Characidae).
Although Astyanax bimaculatus is the most representative species of the genus in the Amazon region, there are no cytogenetic studies of A. bimaculatus species in Amazon region. Thus, we aimed to analyse the chromosome complements of specimens from this area using classic and molecular cytogenetic approaches. The results revealed the existence of a distinct cytotype and this is the first report of the occurrence of a B microchromosome in the species. Overall, these data indicate that the karyotypic evolution of this species is complex, involving the occurrence of chromosomal rearrangements.


Evaluation of the ICD-10 system in coding revascularisation procedures in patients with peripheral arterial disease in England: A retrospective cohort study using national administrative and clinical databases.
Many studies evaluating care in hospitals in England use the Hospital Episode Statistics (HES) administrative database. The aim of this study was to explore whether the International Classification of Diseases 10th Revision (ICD-10) system used by HES supported the evaluation of care received by patients with peripheral arterial disease (PAD) who had revascularisation. This retrospective cohort study used records on patients who had revascularisation for PAD between 1st January 2017 and 31st December 2019 in England, collected prospectively in the National Vascular Registry (NVR) and linked to HES. Patients were excluded if their NVR record did not have a match in HES, due to lack of consent or different admission and procedure dates. Agreement between different presentations of PAD recorded in the NVR and the ICD-10 diagnostic codes recorded in HES was evaluated using the unweighted Kappa statistic and sensitivity and specificity. Agreement between the NVR and HES was also assessed for gender, age, comorbidities, mode of admission, and procedure type and side. In total, 20,603 patients who had 24,621 admissions were included in the study. Agreement between NVR and HES on patient gender (Kappa = 0.98), age (Kappa = 0.98), mode of admission (Kappa = 0.80), and procedure type and side (Kappa = 0.92 and 0.87, respectively) was excellent. When all diagnostic fields in HES were explored, substantial agreement was observed for chronic ischaemia with tissue loss (Kappa = 0.63), but it was lower for chronic ischaemia without tissue loss (Kappa = 0.32) and acute limb ischaemia (Kappa = 0.15). Agreement on comorbidities was mixed; excellent for diabetes (Kappa = 0.82), moderate for chronic lung disease (Kappa = 0.56), chronic kidney disease (Kappa = 0.56), and ischaemic heart disease (Kappa = 0.45) and fair for chronic heart failure (Kappa = 0.35). The diagnostic ICD-10 codes currently used in HES cannot accurately differentiate between stages of PAD. Therefore, studies using HES to examine patterns of care and outcomes for patients with PAD are likely to suffer from misclassification bias. Adopting an extended ICD-10 system or the ICD-11 version released to the World Health Organisation member states in 2022, may overcome this problem. Healthcare Quality Improvement Partnership (HQIP).


Significance of sleep stability using cardiopulmonary coupling in sleep disordered breathing.
The aim of this study was to assess the sleep quality and sleep stability according to the severity of obstructive sleep apnea (OSA) by using questionnaires and cardiopulmonary coupling (CPC) analysis. Two hundred and twenty-one adults were evaluated using subjective sleep questionnaires, CPC parameters, and respiratory parameters measured during full-night polysomnography. We measured the differences in the CPC parameters of each OSA group and the correlation between the apnea-hypopnea index (AHI) and CPC parameters. AHI and CPC parameters were not associated with sleep questionnaires. AHI is negatively correlated with high frequency coupling (HFC, r = -0.725, P < 0.001) and very low frequency coupling (VLFC, r = -0.475, P < 0.001), but it is positively correlated with low frequency coupling (LFC, r = 0.786, P < 0.001) and narrow- and broadband-elevated low frequency coupling (e-LFCNB and e-LFCBB ; r = 0.522, P < 0.001 and r = 0.668, P < 0.001, respectively). We also found similar results regarding the correlation between the arousal index and CPC parameters. In addition, there were significant differences in HFC, LFC, VLFC, e-LFCNB , and e-LFCBB (all P < 0.001) between the severe OSA group and all other groups. We found that CPC parameters significantly correlated with AHI. In addition, sleep stability-related parameters differ significantly based on OSA severity, and apneic parameters in the severe OSA group are significantly different from those in the other groups. 4 Laryngoscope, 130: 2069-2075, 2020.


Aestival dormancy in the cabbage moth Mamestra brassicae L. (Lepidoptera: Noctuidae) : 2. Geographical variation in two traits: Day length thresholds triggering aestival dormancy and duration of aestival dormancy.
In a geographically wide distribution the life cycles of different populations of the cabbage moth Mamestra brossicae are adapted to a remarkable diversity of climatic conditions. This is undoubtedly a proof of its success in adaptation. Some populations living in regions characterized by a drought period interrupting the growth season are capable of distinguishing between one critical day length signalling the onset of the drought period and another signalling the end of the growth season. This study, therefore, is primarily concerned with the geographical patterns in the variability of the adaptional responses of populations exposed to environmental conditions requiring different strategies and tactics in, synchronizing individual, life cycles. It is also a contribution to our understanding of evolutionary mechanisms maintaining median responses to photoperiodically inductive day lengths in geographically different populations. The populations investigated originated from regions differing in predictability of the incidence, onset and duration of a drought period: Freiburg (48.0°N, Southern Germany), Avignon (44.0°N, Southern France), and Argelès (42.5°N, Southern France). Geographical variation with respect to both onset and duration of a drought period consequently results in clinal variation of the variability of innate day length thresholds triggering aestival dormancy and of innate duration of aestivation. In this paper we considered the influence of geographically changing temperatures on aestival dormancy induction. Even in southern populations of M. brassicae a temperature dependent "switch off"-mechanism exists which prevents aestival dormancy under certain environmental conditions. The effective temperatures vary geographically, too. What the geographical patterns in adaptive responses really are, is discussed.


Evidence for recurrent inhibition of reciprocal inhibition from soleus to tibialis anterior in man.
Reciprocal inhibition between ankle flexors and extensors has been the subject of numerous studies in Man. They have demonstrated that this reciprocal inhibition is in all likelihood caused by a disynaptic pathway at least partly fed by Ia afferents. It is thus generally agreed that this reciprocally organized inhibition between ankle flexors and extensors in Man is similar to the reciprocal Ia inhibition described in the cat. This conclusion has, however, been challenged, when Jankowska and McCrea described in the cat a non-reciprocal group I inhibition involving interneurones co-excited by Ia and Ib afferents and mediating inhibition to both antagonistic and non-antagonistic motoneurones. The only way to distinguish between reciprocal Ia inhibition and non-reciprocal group I inhibition is to test if the inhibition is blocked by recurrent inhibition, since only Ia interneurones are inhibited by recurrent inhibition. In the present study, reciprocal inhibition from soleus to tibialis anterior was thus investigated following activation of soleus-coupled Renshaw cells in normal human subjects. It was found that reciprocal inhibition induced in tibialis anterior motoneurones by the activation of soleus group I afferents is deeply depressed by activation of soleus-coupled Renshaw cells. This finding provides the missing data to identify disynaptic inhibition between antagonistic ankle muscles as a reciprocal Ia inhibition.


Feeding the low-birth weight infant: V. Effects of taurine, cholesterol, and human milk on bile acid kinetics.
This study was conducted to compare the influence of diet on the physiologic changes in bile acid kinetics, intraluminal bile acid concentrations, conjugation patterns, and nutrient lipid absorption, which occur postnatally. Preterm infants, 31-35 wk gestation, were fed one of four diets: (a) human milk pasteurized at 62 degrees C for 30 min, 55% from a pooled source, 35% from the infant's own mother, with the remainder (approximately 10%) being fresh human milk; (b) an adapted infant formula (F1); (c) F1 supplemented with taurine, 30 mumol/dl, (F2); and (d) F1 with both taurine, 30 mumol/dl, and cholesterol, 9.6 mg/dl, to a total of 12.7 mg/dl, the levels found in human milk (F3). In all infants, the bile acid pool size increased nearly twofold between 11 and 35 days, irrespective of dietary regimens. Taurine conjugation of bile acids predominated in all infants at 11 days of age and at 35 days in those infants fed human milk or the taurine-supplemented formulas. In taurine-supplemented formulas, the conjugation pattern did not influence bile acid kinetics. However, the bile acid pool and intraluminal bile acid concentrations were significantly greater in infants fed human milk at all ages, suggesting that human milk feeding, per se, uniquely influences intestinal and possibly hepatic function independent of developmental factors.


Drug screening model meets cancer organoid technology.
Tumor organoids inherit the genomic and molecular characteristics of the donor tumor, which not only bridge the gap between genome and phenotype but also circumvent the disadvantages such as genetic information change by using 2D cell lines and the mouse-specific tumor evolution in patient-derived xenograft (PDX). So, cancer organoid has been widely applied to preclinical drug evaluation, biomarker identification, biological research, and individualized therapy. Besides, cancer organoid can be preserved, resuscitated, passed infinitely, and mechanically cultured on a chip for drug screening; it has become one of the partial models for low/high-throughput drug screening in the preclinical trial in vitro. Therefore, this review presents the recent developments of tumor organoids for drug screening, which will introduce from four aspects, including the stability/credibility, types, application, deficiency and prospect of the tumor organoids model for drug screening.


Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology.
Epidemiologic evidence indicates that several markers of exposure to childhood infections are inversely associated with the risk of childhood leukemia and lymphomas. We used the Swedish Family-Cancer Database to assess the effects of number of siblings on the risk of non-Hodgkin's (n = 7,007) and Hodgkin's lymphomas (n = 3,115), leukemias (n = 7,650), and multiple myeloma (n = 1,492) by histopathology. Poisson regression models included terms for age, sex, family history, period, and socioeconomic index. Having four or more siblings compared with none was associated with an excess risk of childhood acute lymphoblastic leukemia [ALL; rate ratio (RR), 2.11; P(trend) = 0.001], acute monocytic leukemia (RR, 2.51; P(trend) = 0.002), and multiple myeloma (RR, 1.34; P(trend) = 0.006). Having three or more older siblings compared with none decreased the risk of acute monocytic leukemia (RR, 0.35; P(trend) = 0.001) and childhood ALL (RR, 0.69; P(trend) = 0.01). The risk of Hodgkin's lymphoma for five or more older siblings compared with none was 0.41 (P(trend) = 0.003). Acute myeloid leukemia, chronic lymphocytic leukemia, and other lymphoproliferative malignancies were not associated with number of siblings. In conclusion, we found an excess risk of childhood ALL and acute monocytic leukemia in large families. However, for ALL, acute monocytic leukemia, and Hodgkin's lymphoma, younger siblings were strongly protected compared with older siblings. The remarkable protective effect of number of older siblings on acute monocytic leukemia is a novel finding of potential interest. Possible interpretations of our findings in the context of a putative infectious etiology are discussed.


Roles of the threonine 407, aspartic acid 417, and threonine 419 residues in P450 2B1 in metabolism.
We have previously observed that the quadruple (S407T-N417D-A419T-K473M) and triple (S407T-N17D-A419T) mutants of the chimeric construct of P450 2B1/2B2 do not undergo mechanism-based inactivation by 17alpha-ethynylestradiol (17EE) and tert-butyl 1-methyl-2-propynyl ether (tBMP). The ability of these mutants to metabolize 17EE, benzphetamine, and testosterone has been investigated. The profile for 17EE metabolism by both mutants was characteristic of both wild-types. The two mutants metabolized testosterone to form androstenedione with no formation of the hydroxy products as was seen with both the wild-types. Benzphetamine metabolism by the mutants showed that both mutants exhibited an increased tendency to catalyze demethylation rather than debenzylation. In the presence of the alternate oxidants cumene hydroperoxide and tert-butyl hydroperoxide, the wild-type 2B1 was not inactivated by 17EE. Metabolism of 17EE by 2B1 supported by these alternate oxidants revealed differences in the metabolites that may be related to the inability of 2B1 to be inactivated under these conditions.


The level of body balance in standing position and handstand in seniors athletes practicing artistic gymnastics.
The aim of the study was to compare the values of selected stability indices registered in the trials in standing with eyes open and without visual control, and in handstand in athletes practicing gymnastics at the highest level of advancement. The study included 20 athletes practicing gymnastics. The research tool was posturograph CQ-Stab 2P. The results obtained in individual trials were compared using Friedman repeated measures analysis of variance by ranks and then subjected to Dunn post-hoc test with Bonferroni adjustment. Statistically significant differences in the values of stability indices recorded in individual samples were found. Exceptions are the results obtained in the trials with eyes open and without visual control with regard to the size of the surface area delineated by the COP (p = 0.173) and the frequency of corrective reactions (p = 0.464), as well as the length of the statokinesiogram path in the mediolateral direction (p = 0.342), mean velocity of COP movement in the mediolateral direction (p = 0.246), maximal amplitude of the COP in the mediolateral direction (p = 0.342) and number of COP displacements in the mediolateral direction (p = 0.246). In seniors, disabling visual control during free standing as well as adopting a handstand position result in deterioration of the stability indices, which is a resultant of the COP displacement in both directions as well as in the anteroposterior direction. Lack of differences in the values of stability indices in the mediolateral direction suggest that in a free standing position, seniors practicing gymnastics control the movement of the center of foot pressure in the mediolateral direction and eye control is not important for the stability of the body in the frontal plane.


Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer.
We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360®, 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review. The median number of alterations and a median maximum mutant allelic fraction (MAF) in MSI-H and non-MSI-H cohorts are compared with Mann-Whitney U-test. Of 6718 patients with breast cancer with ≥1 plasma NGS alteration, 42 (0.63%) have MSI-H. A median number of genomic alterations per sample is 11 in MSI-H vs. 3 in non-MSI-H (Mann-Whitney U-test p < 0.0001) and the median maximum MAF is 16.8% in MSI-H vs. 2.6% in non-MSI-H (Mann-Whitney U-test p < 0.0001). The co-existing genomic landscape is heterogeneous. The median response duration for seven patients receiving immunotherapy is 92 days (range 29-273 days). CfDNA can identify MSI-H in MBC. Research is needed to validate immunotherapy usage in cfDNA-detected MSI-H MBC.


Effect of splenectomy on production of interferon and colony-stimulating factor in Listeria monocytogenes-infected mice.
Splenectomy of mice genetically susceptible to Listeria monocytogenes genetically susceptible mouse strains increased their resistance to L. monocytogenes infection but had no effect on the course of infection in L. monocytogenes-resistant mice. However, splenectomy led to a dramatic decrease in the production of colony-stimulating factor and interferon after L. monocytogenes infection in all mouse strains examined.


Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan micropig and rabbit.
To estimate the feasibility of the subretinal concept of a visual prosthesis, animal models and prototypes, each representing a certain aspect of the final prosthesis, were utilised to test for requirements for such a medical device: (1) the ability to elicit--by electrical stimulation--event-related central activity in the central visual system, and (2) the long-term biocompatibility and biostability of the implant within the subretinal space. (1) In rabbit and Yucatan minipig, cortical evoked potentials were recorded with chronically implanted epidural electrodes during stimulation with light flashes as well as during electrical stimulation in the subretinal space. Voltage pulses ranging from -3 V to +3 V were applied via an acutely implanted electrode array on a wired prototype. (2) For biocompatibility studies a silicon-based micro-photodiode array (MPDA) was used that closely resembled the design and composition of the final prosthesis. Fourteen months after implantation, angiography was performed and the histological findings of the retina in the immediate vicinity of the implant were evaluated. (1) In both rabbit and minipig, subretinal electrical stimulation resulted in evoked cortical potentials that were comparable to visual evoked potentials. The lowest threshold levels for the subretinal stimulation were 0.6 V for rabbits and 2 V for minipigs. (2) Long-term stability of an implanted MPDA and its biocompatibility were proven for a postoperative period of 14 months. Data from animal experiments with certain prototypes of the final prosthesis suggest the feasibility of the concept of a subretinal visual prosthesis: Both requirements were met: (1) the functioning of the subretinal stimulation and (2) the biocompatibility of the MPDA implant.


Lung resection for metastatic sarcoma.
Our experience with lung resection in fifty patients with metastatic sarcoma is presented. Seventeen patients underwent lung resection for solitary lung metastasis and thirty-three had multiple metastases. The overall estimated median survival of the patients was 22.2 months. Shorter tumor doubling time was found to indicate poor prognosis. The tumor-free interval, length of the waiting period, and the number of metastatic lesions removed did not influence the postoperative survival rate. Surgical therapy of solitary as well as multiple metastatic sarcoma of the lung appears to produce acceptable therapeutic results.


Dissemination of successful international clone ST15 and clonal complex 17 among Bulgarian CTX-M-15 producing K. pneumoniae isolates.
A total of 82 extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae and 4 Klebsiella oxytoca isolates were collected in 2014 from four geographical areas in Bulgaria and their multilocus sequence type (MLST) and transferability of the ESBL encoding genes were investigated. The predominant type was CTX-M-15 (87%), followed by CTX-M-3 (9%), SHV-12 or SHV-2 (2%) and CTX-M-14 (1%). The CTX-M-15 producers belonged to ST15 (34.1%) and to a lesser extent to CC17 (ST16, ST17, ST336). The CTX-M-15 transconjugants showed a presence of R, A/C2 and F replicons. The CTX-M-3 producers were assigned to ST29, ST70, ST432, ST542 and ST15 types and the transconjugants carried M2 replicons. To the best of our knowledge, this is the first report that fully describes the MLST types among Bulgarian ESBL producing K. pneumoniae and the first report of the detection of IncR plasmid replicon type in our country.


HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 allele frequencies of North Tanzanian Maasai.
Locus-specific amplicon sequencing was used to HLA type 336 participants of Maasai ethnicity at the HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci. Participants were recruited from three study villages in North Tanzania, for the purpose of investigating risk factors for trachomatous scarring in children. Other than HLA-A, all loci significantly deviated from Hardy-Weinberg equilibrium, possibly due to high relatedness between individuals: 238 individuals shared a house with at least one another participant. The most frequent allele for each locus were A*68:02 (14.3 %), B*53:01 (8.4 %), C*06:02 (19.2 %), DRB1*13:02 (17.7 %), DQB1*02:01 (16.9 %) and DPB1*01:01 (15.7 %), while the most common inferred haplotype was A*68:02 ∼ B*18:01 ∼ C*07:04 ∼ DRB1*08:04 ∼ DQB1*04:02 ∼ DPB1*04:01 (1.3 %).


Emergency Embolization of a Ruptured Aneurysm of the Internal Iliac Artery by Direct Ultrasound-Guided Puncture: Report of a Case.
We report the emergency embolization of a ruptured aneurysm of the internal iliac artery in a patient at high surgical risk. Admission computed tomography scan showed that the ostium of the aneurysmal internal iliac artery was covered by a covered stent. In this patient, we chose to carry out an embolization of the aneurysm and its efferent arteries by direct puncture of the aneurysmal sac using an antero-external abdominal approach under ultrasound guidance. Short-term results were favorable and we consider that this technique is one of the therapeutic options to discuss in such situation.


The relationship between nurses' stress and nurse staffing factors in a hospital setting.
The present study objective was to examine the relationships between nurses' stress and nurse staffing in a hospital setting. Nurses have many job-related stressors. There is a lack of research exploring the relationship between job stressors to staffing and day of week worked. The sample consisted of registered nurses (RNs) (N = 197) providing direct patient care. Data were collected via electronic software. Variables included demographic information, work setting information, Perceived Stress Scale (PSS) scores and Nursing Stress Scale (NSS) scores. Data analysis included descriptive statistics, correlations and analysis of variance. Among respondents, a positive correlation (r = 0.363, P 0.05) was found between the NSS and PSS and between age and patient work load (i.e. number of patients the nurse cared for) (r = 0.218, P < 0.05). A negative correlation (r = -0.142, P < 0.05) existed between NSS and respondents' age. Analysis of variance showed that younger nurses had more nursing stress than older nurses (F(1,195) = 4.283, P < 0.05). Age, patient work load and day of the week worked are important factors affecting nurses' stress levels. IMPLICATIONS FOR NURSING MANAGEMEN: Nurse managers should consider scheduling as a potential stressor for nurses.


Environmental controls on the seasonality of a drought deciduous shrub, Diplacus aurantiacus and its predator, the checkerspot butterfly, Euphydryas chalcedona.
Diplacus aurantiacus produces a full canopy of leaves during the rainy winter and spring. As the drought begins in summer, all but the terminal leaves are lost. The leaves present during the growth period have a comparatively low specific weight and a high content of water, protein, and non-structural carbohydrate on a weight basis. Leaves of this type have a high carbon-gain per unit dry matter investment.The larvae of Euphydryas chalcedona utilize Diplacus as their principal food source. Following the first winter rains, the shrub starts to grow and the larvae of Euphydryas break diapause and begin actively feeding. Adults are produced which lay eggs that hatch into prediapause larvae. During the end of the growth period of the shrub, as the quality and quantity of Diplacus leaves decline, the prediapause larvae have a brief period of active feeding and growth and then enter diapause. Diplacus produces a leaf surface resin which inhibits the growth of Euphydryas larvae. It is present in the highest amounts on those few leaves that remain on the shrub during the drought period.The type and pattern of herbivore defense in Diplacus fits the model described for "apparent" plants.


A physical therapy decision-making tool for stratifying persons with Parkinson's disease into community exercise classes.
Aim: Physical therapy and exercise are considered essential components in the management of Parkinson's disease (PD). Using our retrospective data and years of experience in assigning persons with PD to multilevel group classes we propose a two-part physical therapy decision-making tool consisting of participant and exercise program considerations. Methods: Retrospective medical record review and therapist consensus identified evaluation considerations determined to aide clinical decision making. The ability of these variables (i.e., demographics, clinical characteristics, clinical measures cut-offs) to predict the class assignment decision of PD-specialized physical therapists was evaluated using discriminant function analysis. Results: Therapist-assigned groups differed significantly on all clinical measures (p < 0.001) which provided the categorical data required for discriminant analysis. Using all variables, the discriminant function analysis predicted class assignment of the therapists with 79% agreement. Conclusion: This proposed tool provides a framework that may guide the process for increasing access to multilevel group classes.


Descriptive epidemiology of idiopathic dilated cardiomyopathy in Washington County, Maryland, 1975-1991.
Estimates of the incidence of idiopathic dilated cardiomyopathy (IDC) were obtained by identifying cases from Washington County, Maryland who were hospitalized at local and regional hospitals over a recent 17 year period. All of the verified cases had evidence of ventricular dilatation and hypokinesis, with a left ventricular ejection fraction of less than 40%. A total of 26 cases were hospitalized over the period 1975-1991. The average age of the cases at the time of diagnosis was 55.5 years (range 22-80 years of age). About 58% of the subjects were males. A marked increase in newly diagnosed cases of IDC occurred in this population in recent years; 38% of the cases (10 of 26) were newly diagnosed during 1991 alone. Over the period 1975-1991, the average annual incidence rate of hospitalized cases was 1.6 per 100,000 among men and 1.2 per 100,000 among women. During the last 7 years of the case ascertainment period (1985-1991), the average annual incidence rate was 3.5 per 100,000 among men and 2.5 per 100,000 among women. These results provide additional evidence that IDC is being increasingly recognized by clinicians, and underscore the need for an improved understanding of the distribution and determinants of this often fatal condition.


Translational pathology, genomics and the development of systemic therapies for acral melanoma.
Acral melanomas arise on the non-hair bearing skin of the palms, soles and in the nail beds. These rare tumors comprise 2-3 % of all melanomas, are not linked to UV-exposure, and represent the most frequent subtype of melanomas in patients of Asian, African and Hispanic origin. Although recent work has revealed candidate molecular events that underlie acral melanoma development, this knowledge is not yet been translated into efficacious local, regional, or systemic therapies. In the current review, we describe the clinical characteristics of acral melanoma and outline the genetic basis of acral melanoma development. Further discussion is given to the current status of systemic therapy for acral melanoma with a focus on ongoing developments in both immunotherapy and targeted therapy for the treatment of advanced disease.


Organic peracids: a structural puzzle for 17O NMR and ab initio chemical shift calculations.
We have applied (17)O NMR spectroscopy to investigate the structure of the organic peracids formed by reaction of acetic acid (AA) or lactic acid (LA) with aqueous hydrogen peroxide (HP), which are used in several "green chemistry" applications. The interpretation of the experimental spectra has been supported by ab initio calculations of the (17)O chemical shifts for several possible species, using a continuum representation of the solvent. The combined use of these tools has also allowed us to discuss the decomposition mechanism of LA/HP solutions. The calculated electric field gradients for water, HP, and CO(2) (a decomposition product of LA) correlate well with the experimental (17)O line widths.


Chromosomal composition of a series of 22 human low-grade gliomas.
G-banded chromosomal analysis was performed on direct and/or in vitro cultures of 22 low-grade gliomas, including nine grade I-II astrocytomas, nine oligodendrogliomas, one mixed tumor oligodendroglioma-astrocytoma, and three ependymomas. Normal diploid stem lines were present in most astrocytomas and oligodendrogliomas, whereas, all three ependymomas displayed polyploid modal numbers. However, secondary cell lines showed the presence of clonal recurrent numerical abnormalities, mainly polysomy 7, monosomy 10 and 22, and loss of the Y chromosome. Clonal structural rearrangements were present with a low incidence; they mainly involved chromosomes #1 and #7. These patterns of chromosome involvement seem to correlate with the scarce previous cytogenetic banding data available from low-grade gliomas. They are also similar to the chromosome alterations found in high-grade gliomas.


Preliminary evidence for homoeostatic mechanism regulating endothelin production in pre-eclampsia.
To find out whether a serum factor in pre-eclamptic women is the cause of the raised serum endothelin concentrations associated with the disorder, the effect of serum from pre-eclamptic women on endothelin production by endothelial cells was compared with that of serum from pregnant and non-pregnant controls. The finding that pre-eclamptic serum suppresses endothelin production suggests that it contains a factor that might be part of a homoeostatic response to raised serum endothelin concentrations in pre-eclampsia.


Three-dimensional culture models for human viral diseases and antiviral drug development.
Researchers are recognizing the limitations of two-dimensional (2D) cell cultures, given the fact that they do not reproduce the morphology and biochemical features that the cells possess in the original tissue. As an alternative, the three-dimensional (3D) cell culture approach offers researchers the possibility to study cell growth and differentiation under conditions that more closely resemble the in vivo situation with regard to cell shape and cellular environment. Currently, 3D culture models are being employed in many areas of biomedical research because they offer a more realistic milieu than 2D cultures. The era of 2D culture techniques is moving towards a new epoch of culture systems in 3D. The present review is focused on topics of research on 3D cell cultures in virology and their use in antiviral drug development.


Log odds of positive lymph nodes as a novel prognostic indicator in NSCLC staging.
The paper aimed to compare the efficacy of log odds (LODDS) compared to a classification based on the distribution of involved lymph nodes (pN) and lymph node ratio (LNR). Material was collected retrospectively from an online survey-based database of the Polish Lung Cancer Group and included a group of 17,369 patients who received radical surgical treatment (R0) due to lung cancer. In the whole group the median survival for N0, N1 and N2 was 76.1, 41.7 and 24.2 months, respectively. The median survival for individual LODDS categories (-6,-4], (-4,-3], (-3,-2], (-2,-1], (-1,0], (0,1] and (1,2] was 76.5, 76.3, 71.7, 45.4, 25.0, 19.1 and 17.7 months, respectively. The median survival for LNR in individual categories (0), (0,0.25], (0.25,05], (0.5075] and (0.75,1.0] was 75.6, 40.3, 24.1, 18.8 and 16.4 months, respectively. A multi-variant analysis demonstrated that each LODDS category is an independent prognostic factor: (-4,-3] (HR = 0.982; 95% CI 0.867-1.112; P = 0.775), (-3,-2] (HR = 1.114; 95% CI 0.984-1.262; P = 0.089), (-2,-1] (HR = 1.241; 95% CI 1.080-1.425; P = 0.002), (-1,0] (HR = 1.617; 95% CI 1.385-1.887; P < 0.0001), (0,1] (HR = 1.918; 95% CI 1.579-2.329; P < 0.0001) and (1,2] (HR = 2.016; 95% CI 1.579-2.573; P < 0.0001). Based on LODDS it is possible to discriminate patients with regard to lung cancer stage more effectively compared to pN and LNR classification, and it is also a better classification system.


Implications of anomalous right subclavian artery in the repair of neonatal aortic coarctation.
Spinal cord perfusion is predominantly from the anterior spinal artery, which arises from the vertebral arteries by way of the subclavian arteries. Anomalous origin of the right subclavian artery and coarctation of the aorta is considered to be an increased risk factor for spinal cord damage, possibly because of the minimal collateral circulation during aortic clamping. The aim of this study is to review 5 consecutive cases of neonatal aortic coarctation with ARSA. Five neonates (0.8 to 4.6 kg) underwent operation between July 1999 and December 2000 with resection of the coarctation and end-to-end anastomosis. Both subclavian arteries (n = 5) and left carotid artery (n = 4) were clamped, leaving the right carotid artery as the sole provider of perfusion for the spinal cord. Despite clamping of both subclavian arteries, right radial artery pressure was measurable in 4 of the 5 cases. Aortic cross-clamp times varied from 12 to 26 minutes at a core temperature of 34 degrees to 35 degrees C. There was no operative mortality. None of the neonates developed any major neurologic sequelae. When clamping the two subclavian arteries during coarctation repair, the spinal artery is left with collateral blood flow that can theoretically originate from the carotid arteries through the circle of Willis and retrogradely down the vertebral arteries. The presence of such collateral circulation was documented as recordable blood pressure in the right radial artery during surgical repair.


Disordered eating behaviours in women with Type 2 diabetes mellitus.
The aim of the article is to investigate the relationship between disordered eating, particularly binge eating, and Type 2 diabetes in women. Subjects included 215 women with Type 2 diabetes (mean age: 58.9 years, mean body mass index (BMI)=33.5 kg/m(2)). Measurements included a structured clinical interview for disordered eating (Eating Disorder Examination, EDE), self-report measures of psychological functioning, glycosylated haemoglobin A1c, BMI. A total of 20.9% of women was binge eating regularly. Binge eating was associated with poorer well being, earlier age of diagnosis, poorer self-efficacy for diet and exercise self-management, and higher BMI. Binge eating frequency predicted blood glucose control after controlling for BMI and exercise level. A history of binge eating independently predicted age of diagnosis of diabetes. Binge eating is relatively common in women with Type 2 diabetes. The relationship between binge eating severity and diabetic control is not explained by overweight. Binge eating may be an independent risk factor for Type 2 diabetes.


[Principles of classification and nomenclature in families with striking social peculiarities shown by an example of the district of Osterburg (author's transl)].
The necessity of an uniform characterization for the so called "families with social perculiarities" is explained. Criterias and designations for this purpose are proposed and used in a survey in the district of Osterburg. It is shown, that social risks concentrate in villages. They increase with a rising number of children, especially in families with 5 and more children, and that the social burden of numerous children is "infectious" in respect of peculiarities. Alcoholism is the most negative of them. The most important tasks are the care of potators and of families with childbirth intervals of less than two years.


Effects of light and dark environments on macaque and human fixational eye movements.
Eye position of two macaques and two humans was recorded while they detected the unpredictable dimming of a fixation spot in a dark or a light environment. Fixational saccades often had complex waveforms that resulted from clustering of two or more saccadic displacements with no intervening drift periods. In the dark, all subjects had low frequencies of saccade clusters (0.15-0.61/sec). Three of the subjects increased the frequency of saccade clusters and decreased the magnitude of the displacements when the task was performed in the normally lighted laboratory. The higher saccade frequencies in the light did not automatically result in greater dispersion of eye position. One of the humans, who had the lowest saccade frequency, was relatively unaffected by the stimulus conditions. The change in stimulus conditions had a more pronounced effect on the fixational eye movements of the macaques than the humans. In the dark, the macaques made saccades mostly down and nasal, but in the light the saccadic displacements occurred over a wider range of angular directions. Mean eye position was higher in the dark than in the light. The humans altered the direction of their saccadic displacements very little and did not change their mean eye position when they switched from a dark to a lighted environment. The influence of a lighted environment is interpreted as an interaction between foveolar and peripheral retinal inputs. The results suggest that fixational saccades may have more than one role, perhaps including stimulation of pathways originating in the peripheral retina. These peripheral field inputs have a stronger effect on the fixational control system of macaques than of humans.


Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia: A Longitudinal Study of Implant and Other Related Risk Factors.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer that has been linked to the use of textured devices. The recent increase in number and frequency of cases has led to worldwide regulatory action. The authors aimed to longitudinally study BIA-ALCL in Australia since the index case was first reported in 2007. Confirmed historical cases were collected and then prospectively analyzed from October 2015 to May 2019. Clinical and implant exposure data were determined and compared with company sales data for 4 devices to generate implant-specific risk. A total 104 cases of BIA-ALCL were diagnosed in Australia with exposure to 149 unique breast implants. The mean age of patients was 48.2 years (range, 22.4-78.5 years). They had an average time from implantation to diagnosis of 6.8 years. A total 51.7% of implants utilized in this cohort were Allergan Biocell devices. The indication for implant usage was for primary cosmetic augmentation in 70%, post-breast cancer reconstruction in 23%, and following weight loss/pregnancy in 7%. The majority of women presented with early (stage 1) disease (87.5%). The risk for developing BIA-ALCL ranged from 1 in 1947 sales (95% confidence interval = 1199-3406) for Silimed Polyurethane devices to 1 in 36,730 (95% confidence interval = 12,568-178,107) for Siltex imprinted textured devices. Implants with higher surface area/texture seem to be more associated with BIA-ALCL in Australia. Recent regulatory action to suspend, cancel, or recall some of these higher risk devices is supported by these findings.


Different patterns of second-line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic): A multinational observational study.
The understanding of second-line use of glucose-lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Our aim was to describe second-line GLD treatment patterns in four Nordic countries. All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second-line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second-line drug. A rapid uptake of newer GLDs (GLP-1RA, DPP-4i and SGLT-2i) over the 10-year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second-line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7-fold greater in Sweden compared to Finland (49% vs 7%), and 1.6-fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively). Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second-line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.


Principles of screening applied to psychiatric disorders.
The morbidity and mortality caused by psychiatric illness is a significant public health problem. The use of a psychiatric screening questionnaire has been one strategy to improve the recognition and treatment of psychiatric disorders in general medical settings. This paper discusses how well psychiatric screening procedures fulfill criteria outlined by the World Health Organization for evaluating the utility of general medical screening efforts. Current research on the utility of screening for psychiatric disorders is reviewed, and the lack of data on the treatment of psychiatric disorders is identified in the general medical sector is emphasized. The randomized clinical trial is offered as the best method to test the efficacy of screening by eliminating various biases outlined in the paper. Quantitative concepts such as positive predictive value and receiver operator characteristic analysis are discussed. The need for more research on the efficacy of early treatment of psychiatric disorders is emphasized.


A systematic review of the measurement properties of self-care scales in nurses.
Self-care is a necessary measure against occupational injuries of nurses and improves nursing performance at the bedside. Nurses have different scales to measure self-care, and researchers are confused about choosing valid and reliable scales. This systematic review aimed to evaluate the measurement properties of self-care scales in nurses to identify the best available scales. Four databases (PubMed, Web of Science, SCOPUS, and ProQuest) were systematically searched, with no date limiters, until 9 Jun 2023. A manual search was performed with Google Scholar and the reference list of articles to complete the search. Studies aiming to develop or determine the measurement properties of self-care in nurses were included. Based on Consensus-Based Standards for the Selection of Health Measurement Instruments, the methodological quality of the studies was determined, and the result of each study on a measurement property was rated (sufficient, insufficient, or indeterminate). The quality of the evidence was graded using a modified Grading of Recommendations Assessment, Development, and Evaluation approach (high, moderate, low, or very low). These processes were used to make recommendations and identify the best scale to assess self-care in nurses. Out of 8601 articles, six articles with five different scales were included. Only internal consistency was reported across all scales. Criterion validity, measurement error, responsiveness, feasibility, and interpretability, were not reported in any of them. Content validity was reported only in two studies with inconsistent results and low-quality evidence. None of the scales had methodological quality with a rating of very good and sufficient high-quality evidence for all measurement properties. None of the scales is strongly recommended to measure self-care in nurses. Only the Professional self-care scale is temporarily recommended until their quality is assessed in future studies. Considering that the content of the examined scales does not meet all the professional self-care needs of nurses, designing a valid, reliable, and specialized scale for nurses is needed.


Genomic organization and chromosome localization of the newly identified human heparanase gene.
Heparanase (HPSE), which we have recently isolated, is an endo-beta-D-glucuronidase capable of cleaving heparan sulfate and has been implicated in inflammation and tumor angiogenesis and metastasis. In this report, the genomic organization and chromosome localization of the human heparanase gene is described. Polymerase chain reaction, subcloning and DNA sequencing analysis of a bacterial artificial chromosome (BAC) clone revealed that the 3.7 kb human heparanase cDNA is spread over about 50 kb and contains 14 exons and 13 introns. The heparanase gene is expressed as two mRNA species containing the same open reading frame, HPSE 1a (5 kb) (GenBank Data Library under accession number: AF155510); and HPSE 1b (1.7 kb) (GenBank Data Library under accession number: AF144325), generated by alternative splicing. The HPSE 1a-form contains all 14 exons, whereas in the HPSE 1b-form the first and fourteenth exons (5'- and 3'-untranslated region) have been spliced out. All splice sites conform to the GT-AG rule, except for the splice donor site of intron 13 (which is GA instead of GT), and the splice acceptor of intron 13 (which is GG instead of AG). Fluorescence in situ hybridization and radiation hybrid mapping suggest that the heparanase gene is located on human chromosome 4q22. This report regarding the structure of the human heparanase gene will aid in understanding the genetic contribution of this gene to normal physiology as well as to disease states. A possible involvement of heparanase in neuronal degeneration is discussed.


Association of IL-6 with PM2.5 Components: Importance of Characterizing Filter-Based PM2.5 Following Extraction.
Filter-based toxicology studies are conducted to establish the biological plausibility of the well-established health impacts associated with fine particulate matter (PM2.5) exposure. Ambient PM2.5 collected on filters is extracted into solution for toxicology applications, but frequently, characterization is nonexistent or only performed on filter-based PM2.5, without consideration of compositional differences that occur during the extraction processes. To date, the impact of making associations to measured components in ambient instead of extracted PM2.5 has not been investigated. Filter-based PM2.5 was collected at locations (n = 5) and detailed characterization of both ambient and extracted PM2.5 was performed. Alveolar macrophages (AMJ2-C11) were exposed (3, 24, and 48 h) to PM2.5 and the pro-inflammatory cytokine interleukin (IL)-6 was measured. IL-6 release differed significantly between PM2.5 collected from different locations; surprisingly, IL-6 release was highest following treatment with PM2.5 from the lowest ambient concentration location. IL-6 was negatively correlated with the sum of ambient metals analyzed, as well as with concentrations of specific constituents which have been previously associated with respiratory health effects. However, positive correlations of IL-6 with extracted concentrations indicated that the negative associations between IL-6 and ambient concentrations do not accurately represent the relationship between inflammation and PM2.5 exposure. Additionally, seven organic compounds had significant associations with IL-6 release when considering ambient concentrations, but they were not detected in the extracted solution. Basing inflammatory associations on ambient concentrations that are not necessarily representative of in vitro exposures creates misleading results; this study highlights the importance of characterizing extraction solutions to conduct accurate health impact research.


On the activation of calcium-dependent proteolysis in brain neurons of spontaneously hypertensive rats (SHR strain).
Females of spontaneously hypertensive (SHR strain) and normotensive rats (WKY strain and Wistar) received drinking water with normal (80 mg/liter) or reduced concentration of Ca(2+)(8 mg/liter). Activity of calcium-dependent calpain protease in neurons did not differ in 18-day-old rat pups born and suckled by these animals. Our results are consistent with published data on normal metabolism of SHR rats up to the age of 30 days.


Apoptosis induced by cold shock in vitro is dependent on cell growth phase.
Chinese hamster V79 fibroblast cells were exposed to brief periods of cold but non-freezing temperatures at different points on the population growth curve. Upon rewarming, cells at the transition from logarithmic to stationary growth exhibited apoptosis (programmed cell death). Cells in other stages of growth, or after reentry into logarithmic growth by refeeding, did not exhibit apoptosis. Apoptosis was expressed by marked cytoplasmic blebbing, by a characteristic non-random fragmentation of DNA into nucleosomal-sized pieces, and by loss of colony-forming ability. The data suggest that cold shock served as a stimulus for susceptible cells to undergo apoptosis. Thus, the experiments describe a new in vitro system for studying the mechanisms of apoptosis.


Acute mushroom poisoning of Amanita pseudosychnopyramis: A case report from Fujian, China with exact species identification and descriptive study.
Mushroom poisoning is a deeply concerning food safety problem that affects the public in China every year. Although there are statistics on the number of poisonings and incidents, there is a lack of data on the types of toxic mushrooms, clinical manifestations and toxins. A case of wild mushroom poisoning occurred in Xiamen. Descriptive epidemiological investigation, toxins detection, and morphological and phylogenetic identification were immediately performed. The patients exhibited typical neurotoxic symptoms after consuming wild mushrooms, including chills, vertigo, drowsiness, salivation and coma. The average incubation period was 30 min. Treatments that were adopted included fluid infusion, gastric lavage, catharsis, and liver protection treatment. All patients recovered within 10 days. The species was identified as Amanita pseudosychnopyramis, and its contents of muscarine, muscimol and ibotenic acid were 170.3 ± 5.9 mg/kg, 835.4 ± 43.1 mg/kg and 637.9 ± 54.8 mg/kg in dry weight, respectively, as detected by ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). To our knowledge, this is the first report of Amanita pseudosychnopyramis poisoning worldwide.


Streamlined sample preparation procedure for determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry.
A rapid, sensitive, and specific method was developed for the determination of perchlorate anion in foods. The foods included high moisture fruits and vegetables, low moisture foods (e.g. wheat flour and corn meal), and infant foods. Improvements to existing procedures were made in sample preparation that reduced sample test portion size from 100 to 5 or 10 g, extraction solvent volume from 150 to 20-40 ml, and replaced blending extraction-vacuum filtration and their associated large glassware with a simple shakeout-centrifugation in a small conical tube. Procedures common to all matrices involved: extraction, centrifugation, graphitized carbon solid phase extraction (SPE) cleanup, and ion chromatography-tandem mass spectrometry (IC-MS/MS) analysis. A Waters IC-Pak Anion HR column (4.6 mm x 75 mm) was eluted with 100mM ammonium acetate in 50:50 (v/v) acetonitrile/water mobile phase at a rate of 0.35 ml/min. A triple stage quadrupole mass spectrometer, equipped with electrospray ionization (ESI) in the negative ion mode, was used to detect perchlorate anion. An 18O4-labeled perchlorate anion internal standard was used to correct for any matrix effects. The method limit of quantitation (LOQ) was: 1.0 microg/kg in fruits, vegetables, and infant foods; 3.0 microg/kg in dry products. Fortified test portions gave 80-120% recoveries. Determination of incurred perchlorate anion residues agreed well with results for comparable commodities or products analyzed by published methods.


Regulation of the C-X-C chemokine, mob-1, gene expression in primary rat hepatocytes.
The chemokine, mob-1, is involved in inflammatory and immune responses and may be an important mediator of the inflammatory response in the liver. Here, we investigated the upstream signal pathways that could be involved in the regulation of mob-1 expression. We have found that in primary rat hepatocytes the isolation and subsequent culture of these cells induced mob-1 expression. A similar induction of mob-1 mRNA was observed when the hepatocytes were stimulated with interferon-gamma (IFN-gamma). When hepatocytes were stimulated with IFN-gamma or cytokine mixture (IFN-gamma, interleukin-1beta and tumour necrosis factor-alpha), c-Jun N-terminal kinase (JNK), p38 and extracellular-regulated kinase (ERK) were phosphorylated, suggesting an involvement of the mitogen-activated protein kinases (MAPK) in the induction of mob-1 expression. The p38 kinase inhibitor, SB 203580, and the NF-kappaB inhibitor, MG-132, inhibited the induction of mob-1 mRNA and the effects were not additive. These results demonstrate that in primary rat hepatocytes the transient induction of mob-1 expression was regulated by p38 kinase and NF-kappaB through a common regulatory pathway.


Allergenic characterization of Acarus siro and Tyrophagus putrescentiae and their crossreactivity with Lepidoglyphus destructor and Dermatophagoides pteronyssinus.
Allergenic components in extracts of Acarus siro and Tyrophagus putrescentiae were identified by sodium dodecyl sulphate-polyacrylamide (SDS-PAGE) and immunoblotting. Five and four allergenic components, respectively, were visualized with sera from farmers sensitized to storage mites. The highest frequency of IgE-binding was to a 15 kDa component of A. siro (7/9 sera) and a 16 kDa component of T. putrescentiae (23/29 sera). The allergenic crossreactivity of A. siro and T. putrescentiae with Lepidoglyphus destructor and Dermatophagoides pteronyssinus was studied with an immunoblotting inhibition technique. Crossreactivity between D. pteronyssinus on the one hand and A. siro and T. putrescentiae on the other, was shown, as the IgE reactivity to a 25 kDa component of D. pteronyssinus was inhibited to the same degree by extracts of A. siro, T. putrescentiae and D. pteronyssinus. However, D. pteronyssinus was a poor inhibitor of the allergenic components of A. siro and T. putrescentiae. Strong cross-reactivity was also shown between L. destructor and the allergenic components of A. siro and T. putrescentiae, while the latter mite species only to a very low degree inhibited the allergenic components of L. destructor.


Risk factors for isolation of carbapenem-resistant Enterobacterales from normally sterile sites and urine.
Invasive infections caused by carbapenem-resistant Enterobacterales (CRE) are of significant concern in health care settings. We assessed risk factors for a positive CRE culture from a sterile site (invasive infection) compared to isolation from urine in a large patient cohort in Atlanta from August 2011 to December 2015. CRE cases required isolation, from urine or a normally-sterile site, of E. coli, Klebsiella spp., or Enterobacter spp. that were carbapenem-nonsusceptible (excluding ertapenem) and resistant to all third-generation cephalosporins tested. Risk factors were compared between patients with invasive and urinary infections using multivariable logistic regression. A total of 576 patients had at least 1 incident case of CRE, with 91 (16%) having an invasive infection. In multivariable analysis, the presence of a central venous catheter (OR 3.58; 95% CI: 2.06-6.23) or other indwelling device (OR 2.34; 95% CI: 1.35-4.06), and recent surgery within the last year (OR 1.81; 95% CI: 1.08-3.05) were associated with invasive infection when compared to urinary infection. Health care exposures and devices were associated with invasive infections in patients with CRE, suggesting that targeting indwelling catheters, including preventing unwarranted insertion or encouraging rapid removal, may be a potential infection control intervention. Future infection prevention efforts to decrease CRE cases in health care settings should focus on minimizing unnecessary devices.


Is distance from equilibrium a good indicator for a reaction's flux control?
By analysing a large set of models obtained from the JWS Online and Biomodels databases, we tested to what extent the disequilibrium ratio can be used as an estimator for the flux control of a reaction, a discussion point that was already raised by Kacser and Burns, and Heinrich and Rapoport in their seminal MCA manuscripts. Whereas no functional relation was observed, the disequilibrium ratio can be used as an estimator for the maximal flux control of a reaction step. We extended the original analysis of the relationship by incorporating the overall pathway disequilibrium ratio in the expression, which made it possible to make explicit expressions for flux control coefficients.


Introducing Materials Science: Experimenting with Magnetic Nanomaterials in the Undergraduate Chemistry Laboratory.
Materials science research has expanded significantly in recent years; a multidisciplinary field, home to an ever-growing number of chemists. However, our general chemistry degree courses have not changed to reflect the rise in interest in this topic. In this paper, we propose a laboratory experiment for the undergraduate chemistry practical course, which may serve as a hands-on introduction to this field. The experiment involves the synthesis and characterization of magnetic materials via commonly employed techniques in materials science. Students begin by producing three metal ferrite spinels using a sol-gel combustion synthesis. They must then characterize the differing magnetic properties across their three samples using a magnetic susceptibility balance. In the second part of the experiment, students must create a ferrofluid via coprecipitation, from which they may observe the phenomenon of "spiking" in response to an external magnet. Additional data such as X-ray diffraction (XRD) patterns and transmission electron microscopy (TEM) images corresponding to these materials are also provided, and students are tasked with the interpretation of these data in their writeup report. Upon completion, students should gain a new-found understanding of materials science and its fundamental overlap with chemistry.


Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate.
Duck hepatitis B virus, a DNA virus closely related to human hepatitis B virus, was studied in infected duck liver. Subviral particles resembling the viral nucleocapsid cores were isolated from persistently infected liver and shown to have a DNA polymerase activity that utilizes an endogenous template and synthesizes both plus- and minus-strand viral DNA. Synthesis of the viral minus-strand DNA utilized an RNA template that was degraded as it was copied. Viral plus-strand synthesis occurred on the completed minus-strand DNA. A pathway for the replication of the DNA genome of hepatitis B-like viruses by reverse transcription of an RNA intermediate is proposed.


Glucose transporter 3 (GLUT3) protein is present in human myocardium.
Glucose and fructose enter mammalian cells via facilitated diffusion, a process regulated by five glucose transporter isoforms (GLUT1-5) at the plasma membrane. The tissue-specific pattern of GLUT isoform expression likely reflects differing needs for glucose transport by various tissues. Myocytes must respond expeditiously to increased metabolic demand. A basal isoform, GLUT1, and the insulin-regulatable glucose transporter, GLUT4, have been demonstrated in human myocytes. GLUT3 has a high affinity for glucose, but its presence in human myocardium has not been clearly established. The purpose of this study was to determine whether GLUT3 protein is present in human cardiac myocytes. We examined rapidly frozen myocardial tissue from the explanted heart of seven patients undergoing cardiac transplantation, from the heart of a young, previously healthy male organ donor, from the heart of a 67-year-old woman without known cardiac disease who had a fatal stroke, and from the heart of six human fetuses. GLUT3 protein was detected by immunoblots and localized by light and electron microscopy immunohistochemistry. The presence of GLUT3 protein was verified in myocardial tissue by both immunoblots and immunohistochemistry. Light and electron microscopy confirmed that GLUT3 was in cardiac myocytes. GLUT3 was also demonstrated as a 48 kDa protein in fetal myocardium, which was present at 10 weeks, increased at 15 weeks, then decreased at 20 weeks of gestation. GLUT3 is present in human adult and fetal myocardium. Human myocardial GLUT3 regulation and its role in myocardial glucose uptake remain to be elucidated.


Fungal prostatitis due to endemic mycoses and Cryptococcus: A multicenter case series.
Fungal prostatitis is exceedingly rare with mostly case reports. Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.


Spatial aspects of the supply-demand gap and its change in childcare services in Naha City, Japan.
Given the recent increase in the number of working mothers, Japanese cities face a shortage of childcare services. In response to this problem, Japan's central government has attempted to expand childcare facilities by implementing a comprehensive support system for children and child-rearing. However, a geographical approach is needed to evaluate the impact of the new system from the viewpoint of territorial justice in order to reconcile efficiency and equity in public service provision. Therefore, this study examines the spatial aspects of the supply-demand gap in childcare services following the implementation of the new system. The area studied was Naha City in Okinawa Prefecture, where the number of children awaiting enrollment in licensed childcare centers is exceptionally large. Since 2015, the city authorities have provided financial assistance to transform unlicensed childcare facilities into licensed ones to increase the provision of childcare services. As a result, the number of children awaiting enrollment in licensed childcare centers has reduced. Nevertheless, a spatial analysis of the supply-demand gap in childcare services using a geographic information system proves that a regional imbalance in childcare provision still exists in Naha City.


Effects of a biomimetic analog-based experimental bonding system on caries-affected and sound dentin.
This study compared the ultrastructure, chemical composition, and proteases activity (PA) of sound (SD) and caries-affected dentin (CAD) in the dentin hybrid layer after using an experimental bonding system containing pyromellitic dianhydride glycerol methacrylate and biomimetic analogs. The bonding system used a three step and a total-etch procedure. Polyacrylic acid (5%) and sodium trimetaphosphate (5%) were added to the primer and monocalcium phosphate monohydrate (9%), beta-tricalcium phosphate (10.5%), and calcium hydroxide (0.5%) were added to the adhesive. Transmission electron microscopy (TEM) was used to evaluate the resultant structure, particularly the adhesive-dentin and the demineralized-SD interfaces. The chemical composition was evaluated through energy-dispersive X-ray spectroscopy (EDS) and selected area electron diffraction (SAED). The PA was measured with the Coomassie Blue-G250 coloring test, and the PA data were analyzed by ANOVA. EDS identified the presence of isolated calcium phosphate nanoparticles in the demineralized region; however, the SAED analysis did not show any evidences of hydroxyapatite (HA) neoformation in SD and CAD. The biomimetic analog-based adhesive system inhibited the activities of dentin proteases immediately after treatment. Additionally, the proteolytic activity on the affected dentin resembled that of the SD. In conclusion, no HA formed in the demineralized SD and CAD although there were calcium and phosphate deposits. The experimental adhesive system inhibited dentin proteases. The present study uses a new approach to investigate the hybrid layer behavior in dentin. The experimental adhesive system was synthesized and used on sound and affected-caries dentin as the substrate to reproduce real clinical conditions.


Kraft lignin grafted with isopentenol polyoxyethylene ether and the dispersion performance.
In order to develop a biomass-based superplasticizer, kraft lignin (KL) was grafted with isopentenol polyoxyethylene ether (TPEG) to prepare a novel macromonomer (KL-TPEG). It was shown that the retention ratio of the aliphatic CC bond increased from 81.07% to 90.20% with the increase of m(TPEG)/m(KL). When the grafting ratio was increased, the average number of TPEG grafted on one KL molecule was approximately 1.4, 3.1, 4.6, 6.2 and 7.6. The star-like structure was also confirmed by FT-IR, 1H NMR and GPC. KL-TPEG had favorable surface activity and dispersion stability on the cement particles. It was illustrated that the shear stress and shear viscosity of the cement slurries with KL-TPEG were significantly less than that of blank slurry. The dispersion-retention ability of KL-TPEG on the slurry was also gradually enhanced with the increase of the grafting ratio of TPEG. It was seldom reported on the biomass-based TPEG. Through modified with KL, the rheology behavior and the dispersion-retention ability of TPEG was greatly improved, and the cost of TPEG was also reduced, thus this study not only promoted the development of biomass-based macromonomer, but also helped for the high value utilization of lignin.


Cocaine effects during D-amphetamine maintenance: a human laboratory analysis of safety, tolerability and efficacy.
Agonist replacement therapies are effective for managing substance abuse disorders including nicotine and opioid dependence. The results of preclinical laboratory studies and clinical trials indicate that agonist replacements like D-amphetamine may be a viable option for managing cocaine dependence. This experiment determined the physiological and behavioral effects of cocaine during D-amphetamine maintenance in seven cocaine-dependent participants. We predicted cocaine would be well tolerated during D-amphetamine maintenance. We also predicted D-amphetamine would attenuate the behavioral effects of cocaine. After 3-5 days of D-amphetamine maintenance (0, 15, and 30 mg/day), volunteers were administered ascending doses of cocaine (4, 30, 60 mg, i.n.) within a single session. Cocaine doses were separated by 90 min. Cocaine produced prototypical physiological (e.g., increased heart rate, blood pressure, and body temperature) and subject-rated (e.g., increased ratings of Good Effects) effects. During maintenance on the highest D-amphetamine dose, the heart rate increasing effects of cocaine were larger than observed during placebo maintenance. These effects were not clinically significant and no unexpected or serious adverse events were observed. D-amphetamine attenuated some of the subject-rated effects of cocaine. These results are concordant with those of previous preclinical studies, human laboratory experiments and clinical trials, further suggesting that agonist replacement therapy may be a viable strategy for managing cocaine abuse. Additional research in humans is needed to determine whether D-amphetamine attenuates the effects of cocaine under different experimental conditions (e.g., higher cocaine doses) and behavioral arrangements (e.g., drug self-administration or discrimination).


MHC II - EGFP knock-in mouse model is a suitable tool for systems and quantitative immunology.
Immunology is a rapidly evolving field of research with sophisticated models and methods. However, detailed data on total immune cell counts and population distributions remain surprisingly scarce. Nevertheless, recently established quantitative approaches could help us understand the overall complexity of the immune system. Here, we studied a major histocompatibility complexclass II - enhanced green fluorescent protein knock-in mouse model to precisely identify and manipulate lymphoid structures. By combining flow cytometry with light sheet microscopy, we quantified MHC II+ populations of the small intestine and associated individual mesenteric lymph nodes, with 36.7 × 106 cells in lamina propria, 3.0 × 105 cells in scattered lymphoid tissue and 1.1 × 106 cells in Peyer's patches. In addition to these whole-organ cell counts, we assessed approximately 1 × 106 total villi in the small intestine and 450 scattered lymphoid tissue follicles. By direct noninvasive microscopic observation of a naturally fully translucent mouse organ, the cornea, we quantified 12 ± 4 and 35 ± 7 cells/mm2 Langerhans- and macrophage-like populations, respectively. Ultimately, our findings show that flow cytometry with quantitative imaging data analysis enables us to avoid methodological discrepancies while gaining new insights into the relevance of organ-specific quantitative approaches for immunology.


Quantitative studies of CD8+ T-cell responses during microbial infection.
MHC class I tetramer staining, intracellular cytokine staining and ELISPOT assays have made it possible to quantify CD8(+) T-cell responses precisely during and following viral and bacterial infection. Although these quantitative methods are by now familiar and trusted components of the immunologist's toolbox, their application to models of microbial infection continues to provide surprising insights into mammalian adaptive immunity. In the past year there have been many exciting new findings on CD8(+) T-cell priming, expansion and memory formation in response to microbial infection.


Optimal foraging by predaceous diving beetle larvae on toad tadpoles.
The feeding behavior of predaceous beetle larvae (Dytiscus fasciventris) on American toad (Bufo americanus) tadpoles was investigated in the laboratory. The rate of food extraction from an individual tadpole decreases as the prey item is being depleted. Beetles hand fed single tadpoles were shown to have a significantly longer mean handling time than beetles capturing similar size tadpoles from constant prey densities of 5 or 20 tadpoles/1. Handling times were not correlated with mean intercatch intervals but were found to decrease throughout a 10-tadpole catch sequence at all prey densities. Beetles allocated less time per unit weight to large prey items than to smaller tadpoles. However, the marginal ingestion rate (amount consumed/unit of handling time) did not differ with prey size throughout a 10-tadpole catch sequence. These results support the rate expectation hypothesis (Charnov 1976) as an explanation for time allocation to patches.


Measurement of troponin I 48 h after admission as a tool to rule out impaired left ventricular function in patients with a first myocardial infarction.
Few studies have evaluated cardiac troponin I (cTnI) as a marker for infarct size and left ventricular (LV) dysfunction. Here we investigated the ability of a single-point cTnI, measured with a second-generation assay (Access AccuTnI), to estimate infarct size and assess LV function in patients with a first myocardial infarction (AMI). cTnI measurements were performed 12 and 48 h after admission in 63 consecutive AMI patients. LV function was evaluated by gated single-photon emission computed tomography (SPECT) and infarct size was estimated by CK-MB peak and SPECT myocardial perfusion. LV function and infarct size were evaluated by SPECT before hospital discharge. SPECT was also repeated 3 months later. Significant correlations (p<0.001) were found between cTnI at 12 and 48 h and both the peak CK-MB (r=0.61 and r=0.82, respectively) and the perfusion defect size at SPECT (r=0.55 and r=0.61, respectively). cTnI at 12 and 48 h were inversely related (p<0.001) to LV ejection fraction (LVEF) assessed both early (r=-0.45 and r=-0.57, respectively) and 3 months after AMI (r=-0.51 and r=-0.69, respectively). cTnI >14.8 microg/L at 48 h predicted an LVEF <40% at 3 months with a sensitivity of 100% [95% confidence interval (CI) 73.5-100%], specificity of 65% (CI 49-79%), and a negative predictive value of 100%. Our findings demonstrate that a single cTnI measurement 48 h after admission is useful for ruling out impaired LV function in a routine clinical setting.


Influence of external concentration fluctuations on leukocyte chemotactic orientation.
The quantitative dependence of leukocyte chemotactic orientation on imprecision in the measurement of chemoattractant concentrations from thermal fluctuations is analyzed. First, a mathematical model relating orientation to differences in receptor occupancy across cell dimensions is developed. This is then coupled with an extension of Berg and Purcell's analysis (1) of the precision of attractant concentration measurements by means of receptor occupancy. Our results show that thermal fluctuations in external concentrations can limit the accuracy of orientation, unless the measurement noise is reduced by averaging the measurements over a period of time. Comparison of our model predictions to experimental orientation data suggests that leukocytes do overcome this limitation, and allows estimation of the time-averaging period necessary to do so. For the orientation observed in a visual bridge assay by Zigmond (2) using the attractant peptide FNLLP, we estimate that receptor occupancy measurements for spatial comparison across cell dimensions must be averaged for a few minutes. Otherwise, the fluctuations in the attractant concentration near the cell will be too great to allow the observed degree of orientation. Our analysis also suggests that the ratio of signal-to-signal noise does not adequately characterize orientation accuracy. Accurate orientation can, in some situations, occur when this ratio is substantially less than unity; in other situations, a ratio much greater than unity is required for accurate orientation.