Single-dose intranasal subunit vaccine rapidly clears secondary sepsis in a high-dose pneumonic plague infection.
Yersinia pestis, the causative agent of plague, has killed millions throughout human history. Though public health initiatives have reduced the number of plague cases, it remains endemic in many areas of the world. It also remains a significant threat for use as a biological weapon. Naturally occurring multi-drug antibiotic resistance has been observed in Y. pestis, and resistant strains have been engineered for use as a biological weapon. Vaccines represent our best means of protection against the threat of antibiotic resistant plague. We have developed a vaccine consisting of two Y. pestis virulence factors, LcrV (V) and F1, conjugated to Tobacco Mosaic Virus (TMV), a safe, non-replicating plant virus that can be administered mucosally, providing complete protection against pneumonic plague, the deadliest form of the disease and the one most likely to be seen in a biological attack. A single intranasal (i.n.) dose of TMV-F1 + TMV-V (TMV-F1/V) protected 88% of mice against lethal challenge with 100 LD50 of Y. pestis CO92pgm-, while immunization with rF1 + rV without TMV was not protective. Serum and tissues were collected at various timepoints after challenge to assess bacterial clearance, histopathology, cytokine production, and antibody production. Overall, TMV-F1/V immunized mice showed a significant reduction in histopathology, bacterial burden, and inflammatory cytokine production following challenge compared to rF1 + rV vaccinated and unvaccinated mice. Pneumonic challenge resulted in systemic dissemination of the bacteria in all groups, but only TMV-F1/V immunized mice rapidly cleared bacteria from the spleen and liver. There was a direct correlation between pre-challenge serum F1 titers and recovery in all immunized mice, strongly suggesting a role for antibody in the neutralization and/or opsonization of Y. pestis in this model. Mucosal administration of a single dose of a Y. pestis TMV-based subunit vaccine, without any additional adjuvant, can effectively protect mice from lethal infection.


Hibernoma: a clinical model for exploring the role of brown adipose tissue in the regulation of body weight?
Hibernoma is a rare benign tumor histologically similar to brown adipose tissue. Some studies reported weight loss in patients with this tumor; however, the mechanisms have never been investigated. The purpose of this study is to explore the impact of hibernoma resection on the whole-body metabolism. A 68-year-old woman was examined after a weight loss of 10 kg in 6 months. Body composition, food intake, physical activity, blood levels of thyroid hormones, and lipid profile were assessed before surgery and during 1 year after surgery. The patient's resting energy expenditure (REE) over time was compared to a control group of 18 matched healthy volunteers. Within 1 year after hibernoma resection, the patient gained 15 kg of body weight. This was associated with fat mass gain (+41%), mainly in the abdominal region (+48%). The patient also developed hepatic nonalcoholic steatosis, mild hypertriglyceridemia, and reduced levels of high-density lipoproteins. REE increased during the dynamic phase of weight gain, compared to the presurgery measurement, and returned to baseline after 1 year. Food intake was increased by 37.5% 6 weeks after resection of the hibernoma and returned to baseline values within 6 months. In our study conditions, hibernoma did not alter REE, but weight gain did. Specific physical activities and dietetic follow-ups are suggested for those patients to prevent excess fat mass gain and metabolic disorders after hibernoma resection. More studies should focus on hibernoma mechanisms inducing weight loss.


The Multifunctional Roles of Polyphenols in Plant-Herbivore Interactions.
There is no argument to the fact that insect herbivores cause significant losses to plant productivity in both natural and agricultural ecosystems. To counter this continuous onslaught, plants have evolved a suite of direct and indirect, constitutive and induced, chemical and physical defenses, and secondary metabolites are a key group that facilitates these defenses. Polyphenols-widely distributed in flowering plants-are the major group of such biologically active secondary metabolites. Recent advances in analytical chemistry and metabolomics have provided an opportunity to dig deep into extraction and quantification of plant-based natural products with insecticidal/insect deterrent activity, a potential sustainable pest management strategy. However, we currently lack an updated review of their multifunctional roles in insect-plant interactions, especially focusing on their insect deterrent or antifeedant properties. This review focuses on the role of polyphenols in plant-insect interactions and plant defenses including their structure, induction, regulation, and their anti-feeding and toxicity effects. Details on mechanisms underlying these interactions and localization of these compounds are discussed in the context of insect-plant interactions, current findings, and potential avenues for future research in this area.


Recoding: dynamic reprogramming of translation.
A minority of genes in probably all organisms rely on "recoding" for translation of their mRNAs. In these cases, the rules for decoding are temporarily altered through the action of specific signals built into the mRNA sequences. Three classes are described. 1. Frameshifting at a particular site allows expression of a protein from an mRNA with overlapping open reading frames, often giving two protein products from one mRNA. 2. The meanings of code words are altered: specific stop codons can be redirected to encode selenocysteine, tryptophan, or glutamine. 3. Ribosomes can translate over coding gaps in mRNA. These novel mechanisms expand the repertoire of the genetic code and are at the heart of several regulatory schemes.


Cellular and subcellular distribution of spinophilin, a PP1 regulatory protein that bundles F-actin in dendritic spines.
Spinophilin is an actin binding protein that positions protein phosphatase 1 next to its substrates in dendritic spines. It contains a single PDZ domain and has the biochemical characteristics of a cytoskeletal scaffolding protein. Previous studies suggest that spinophilin is present in most spines, but the concentration of spinophilin varies from brain region to region in a manner that does not simply reflect differences in spine density. Here, we show that spinophilin is enriched in the great majority of dendritic spines in cerebral cortex, caudatoputamen, hippocampal formation, and cerebellum, irrespective of regional differences in spinophilin concentration. In addition, spinophilin is present postsynaptic to asymmetrical contacts on interneuronal dendritic shafts. We further show that, in hippocampus and ventral pallidum, spinophilin is occasionally present in dendritic shafts adjacent to gamma-aminobutyric acid-containing contacts. Thus, the functional role of spinophilin may not be exclusively restricted to excitatory synapses and may be significant at a small fraction of inhibitory contacts. These data also suggest that the concentration of spinophilin per spine is variable and is likely regulated by local physiological factors and/or regional influences.


Klinefelter syndrome associated with goniodysgenesis.
We report a case of a patient with Klinefelter syndrome and glaucoma. A 30-year-old patient with karyotype 47, XXY, presented with a known medical history of glaucoma. Besides reduced fertility, no characteristic physical or behavioral symptoms for Klinefelter syndrome were found on clinical examination. While both eyes were treated with topical intraocular pressure-lowering medications, an increased intraocular pressure, visual field losses, and advanced optic disc damage with a cup-disc ratio of 0.9 were assessed only in the right eye. However, gonioscopy revealed goniodysgenesis in both eyes. Klinefelter syndrome is the most common cause of male hypogonadism with a variety of clinical signs and symptoms. The principal effect is the hypogonadism predisposing to infertility and requiring testosterone replacement therapy. Several other classical features of the syndrome including mental retardation, gynecomastia, and breast cancer are described. However, the association between Klinefelter syndrome and ocular manifestations is rare. : Glaucoma or in fact any other ocular manifestations associated with Klinefelter syndrome are rarely described. Here, we report a case of glaucoma and its treatment combining trabeculotomy and trabeculectomy in a patient with Klinefelter syndrome.


Studying semblances of a true killer: experimental model of human ventricular fibrillation.
It is unknown whether ventricular fibrillation (VF) studied in experimental models represents in vivo human VF. First, we examined closed chest in vivo VF induced at defibrillation threshold testing (DFT) in four patients with ischemic cardiomyopathy pretransplantation. We examined VF in these same four hearts in an ex vivo human Langendorff posttransplantation. VF from DFT was compared with VF from the electrodes from a similar region in the right ventricular endocardium in the Langendorff using two parameters: the scale distribution width (extracted from continuous wavelet transform) and VF mean cycle length (CL). In a second substudy group where multielectrode phase mapping could be performed, we examined early VF intraoperatively (in vivo open chest condition) in three patients with left ventricular cardiomyopathy. We investigated early VF in the hearts of three patients in an ex vivo Langendorff and compared findings with intraoperative VF using two metrics: dominant frequency (DF) assessed by the Welch periodogram and the number of phase singularities (lasting >480 ms). Wavelet analysis (P = 0.9) and VF CL were similar between the Langendorff and the DFT groups (225 ± 13, 218 ± 24 ms; P = 0.9), indicating that wave characteristics and activation rate of VF was comparable between the two models. Intraoperative DF was slower but comparable with the Langendorff DF over the endocardium (4.6 ± 0.1, 5.0 ± 0.4 Hz; P = 0.9) and the epicardium (4.5 ± 0.2, 5.2 ± 0.4 Hz; P = 0.9). Endocardial phase singularity number (9.6 ± 5, 12.1 ± 1; P = 0.6) was lesser in number but comparable between in vivo and ex vivo VF. VF dynamics in the limited experimental human studies approximates human in vivo VF.


Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA, CCKB and CCKC) in human tumors of the central and peripheral nervous system.
Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.


Quantitative study of 'flame follicles' in skin sections of Shar-pei dogs.
This study determined the frequency of occurrence and the mean number of 'flame follicles' per skin section and assessed their diagnostic significance in cutaneous biopsies of Shar-pei dogs. The number of 'flame follicles' per section was recorded in skin sections from 42 Shar-pei dogs, of which 40 had non-neoplastic skin disease and non-atrophic dermatoses and 2 had healthy skin. Forty-two skin sections from dogs of different breeds served as control specimens, 28 of which were examples of non-neoplastic and non-atrophic dermatoses and 14 were from dogs with healthy skin. Differences among groups were analysed by means of the unpaired Student's t-test. It was concluded that 'flame follicles' were more frequent and found in significantly higher numbers in the Shar-pei group when compared with the control group suggesting that 'flame follicles' in skin sections from Shar-pei dogs do not have the same diagnostic significance as in other breeds.


Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastatic non-small-cell lung cancer.
Prior research shows that introducing palliative care soon after diagnosis for patients with metastatic non-small-cell lung cancer (NSCLC) is associated with improvements in quality of life, mood, and survival. We sought to investigate whether early palliative care also affects the frequency and timing of chemotherapy use and hospice care for these patients. This secondary analysis is based on a randomized controlled trial of 151 patients with newly diagnosed metastatic NSCLC presenting to an outpatient clinic at a tertiary cancer center from June 2006 to July 2009. Participants received either early palliative care integrated with standard oncology care or standard oncology care alone. By 18-month follow-up, 133 participants (88.1%) had died. Outcome measures included: first, number and types of chemotherapy regimens, and second, frequency and timing of chemotherapy administration and hospice referral. The overall number of chemotherapy regimens did not differ significantly by study group. However, compared with those in the standard care group, participants receiving early palliative care had half the odds of receiving chemotherapy within 60 days of death (odds ratio, 0.47; 95% CI, 0.23 to 0.99; P = .05), a longer interval between the last dose of intravenous chemotherapy and death (median, 64.00 days [range, 3 to 406 days] v 40.50 days [range, 6 to 287 days]; P = .02), and higher enrollment in hospice care for longer than 1 week (60.0% [36 of 60 patients] v 33.3% [21 of 63 patients]; P = .004). Although patients with metastatic NSCLC received similar numbers of chemotherapy regimens in the sample, early palliative care optimized the timing of final chemotherapy administration and transition to hospice services, key measures of quality end-of-life care.


Effects of Pod Removal on Metabolism and Senescence of Nodulating and Nonnodulating Soybean Isolines: II. Enzymes and Chlorophyll.
The objectives of this work were to determine the effect of sink strength (presence or absence of pods) and nitrogen source (nodulating versus nonnodulating plants) on enzymic activities, chlorophyll concentration, and senescence of soybean (Glycine max [L.] Merr. cv Harosoy) isolines. A 2-year (1981-1982) field study was conducted.For both nodulated and nonnodulated plants, ribulose bisphosphate carboxylase (RuBPCase) activity of upper-canopy leaves was decreased by pod removal in both years, while chlorophyll concentration was decreased in 1981 only. Nonnodulated plants had lower RuBPCase activity in 1981 and lower chlorophyll concentration in both years compared with nodulated plants. In both years, and for all treatments, RuBPCase activity and chlorophyll began to decline at about the same time, but the rate of decline was less for depodded than for podded plants. Leaves in the middle and lower parts of the canopy had similar RuBPCase activity and chlorophyll concentration trends as upper-canopy leaves for all treatments.Profiles of nitrate reductase activity (NRA) were similar for all treatments in both 1981 and 1982. Acetylene reduction profiles were similar for nodulated-podded and nodulated-depodded plants. The peak and decline in NRA profiles preceded the peak and decline in acetylene reduction profiles. The rate of decline in acetylene reduction activity was less for depodded plants, especially in 1982, but activities reached zero by the final sampling time. Thus, nodule senescence was not prevented by pod removal.Based on seasonal profiles of RuBPCase activity, chlorophyll, NRA, and acetylene reduction activity, the initiation of senescence appeared to occur at the same approximate time for all treatments and, thus, did not depend on the presence or absence of pods or nodules. The hypothesis that nodules act as a nitrogen source and carbohydrate sink to delay senescence in the absence of pods was not correct.


Variable Effects of Nitrate on ATP-Dependent Proton Transport by Barley Root Membranes.
The effects of NO(3) (-) and assay temperature on proton translocating ATPases in membranes of barley (Hordeum vulgare L. cv California Mariout 72) roots were examined. The membranes were fractionated on continuous and discontinuous sucrose gradients and proton transport was assayed by monitoring the fluorescence of acridine orange. A peak of H(+)-ATPase at 1.11 grams per cubic centimeter was inhibited by 50 millimolar KNO(3) when assayed at 24 degrees C or above and was tentatively identified as the tonoplast H(+)-ATPase. A smaller peak of H(+)-ATPase at 1.16 grams per cubic centimeter, which was not inhibited by KNO(3) and was partially inhibited by vanadate, was tentatively identified as the plasma membrane H(+)-ATPase. A step gradient gave three fractions enriched, respectively, in endoplasmic reticulum, tonoplast ATPase, and plasma membrane ATPase. There was a delay before 50 millimolar KNO(3) inhibited ATP hydrolysis by the tonoplast ATPase at 12 degrees C and the initial rate of proton transport was stimulated by 50 millimolar KNO(3). The time course for fluorescence quench indicated that addition of ATP in the presence of KNO(3) caused a pH gradient to form that subsequently collapsed. This biphasic time course for proton transport in the presence of KNO(3) was explained by the temperature-dependent delay of the inhibition by KNO(3). The plasma membrane H(+)-ATPase maintained a pH gradient in the presence of KNO(3) for up to 30 minutes at 24 degrees C.


The right time and the left time: Spatial associations of temporal cues affect target detection in right brain-damaged patients.
Humans map timewords such as "yesterday" or "future" onto a mental timeline that holds temporally earlier events on the left side of space and temporally later events on the right side. The perception of time and spatial mapping both are partially subserved by right temporo-parietal brain regions. We tested stroke patients with right-hemisphere lesions on a spatio-temporal cueing task to see whether spatial associations of noninformative temporal cues would elicit the same cognitive deficits as do typical stimulus-driven exogenous cues. While our right brain-damaged patients were able to maintain a mental timeline with words referring to the past sitting to the left and words referring to the future sitting to the right, we also observed that the typical deficit in disengaging from incongruently cued locations persists for noninformative cues that are mapped onto a mental spatial continuum.


A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression.
A growing number of long nuclear-retained non-coding RNAs (ncRNAs) have recently been described. However, few functions have been elucidated for these ncRNAs. Here, we have characterized the function of one such ncRNA, identified as metastasis-associated lung adenocarcinoma transcript 1 (Malat1). Malat1 RNA is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when RNA polymerase II-dependent transcription is active. Knock-down studies revealed that Malat1 modulates the recruitment of SR family pre-mRNA-splicing factors to the transcription site of a transgene array. DNA microarray analysis in Malat1-depleted neuroblastoma cells indicates that Malat1 controls the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippocampal neurons, knock-down of Malat1 decreases synaptic density, whereas its over-expression results in a cell-autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance.


Improving the LIE Method for Binding Free Energy Calculations of Protein-Ligand Complexes.
In this work, we introduced an improved linear interaction energy (LIE) method parameterization for computations of protein–ligand binding free energies. The protocol, coined LIE-D, builds on the linear relationship between the empirical coefficient γ in the standard LIE scheme and the D parameter, introduced in our work. The D-parameter encompasses the balance (difference) between electrostatic (polar) and van der Waals (nonpolar) energies in protein–ligand complexes. Leave-one-out cross-validation showed that LIE-D reproduced accurately the absolute binding free energies for our training set of protein–ligand complexes (<|error|> = 0.92 kcal/mol, SDerror = 0.66 kcal/mol, R(2) = 0.90, QLOO(2) = 0.89, and sPRESS(LOO) = 1.28 kcal/mol). We also demonstrated LIE-D robustness by predicting accurately the binding free energies for three different protein–ligand systems outside the training data set, where the electrostatic and van der Waals interaction energies were calculated with different force fields.


Multi-pulsed white light sintering of printed Cu nanoinks.
Pulse management of white light to maximize the sintering efficiency of a rapid (msec) and substrate-protective method, intense pulsed light (IPL), was studied systematically with a printable Cu nanoink. An excessive pulse energy that induces deleterious defects on the Cu film along with damage on a plastic substrate was dissipated into multiple sub-pulses while maintaining a total energy budget over the threshold level for successful Cu sintering. Electrical properties of the metal layers were analyzed in conjunction with pulse formation factors such as average energy, pulse duration, peak power and pulse number to determine their respective effects on IPL sintering. In the quantitative results, the optimized sintering conditions of copper nanoparticles with a mean diameter of 30 nm and a fixed total irradiated pulse energy of 32 J cm(-2) were a pulse number and pulse width of > 4 and < 3 msec, respectively.


AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.
We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.


Correlation of lipolytic and lipogenic actions of synthetic peptides with structure.
The effects of various synthetic peptides on basal and ACTH-stimulated lipolysis in fat cells were examined. Glu-Arg-Gly-Phe-Phe-Phe possessed lipolytic activity and increased ACTH-stimulated lipolysis at concentrations higher than 0.5 mumol/ml. Glu-Arg-Gly-Phe-Phe-Tyr did not cause any release of FFA from fat cells. Glu-Arg-Gly-Leu-Leu-Leu had no lipolytic activity but inhibited ACTH-stimulated lipolysis at concentrations higher than 0.25 mumol/ml. Glu-Arg-Gly-Leu-Leu-Leu also inhibited epinephrine-stimulated lipolysis. The effects of the peptides on basal and insulin-stimulated lipogenesis in fat cells were examined. Glu-Arg-Gly-Phe-Phe-Tyr increased both basal and insulin-stimulated lipogenesis. A tripeptide, Glu-Arg-Gly, inhibited both basal and insulin-stimulated lipogenesis. Glu-Arg-Gly-Leu-Leu-Leu had no effect on either basal or insulin-stimulated lipogenesis. Glu-Arg-Gly-Phe-Phe-Phe and ACTH, which elicit FFA release from fat cells, also stimulated formation of [14C]triglyceride from [14C]glucose.


The family history: An integral component of paediatric health assessment.
Conducting the paediatric health history is a vital skill for the paediatrician. However, published guidelines on this topic often fail to emphasize the value that the family history adds to paediatric health assessment. For the healthy child, the family history may reveal risk factors for juvenile and/or adult-onset conditions, the adverse effects of which may be ameliorated with medical intervention or surveillance. For the child with a health problem, a detailed family history may help to guide the clinician through the diagnostic and treatment processes.


[Myocardial impairment in asphyxiated newborn piglets].
To establish a piglet model of acute hypoxic myocardial impairment. Nineteen newborn piglets were divided into two groups: control group (CON, n = 8) and asphyxia group (ASP, n = 11). In ASP group, asphyxia was induced by disconnecting the animal from the ventilator and clamping the inhalation tubing for 10 minutes. Six hours after cardiopulmonary resuscitation (CPR), the levels of serum creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were detected. Cardiac functions were evaluated by echocardiography. Parameters included left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), ratio of peak E velocity and peak A velocity of mitral flow and tricuspid flow (MVE/A and TVE/A), ratio of peak velocity and a velocity of mitral annulus motion and tricuspid annulus motion (MVe/a and TVe/a), isovolumic relaxation time of left ventricle (LVIRT), index of mitral regurgitation and tricuspid regurgitation (MR and TR). The CON group was examined at the corresponding time points. The pathologic changes in piglets' hearts were examined. The myocardial histopathologic damage score (MHDS) was used to evaluate the severity of myocardial impairments. Six hours after CPR, the CK-MB and cTnT in ASP group [(423 +/- 156) IU/L and (0.85 +/- 0.64) microg/L] were both higher than those in CON group [(213 +/- 30) IU/L and (0.08 +/- 0.02) microg/L, P < 0.01]. The LVEF, RVEF, TVE/A, MVe/a and TVe/a in ASP group [(59.6 +/- 8.6)%, (60.2 +/- 7.1)%, 0.79 +/- 0.21, 0.77 +/- 0.12 and 0.78 +/- 0.19, respectively] were all lower than those in CON group [(67.5 +/- 6.9)%, (68.8 +/- 7.4)%, 1.14 +/- 0.16, 1.19 +/- 0.18 and 1.03 +/- 0.27, respectively, P < 0.05]. The MHDS in ASP group was higher (2.82 +/- 0.98) than that in CON group (0.38 +/- 0.53, P < 0.01), but no significant difference was observed in MHDS between the left ventricle and right ventricle. Asphyxia can lead to obvious myocardial impairment in newborn piglet, which could be very useful for the studies of acute hypoxic myocardial impairment in the newborn infants.


Study on Appropriate Rectal Volume for External Irradiation in Patients With Cervical Cancer.
To investigate the appropriate rectal volume for external irradiation of cervical cancer. A retrospective study of 143 patients with cervical cancer who underwent external radiotherapy from January 2017 to September 2020 was conducted. Average rectum volumes and the cumulative dose (V30, V40, V50, D2cc) to organs at risk (bladder, rectum, and small bowel) during radiotherapy were evaluated using the treatment planning system. Rates of radiation cystitis and radiation proctitis were assessed. The median follow-up was 48 months, and the included patients had a median age of 53 years. Patients were divided into 3 groups based on their average rectum volume: Group A: <40 ml; Group B: 40-70 ml; and Group C: ≥70 ml. V30 and V40 in the rectum bladder and small bowel were highest in Group A (mean ± SD standard deviation), but V50 and D2cc in the rectum and bladder were highest in Group C (mean ± SD). Patients in Group B had the lower incidence of both radiation cystitis and radiation proctitis. (p<0.05). For external irradiation in patients with cervical cancer, a rectum volume of 40-70 ml seems most appropriate, whereas >70 ml increases the risk of severe radiation cystitis and radiation proctitis, and <40 ml increases the risk of mild radiation cystitis and mild radiation proctitis.


[Post-traumatic os odontoideum].
This is a report about a 20-month-old child with acquired os odontoideum caused by a fall. Diagnosis of atlanto-axial instability was eventually made 29 months later after repeated trauma and transitory tetraparesis. Dorsal C1/2 fusion with an autogenic rib graft and plaster fixation for 8 weeks failed; an autogenic iliac bone graft plus external fixation for 12 weeks finally resulted in solid fusion.


Estrogen induces the assembly of a multiprotein messenger ribonucleoprotein complex on the 3'-untranslated region of chicken apolipoprotein II mRNA.
UV cross-linking was used to identify estrogen-induced hepatocyte proteins that bind to apoII mRNA. Probes spanning the entire message revealed the presence of eight estrogen-induced proteins cross-linked to the 3'-untranslated region (UTR), but not to the coding region or the 5'-UTR. Two estrogen-induced proteins of 132 and 50 kDa were either absent or barely detectable in control animals, whereas six additional proteins of 93, 83, 74, 65, 58, and 45 kDa were clearly present in control animals and increased 2-5-fold by estrogen. A similar profile of estrogen-induced proteins was seen with the 3'-UTRs of the estrogen-regulated mRNAs for apoB and vitellogenin II, but not with the 3'-UTRs of the non-estrogen-regulated mRNAs for apoA-I and glyceraldehyde-phosphate dehydrogenase. These findings indicate that the estrogen-induced proteins discriminate among mRNAs and suggest that they interact selectively with the family of estrogen-regulated mRNAs. The estrogen-induced proteins are found in the cytoplasmic fraction of liver extracts, and a subset of them are also found in adrenal glands, testes, heart, brain, and kidneys, but they are estrogen-induced only in the liver. Deletion analysis defined a 150-nucleotide region of the apoII 3'-UTR that is necessary for maximal binding of the estrogen-induced proteins. An internal deletion of endonucleolytic cleavage sites previously identified within the apoII 3'-UTR selectively reduced the binding of the 58-kDa protein. These findings reveal remarkable complexity in estrogen-stimulated protein-RNA interactions within the 3'-UTRs of estrogen-regulated mRNAs. These proteins may participate in the mRNA degradation process or in other aspects of cytoplasmic mRNA metabolism that accompany estrogen-stimulated vitellogenesis.


Radiogenic leukemia revisited.
Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x-ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans.


[Analysis of the clinical value of ultrasound attenuation parameters in evaluating liver steatosis degree in patients with chronic liver disease].
Objective: To evaluate the clinical value of ultrasound attenuation parameters (UAP) in diagnosing the liver steatosis degree in patients with chronic liver disease, and to explore the relevant factors that affect UAP detection values. Methods: 130 cases with chronic liver disease diagnosed as liver steatosis by liver biopsy during January 2014 to May 2019 were selected from the Hepatology Department of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University. UAP and liver stiffness (LSM) were detected by iLivTouch, and the body mass index (BMI) was calculated. Simultaneously, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBil), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels and peripheral platelet (PLT) counts were measured. The correlation between UAP and liver steatosis was analyzed based on the liver histopathological results. SPSS 21.0 statistical software was used for statistical analysis. Receiver operating characteristic curve (ROC) was used to analyze the accuracy and specificity of UAP in the diagnosis of liver steatosis in patients with chronic liver disease. Spearman's rank correlation analysis was used to study the relevant factors affecting UAP value. Results: The histopathological changes of liver biopsy showed that there were 43 cases of grade F1, 47 cases of F2, 32 cases of F3 and 8 cases of F4. UAP and BMI (r = 0.363, P < 0.001), and UAP and liver steatosis degree (r = 0.380, P < 0.001) were positively correlated. BMI and the liver steatosis degree were independent predictors of UAP value. The cut-off points for UAP to diagnose liver steatosis degree were 276 dB/m for F≥2, 288 dB/m for F≥2, 293 dB/m for F≥3, and F = 4, respectively. The sensitivity and specificity was 0.379, 0.500, 0.750, and 0.930, 0.922, 0.836, respectively. Conclusion: Ultrasonic attenuation parameters cannot only determine the presence or absence of liver steatosis in patients with chronic liver disease, but also can better assess the liver steatosis degree.


[The structure for an analysis of the determinants of infant and child mortality].
An attempt is made to develop models that can explain the age patterns of infant and child mortality. The authors first review factors affecting infant and child mortality, identifying both the factors involving exposure to risk and those governing the individual's resistance to disease. Consideration is also given to the effect of therapeutic care. An indicator of the structure of child mortality is then developed to be "used as a dependent variable in a model of linear regression which includes mortality level, sex, climate, time and income as explanatory variables." The results indicate that the mortality level is the key factor affecting the age pattern of mortality during childhood and that the mortality of both sexes is very similar between one and five years of age. Of the other factors considered, only climate has a significant impact on mortality. (summary in ENG, SPA)


Hypnosis for irritable bowel syndrome: the quest for the mechanism of action.
Irritable bowel syndrome (IBS) is a very common condition in the Western part of the world, and it accounts for a large proportion of the workload of a gastroenterologist. Unfortunately, the pathogenesis and pathophysiology of the syndrome are incompletely understood, and the treatment options are limited. However, hypnotherapy is one treatment option that has proven to be very useful in IBS. The mechanisms of action explaining why hypnosis is effective for IBS are not altogether known, but recent studies have shed some light on this issue. These studies, and what can be learned from them about how hypnosis impacts IBS, are reviewed in this article. Hypnosis may affect IBS partly through changes in colorectal sensitivity and improvement in psychological factors. The effects on GI motility and the autonomic nervous system are less clear and need further evaluation.


Synthesis of antibacterial surfaces by plasma grafting of zinc oxide based nanocomposites onto polypropylene.
Antibacterial polymer surfaces were designed using ZnO nanoparticles as a bactericide. Mineral encapsulated nanoparticles were grafted onto activated polymer surfaces through their shells. Polypropylene (PP) surfaces were treated using an innovative process coupling core-shell technology and plasma grafting, well-known techniques commonly used to obtain active surfaces for biomedical applications. First, ZnO nanoparticles were encapsulated by (co)polymers: poly(acrylic acid) (PAA) or a poly(methyl methacrylate-co-methacrylic acid) copolymer [P(MMA-MA)]. Second, PP substrates were activated using plasma treatment. Finally, plasma-treated surfaces were immersed in solutions containing the encapsulated nanoparticles dispersed in an organic solvent and allowed to graft onto it. The presence of nanoparticles on the substrates was demonstrated using Fourier-Transform Infrared Spectroscopy (FTIR) analysis, Scanning Electron Microspcopy (SEM)/Energy-Dispersive X-ray (EDX), and Atomic Force Microscopy (AFM) studies. Indeed, the ZnO-functionalized substrates exhibited an antibacterial response in Escherichia coli adhesion tests. Moreover, this study revealed that, surprisingly, native ZnO nanoparticles without any previous functionalization could be directly grafted onto polymeric surfaces through plasma activation. The antibacterial activity of the resulting sample was shown to be comparable to that of the other samples.


Hydroarylations of heterobicyclic alkenes through rhodium-catalyzed directed C-H functionalizations of S-aryl sulfoximines.
Rhodium-catalyzed directed CH-functionalizations have been used in hydroarylations of heterobicyclic alkenes with NH-sulfoximines. Unexpectedly, the bicyclic framework is retained, resulting in the formation of addition products being attractive intermediates for functionalized molecules that are difficult to prepare by other means.


A qualitative study of handovers at shift changeovers in five care homes for older people in England.
It is widely acknowledged that inadequate handovers are associated with putting patients at risk in clinical settings; however, handover practices have received little attention in other 24-hr settings such as long-stay residential care facilities. This study aimed to explore the perceived purpose and organisational processes involved in the handover of information between shifts of staff caring for older residents in five care homes in England. The study took an ethnographic approach to fieldwork, undertaken between February and June 2016. It consisted of observations of handovers (n = 12) and interviews with managers, Registered Nurses (RNs) and care assistants (n = 27) working day and night shifts. Interview transcripts and observation notes were analysed within NVivo using a matrix approach. Handovers were highly variable in all five care homes in relation to their timings, locations, content and participants. Managers and RNs highlighted handovers as an opportunity for risk assurance, supervision, team building, staff education and monitoring of residents' clinical status. In comparison, care assistants considered the purpose of handovers to be prepared for the responsibilities of working a shift. The discussion addresses implications of these findings, particularly consideration of how best use can be made of RN skills and knowledge in handovers. Research is needed to identify whether care home resident safety can be linked to handover practices and how the presence of RNs in handovers in care homes affects this. Care home managers, RNs and care workers may find this research useful in practice when considering how best to organise handovers and deploy staff in care homes for older people.


Panel on deliberate G-induced loss of consciousness: introduction.
Over the last decade, G-induced loss of consciousness (G-LOC) has been recognized as a significant operational problem for pilots of high performance aircraft in both the U.S. Air Force and U.S. Navy. Consequently, government laboratories have initiated research studies to learn more about the G-LOC phenomenon in an attempt to reduce its hazards. Many of these studies require the occurrence of LOC during their conduct. For this reason, animal models have been developed to use in these studies. However, even though sophisticated animal models such as baboons can be taught to perform tasks before and after G-LOC has occurred, these models have deficiencies that can be overcome only by the use of human volunteers who willingly submit to G-LOC studies on the centrifuge. Such human G-LOC studies began in World War II and continue today. These studies are presently conducted without guidelines regarding subject selection, numbers of G-LOCs allowed per subject per unit time, restraint systems, or specific medical examinations required before, during, and after each episode of LOC, or after each completed study. This panel will discuss what is known about the pathophysiology of G-LOC, the limitations of animal models in these types of studies, the possible medical and psychological sequelae, and the legal implications of conducting deliberate G-LOC research. We hope that the information developed by this panel will be useful to laboratory human-use review committees in determining the requirements and the nature of guidelines for conducting such studies.


Clinical Profile and Outcome Following Exchange Transfusion for Neonatal Jaundice in a Tertiary Care Centre.
Phototherapy has reduced the need for exchange transfusion (ET) to manage jaundiced neonates. Hence there are concerns about increased risk of complication due to lack of opportunity to sustain skills in performing ET. We studied the complications and treatment outcomes of neonates treated for jaundice with ET. A retrospective observational study was conducted from June 2013 to June 2020 in a tertiary care hospital in India. All neonates treated with ET for jaundice were included. Twenty-eight neonates underwent 31 ET during the study period. Their mean gestational age and birth weight were 37 weeks and 3200 g, respectively. Predisposing factor for jaundice observed were Coomb's positive status (11), hepatosplenomegaly suggesting hemolysis (3), cephalhematoma (2) and birth asphyxia (1). Abnormal neurological status before ET was seen in seven neonates. Adverse clinical events that happened during or within 8 h after ET were desaturation (4), tachycardia (3), tachypnea (2), bradycardia (2), shock (2) and temperature instability (2). One neonate developed acute kidney injury after ET and required peritoneal dialysis. Abnormal lab parameters observed during or within 8 h after ET were hypocalcemia (20), anemia (8), hypokalemia (7), hypernatremia (3), thrombocytopenia (3) and hyperkalemia (2). Post ET sepsis was seen in five neonates: two had only blood culture positive sepsis, two had bone and joint infection and one had liver abscess. The neonates undergoing ET are at high risk of developing complications which may be life threatening. Hence careful monitoring during the procedure is needed.


Attitudes about skin cancer prevention: a qualitative study.
Skin cancer represents a significant threat to the health and well-being of Americans. By engaging in both primary and secondary preventive behaviors, individuals can reduce their risks of developing skin cancer. Focus groups were used as a qualitative technique to explore the similarities and differences between those who practiced skin cancer prevention (a high-concern group) and those who did not (a low-concern group). Transcripts from the discussions were analyzed to identify themes regarding participants' attitudes, beliefs, and practices about skin cancer prevention. Seven themes emerged from the data: 1) benefits of sun exposure; 2) salience of skin cancer prevention; 3) perceived seriousness of the sun's harmful effects; 4) personal connection to skin cancer; 5) media attention regarding skin cancer; 6) problems with sunscreens; and 7) preventive health "have-tos." To improve skin cancer prevention, health education interventions must attend to individuals' attitudes about sun exposure and address the barriers related to them.


The impact of Acinetobacter baumannii infections on outcome in trauma patients: a matched cohort study.
To determine the impact of Acinetobacter baumannii infection on the outcome of trauma patients. A retrospective 1:2-matched cohort study. Level I trauma intensive care unit patients with confirmed Acinetobacter baumannii infection were defined as cases. Thirty-one Acinetobacter baumannii patients were matched to 62 controls with evidence of infection caused by other microorganisms. There were 12 matching criteria, including focus of infection, demographics, severity, and characteristics of injury. In-hospital mortality rate, intensive care unit length of stay, and complications of Acinetobacter baumannii including multidrug-resistant strains in patients were compared to those of their controls; 81% had hospital-acquired pneumonia, 13% had bloodstream infections, and 6% had urinary tract infections in both groups. Acinetobacter baumannii cultures were multidrug resistant in 42% (13/31) of cases. The initial empirical antibiotic therapy was adequate in 71% (22/31). Although the in-hospital mortality was higher in the Acinetobacter baumannii group (16% vs. 13%; odds ratio, 1.23; 95% confidence interval, 0.38-4.36; p = .67), the difference did not reach statistical significance. Using the test of equivalence or clinical indifference, the impact of an Acinetobacter baumannii infection on mortality is inconclusive. This applies also to multidrug-resistant strains. Overall intensive care unit stay was prolonged for Acinetobacter baumannii when compared to controls (median, [range], 28 [7-181] days vs. 17 [2-130] days, respectively; p = .05). ARDS and acute liver failure were more frequent in the Acinetobacter baumannii group compared to the control group (35% vs. 15%; odds ratio, 3.24; 95% confidence interval, 1.17-5.48; p = .02 and 26% vs. 10%; odds ratio, 3.25; 95% confidence interval, 3.25-10.40; p = .04). In this single-center experience, Acinetobacter baumannii infection, including multidrug-resistant strains, has inconclusive impact on mortality in a cohort of trauma patients. Larger studies are needed to support a definite conclusion. Acinetobacter baumannii infection was, however, associated with a longer intensive care unit stay and a higher rate of organ failure.


Pancreatic cancer: epidemiology and risk factors.
Ductal adenocarcinoma of the pancreas has an incidence of approximately 10 per 100,000 population per year. This number pertains to Europe, North America and parts of South America (Argentina). Men are more often afflicted than women (female:male ratio of about 1:1.5, though reports vary). There has been a very small but steady increase in the incidence over the last 50 years. Unfortunately, numbers for incidence and mortality are still practically identical for this cancer. The peak of incidence is between 60 and 80 years of age. In absolute numbers, there are 8,000 cases diagnosed annually in Germany, and 33,000 in the US. Pancreatic cancer at <40 years of age is extremely rare (2 cases per million per year), but among 80-year-olds, the incidence is about 200 new cases per 100,000 population per year. In men, carcinoma of the pancreas is the fourth most common cause of cancer death after lung, prostate and colorectal cancer. In women, it is the fifth most common cause of cancer death. Risk factors for pancreatic cancer include high-fat diet, smoking, chronic pancreatitis, primary sclerosing cholangitis, hereditary pancreatitis, family history of pancreatic cancer and diabetes mellitus. In chronic pancreatitis, the risk for pancreatic cancer is increased 20-fold, in hereditary pancreatitis it is 60-fold higher than in the general population. In a kindred with 2 first-degree relatives with pancreatic cancer, the risk for pancreatic cancer for other members of that kindred is 7-fold higher.


Decree relating to health education and information on youth as well as to aid and assistance to families in areas relating to contraception and responsible parenting, 10 July 1984.
This Decree requires various organizations in the French Community of Belgium, which supply aid and information on sexuality, marriage, and the family, to furnish their personnel with a list of approved centers and documentation containing the necessary legal, technical, and medical information for couples and persons who request it in the area of contraception and responsible parenting. It also requires the personnel of such organizations, as well as hospitals, to give to women in distress the necessary technical and medical aid to deal with difficulties in using contraceptive methods. Finally, it requires educational establishments to provide, within the framework of biology and social and moral science courses, information on the legal, technical, moral, and medical problems posed by responsible parenting and contraceptives.


Review of Rhabdiasidae (Nematoda) from the Holarctic.
The review deals with the species of Rhabdiasidae Railliet, 1915 occurring in the Holarctic. Descriptions of 26 species from the genera Rhabdias Stiles et Hassal, 1905 (21 species), Entomelas Travassos, 1930 (4 species), and KurolonemaSzczerbak et Sharpilo, 1969 (1 species) are presented. Additionally, 5 species of Rhabdias are listed as species inquirenda, and 4 species are included into the review, since they have been reported close to south-eastern border of Palaearctic (the exact distribution is unknown). Keys to the Holarctic species and diagnoses of the genera are provided. An overview of the information on the biology, morphology and taxonomy of Rhabdiasidae is also presented, as well as the host-parasite list of Holarctic Rhabdiasidae.


[Acute abdominal pain in childhood].
Acute abdominal pain in children occurs often and requires rapid clarification. Hints as to the condition are often given by the first impression and the case history of the patient. When the clinical examination and laboratory results do not lead to a clear finding, imaging methods such as a sonography can clarify the case. The most common cause for abdominal pain in infants is acute enteritis, mostly brought about by rotaviruses. Additional diagnoses are abdominal hernia, malrotation, hypertrophic pyloric stenosis, invagination or gastroesophageal reflux. In school-age children, the classic finding is "appendicitis". This should be differentiated from constipation, gastritis, pancreatitis, sigmoid volvulus, bowel and intestinal obstruction or, perhaps, gallstone trouble.


Uncontrollable prurigo nodularis effectively treated by roxithromycin and tranilast.
Treatment of prurigo nodularis (PN) is often very difficult even with strong corticosteroid dressing and other available means. Macrolide roxithromycin (RXM) is used in consideration of its immunosuppressive effects in treating several skin disorders. Tranilast (N-(3,4-dimethoxycinnamoyl) is useful for treating atopic disorders and hypertrophic scars as well, suggesting its capacity to inhibit fibroblast proliferation. More adequate and effective therapy for this disorder has been requested. We report 3 cases of uncontrollable PN treated with 300 mg/day roxithromycin and 200 mg/day tranilast. Complete and/or remarkable regression of PN was observed on treatment with roxithromycin and tranilast in combination within 4 to 6 months. The 2 agents in combination can be used effectively for the treatment of uncontrollable PN.


The Rett syndrome protein MeCP2 regulates synaptic scaling.
Synaptic scaling is a form of homeostatic synaptic plasticity characterized by cell-wide changes in synaptic strength in response to changes in overall levels of neuronal activity. Here we report that bicuculline-induced increase in neuronal activity leads to a decrease in mEPSC amplitude and a decrease in expression of the AMPA receptor subunit GluR2 in rat hippocampal cultures. Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A. Downregulation of MeCP2 by shRNA expression or genetic deletion blocks the bicuculline-induced decrease in GluR2 expression and mEPSC amplitude. These observations indicate that MeCP2 mediates activity-dependent synaptic scaling, and suggest that the pathophysiology of Rett syndrome, which is caused by mutations in MeCP2, may involve defects in activity-dependent regulation of synaptic currents.


Mammographic practice and dosimetry in Britain.
A survey of mammographic techniques and dosimetry in 61 NHS centres in Britain has been completed. Physical parameters measured at each centre included tube output, half-value thickness, peak kilovoltage, surface dose and percentage depth dose. Ionisation and thermoluminescence dosimetry were employed and image quality was assessed subjectively using a test phantom. Absorbed doses are given at the plane surface of an average-sized, 5 cm thick homogenous breast composed of 50% fat and 50% water. The doses fall naturally into the four combinations of molybdenum (Mo) and tungsten (W) targets and film (F) and xerox (X) receptors. The Mo/X group produced the best images of the phantom but also the highest mean dose of 3.26 cGy (rad) for a cranio-caudad (c-c) view and its use does not seem justified for asymptomatic screening. The Mo/Lo-Dose or MIN-R film combination gave a mean dose of 0.95 cGy(rad) for a c-c view whereas the W/X group gave 0.89 cGy(rad) and superior image quality. The W/F group gave the poorest image quality and its continued use for mammography is questionable.


Aggregation Kinetics of Polysorbate 80/m-Cresol Solutions: A Small-Angle Neutron Scattering Study.
Polysorbate 80 (PS80), a nonionic surfactant used in pharmaceutical formulation, is known to be incompatible with m-cresol, an antimicrobial agent for multi-dose injectable formulations. This incompatibility results in increased turbidity caused by micelle aggregation progressing over weeks or longer, where storage temperature, ionic strength, and component concentration influence the aggregation kinetics. Small-angle neutron scattering (SANS) analysis of PS80/m-cresol solutions over a pharmaceutically relevant concentration range of each component reveals the cause of aggregation, the coalescence mechanism, and aggregate structure. PS80 solutions containing m-cresol concentrations below ≈2.0 mg/mL and above ≈4.5 mg/mL are kinetically stable and do not aggregate over a 50 h period. At 5 mg/mL of m-cresol, the mixture forms a kinetically stable microemulsion phase, despite being well below the aqueous solubility limit of m-cresol. Solutions containing intermediate m-cresol concentrations (2.0-4.5 mg/mL) are unstable, resulting in aggregation, coalescence, and eventual phase separation. In unstable solutions, two stages of aggregate growth (nucleation and power-law growth) are observed at m-cresol concentrations at or below ≈3.6 mg/mL. At higher m-cresol concentrations, aggregates experience a third stage of exponential growth. A single kinetic model is developed to explain the stages of aggregate growth observed in both kinetic mechanisms. This work establishes the phase diagram of PS80/m-cresol solution stability and identifies component concentrations necessary for producing stable formulations.


Urinary neutrophil gelatinase-associated lipocalin level as a biomarker of acute kidney injury following extracorporeal shock wave lithotripsy.
Although extracorporeal shock wave lithotripsy (ESWL) is minimally invasive and highly efficient for the management of kidney stones, adverse effects have been described. Available indicators of renal function exhibit insufficient sensitivity in acute renal injury (AKI). We aimed to evaluate the severity of the kidney tissue response to ESWL injury by measuring the urinary neutrophil gelatinase-associated lipocalin (uNGAL), which can indicate AKI in its early phase. The prospective, controlled study included 62 patients with nephrolithiasis undergoing single ESWL treatment. uNGAL level was measured before the procedure, and 6 h and 12 h after. The median uNGAL level increased by 126.0%, 6 h after ESWL (p <0.001). The growth rate continued and 12 h after was higher by 583.7%, compared to the pre-treatment level (p <0.001). The median value of estimated glomerular filtration rate (eGFR) dropped by 15.3% 12 h after the treatment (p <0.001). It increased by 5.0% in the period 7 days to 3 months after (p <0.001) and after 3 months it was lower by 10.1% compared to pre-ESWL values (p <0.001). uNGAL level after 12 h was significantly negatively associated with eGFR, 12 h, 7 days and 3 months after the ESWL. The sensitivity of uNGAL 12 h after ESWL was 60.6%; its specificity was 75.0%, with a positive predictive value of 74.0% and negative predictive value of 61.7%. uNGAL appears to be a useful biomarker for the assessment and prediction of AKI. It was noticed that uNGAL had the highest predictive value 12 h after the ESWL treatment.


Somatic stem cell research for neural repair: current evidence and emerging perspectives.
Recent evidence supports the existence of adult mammalian stem cell subpopulations, particularly within the bone marrow, that may be able to "transdifferentiate" across tissue lineage boundaries, thus offering an accessible source for therapeutic applications even for neural tissue repair. However, the difficulties in reproducing some experimental data, the rarity of the transdifferentiation events and observations that cell fusion may be an alternative explanation argue against the idea of stem cell plasticity. Investigations going beyond descriptive experiments and more mechanicistic approaches may provide a more solid foundation to adult stem cell therapeutic potential.


The post-reinforcement pause.
Measurements of the post-reinforcement pause and response rate were obtained from four birds on a range of fixed ratio schedules from 25 to 150. The results indicated a consistent increase in the length of the pause as the ratio was increased. Response rate tended to decrease, but these data were less consistent and some reversals were apparent.


Effect of nighttime bedroom light exposure on mood episode relapses in bipolar disorder.
A previous cross-sectional study reported that nighttime light is associated with increased occurrence of manic symptoms in bipolar disorder; however, the longitudinal association between nighttime light and subsequent mood episode relapses remains unclear. We determined whether bedroom nighttime light was associated with mood episode relapses in patients with bipolar disorder. This prospective cohort study included 172 outpatients with bipolar disorder who participated in an Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. A portable photometer was used to measure illuminance in the bedroom from bedtime to rising time during 7 consecutive nights for baseline assessment. Then, the participants were assessed at a 2-year follow-up for mood episode relapses. Of the 172 participants, 157 (91%) completed the 2-year follow-up, and 39 (22%) experienced manic or hypomanic episodes (with or without mixed features), during that time. In the Cox proportional-hazards model, the hazard ratio (HR) for manic/hypomanic episode relapses was significantly higher when the average nighttime illuminance was ≥3 lux (n = 71) than when it was <3 lux (n = 101; HR, 2.54; 95% confidence interval (CI), 1.33-4.84). In the multivariable model adjusted for a propensity score in relation to nighttime light, the relationship remained significant (HR, 2.17; 95% CI, 1.04-4.52). The association between nighttime light and depressive episode relapses was not significantly different. Keeping the bedroom dark at night may prevent hypomanic and manic episodes.


The roots of Nardostachys jatamansi inhibits lipopolysaccharide-induced endotoxin shock.
Nardostachys jatamansi (NJ) has been used in the treatment of inflammatory diseases. However, it is not clear how NJ produces anti-inflammatory effects. In the present study, using an experimental model of lipopolysaccharide (LPS)-induced endotoxin shock, the protective effects and mechanisms of action of NJ were investigated. The water extract of roots of NJ was administrated to mice orally (1, 5, and 10 mg/kg) 1 h after or before LPS challenge. The administration of NJ inhibited LPS-induced endotoxin shock and the production of inflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-α/β. Murine peritoneal macrophages were used to determine the production of inflammatory mediators. In peritoneal macrophages, NJ also inhibited LPS-induced production of inflammatory mediators, such as IL-1β, IL-6, TNF-α, and IFN-α/β. In addition, NJ reduced the activation of mitogen-activated protein kinases (MAPKs) and the level of expression of interferon regulatory factor (IRF)-1 and IRF-7 mRNA. Furthermore, post-treatment with NJ reduced LPS-induced endotoxin shock and the production of inflammatory mediators. These results suggest that NJ inhibits endotoxin shock by inhibiting the production of IL-1β, IL-6, TNF-α, and IFN-α/β through the inhibition of MAPKs activation and IRF induction.


Structure-dependent photodegradation of carotenoids accelerated by dimethyl tetrasulfide under UVA irradiation.
Carotenoids are used in wide-ranging food applications, but they are susceptible to degradation by many factors including light. We examined the photodegradation of five kinds of carotenoids and three kinds of anthocyanins to clarify which structures of pigments were favorable to accelerated degradation by sulfides under UVA irradiation. Under UVA irradiation, crocetin and crocin were decomposed more rapidly in the presence of dimethyl tetrasulfide than in the absence of the sulfide, but not as rapidly as beta-carotene, zeaxanthin and beta-cryptoxanthin were. However, cyanidin was decomposed more slowly in the presence of sulfide than in the absence of sulfide. Moreover, the photodegradation of kuromanin and keracyanin was not affected by the addition of a sulfide. We also examined the mechanism for this accelerated degradation. Normal hexane was more favorable to the photodegradation of beta-carotene than methanol and ethanol. The accelerated degradation was inhibited by free radical scavengers, but enhanced by the addition of deuterium oxide. These results suggest that conjugated double bonds were favorable to the accelerated photodegradation by sulfide and that this reaction was mediated by free radicals.


Regulation of IMP dehydrogenase gene expression by its end products, guanine nucleotides.
To study the regulation of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanine nucleotide biosynthesis, we examined the effects of nucleosides, nucleotides, nucleotide analogs, or the IMPDH inhibitor mycophenolic acid (MPA) on the steady-state levels of IMPDH mRNA. The results indicated that IMPDH gene expression is regulated inversely by the intracellular level of guanine ribonucleotides. We have shown that treatment with guanosine increased the level of cellular guanine ribonucleotides and subsequently reduced IMPDH steady-state mRNA levels in a time- and dose-dependent manner. Conversely, MPA treatment diminished the level of guanine ribonucleotides and increased IMPDH mRNA levels. Both of these effects on the steady-state level of IMPDH mRNA could be negated by cotreatment with guanosine and MPA. The down regulation of IMPDH gene expression by guanosine or its up regulation by MPA was not due to major changes in transcriptional initiation and elongation or mRNA stability in the cytoplasm but rather was due to alterations in the levels of the IMPDH mRNA in the nucleus. These results suggest that IMPDH gene expression is regulated by a posttranscriptional, nuclear event in response to fluctuations in the intracellular level of guanine ribonucleotides.


Identification by a random linker insertion method of a region which suppresses the transforming activity of the raf oncogene.
Activation mechanism of raf oncogene was studied by applying in vitro mutagenesis to its cDNA. Previous studies suggested the presence of an activation suppressing sequence in the amino-terminal half of c-raf product. Loss of the sequence by genetic rearrangement was presumed to convert c-raf to possess transforming activity. To identify such sequence, we prepared cDNA mutants by random linker insertion. Synthetic oligonucleotide linker was inserted into the plasmid containing cDNA at a single and random site. Coupling two different mutants, in-frame deletion mutants were constructed systematically. Analysis of these deletion mutants revealed a region, the loss of which made c-raf activated.


Pre-movement changes in sensorimotor beta oscillations predict motor adaptation drive.
Beta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25 Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline, late adaptation, or aftereffect trials. The changes in beta were not related to measurements of reaction time or reach duration. We also recorded local field potential (LFP) activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during early adaptation. This effect was present when controlling for any influence of the reaction time and reach duration. Overall, the results are consistent with a reduction in pre-movement beta oscillations predicting an increase in adaptive drive in upcoming task performance when motor errors are largest in magnitude and the rate of adaptation is greatest.


High-resolution radioautography of galactose-3H accumulation in rings of hamster intestine.
Radioautography of water-soluble substances has posed a major technical problem for the past decade. Utilizing silicone-impregnated plastic sections of frozen-dried tissue, a quantitative method was developed for studying distribution of (3)H-labeled galactose, mannitol, and phlorizin. The content of a 2-micro band may be measured with an accuracy of +/-20% by light microscopy; radioautographs may also be prepared for the electron microscope. Results with intestinal tissue incubated 1-10 min in vitro and, then, frozen rapidly indicate that the first step in galactose absorption is uphill transport into the brush border of the columnar epithelium. Correction of galactose content for the mannitol space in the brush border suggests that the sugar pump is located at the surface of the microvilli. Further evidence for the surface locus of the glucose-galactose pump was obtained with phlorizin (next paper, reference 40). The galactose content of columnar cell cytoplasm always equalled that of microvilli and no transcellular diffusion gradient could be detected; during the first minutes of incubation, however, a gradient did exist between nucleoplasm and cytoplasm. Downhill exit of galactose from columnar cells may have proceeded either directly across basal membranes to adjacent lamina propria or indirectly via open intercellular spaces. Lastly, even in the absence of muscularis, the connective tissue of the lamina propria constituted enough of a diffusion barrier so that it served as a secondary accumulating compartment for galactose under present in vitro conditions.


A ketogenic diet differentially affects neuron and astrocyte transcription.
Ketogenic diets (KDs) alter brain metabolism. Multiple mechanisms may account for their effects, and different brain regions may variably respond. Here, we considered how a KD affects brain neuron and astrocyte transcription. We placed male C57Bl6/N mice on either a 3-month KD or chow diet, generated enriched neuron and astrocyte fractions, and used RNA-Seq to assess transcription. Neurons from KD-treated mice generally showed transcriptional pathway activation while their astrocytes showed a mix of transcriptional pathway suppression and activation. The KD especially affected pathways implicated in mitochondrial and endoplasmic reticulum function, insulin signaling, and inflammation. An unbiased analysis of KD-associated expression changes strongly implicated transcriptional pathways altered in AD, which prompted us to explore in more detail the potential molecular relevance of a KD to AD. Our results indicate a KD differently affects neurons and astrocytes, and provide unbiased evidence that KD-induced brain effects are potentially relevant to neurodegenerative diseases such as AD.


The role of the two TNF receptors in proliferation, NF-kappa B activation and discrimination between TNF and LT alpha signalling in the human myeloma cell line OH-2.
We wanted to study the role of the two TNF receptors (TNFR) in mediating proliferation and nuclear transcription factor kappa-B (NF-kappa B) activation in the human myeloma cell line OH-2. Agonistic antibodies to either of the TNFRs were able to induce proliferation in OH-2 cells, while only antibodies to the p55 TNFR could activate the NF-kappa B. TNF was 100-1000-fold more potent than LT alpha in activation of NF-kappa B and in induction of proliferation in OH-2 cells. Only a 2-fold difference between TNF and LT alpha in affinity for the TNFRs was detected, indicating that the difference in the specific activities of the cytokines can not be explained by different binding affinities. Antagonistic mAbs to either the p55 or p75 TNFR blocked the binding of both cytokines to the cells and significantly inhibited proliferation induced by TNF. On the other hand, only the p55 TNFR mAb was capable of inhibiting the proliferative effect of LT alpha. The p55 mAb 44E potentiated the proliferation induced by LT alpha, but did not affect the TNF-mediated proliferation. The data lead to the following conclusions: (1) both TNFR species trigger proliferation of OH-2 cells, whereas only the p55 TNFR activates the NF-kappa B; (2) TNF signals through both TNFR, whereas LT alpha mediates its signal through the p55 TNFR only; (3) activation of the p55 TNFR by LT alpha is not optimal, but can be facilitated by co-stimulating the receptor with the mAb 44E.


Characterization of inflammatory cell infiltrate in human dental pulpitis.
To evaluate the microscopic characteristics and densities (per mm(2) ) of tryptase(+) mast cells, CD4(+) T helper lymphocytes, CD45RO(+) memory T lymphocytes, foxp3(+) T regulatory lymphocytes, CD20(+) B lymphocytes, CD68(+) macrophages, and CD31(+) blood vessels in human dental pulpitis (n=38) and healthy pulpal tissue (n=6). The pulps of 38 human teeth with a clinical diagnosis of irreversible pulpitis were removed by pulpectomy. The pulp tissue was immersed in 10% buffered formalin for evaluation using light microscopy. Tryptase, CD4, CD45RO, foxp3, CD20, CD68, and CD31 expressions were analysed using immunohistochemistry; other microscopic features, such as intensity of inflammatory infiltrate and collagen deposition, were evaluated using haematoxylin and eosin stain. Wilcoxon and Mann-Whitney tests were used for statistical analysis. The significance level was set at α=5%. Two microscopic patterns of pulpitis were found: group 1 (G1) (n=15) had an intense inflammatory infiltrate and mild collagen deposition; conversely, group 2 (G2) (n=23) had a scarce inflammatory infiltrate and intense collagen deposition. The numbers of CD68(+) macrophages (P=0.004) and CD20(+) B (P=0.068) lymphocytes and the density of blood vessels (P=0.002) were higher in G1 than in G2. However, a similar number of CD4(+) and CD45RO(+) T lymphocytes was found in both groups (P>0.05). When present, tryptase(+) mast cells were equally distributed in G1 and G2, whereas foxp3(+) T regulatory lymphocytes were detected in 59% and 14% of the samples of G1 and G2. Controls exhibited lower numbers of foxp3, tryptase, CD4, CD45RO, CD68 and CD20 positive cells than G1 and G2. Irreversible pulpitis had distinct microscopic features with important quantitative and qualitative differences in inflammatory cell infiltration.


Alginate Hydrogel-Embedded Capillary Sensor for Quantitative Immunoassay with Naked Eye.
We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. Through measuring the length of the liquid phase of the microfluidics in the capillary at a given time, the concentration of the ALP could be quantified with the naked eye. Since ALP is widely applied as a signal reporter for immunoassays, the AHCS could easily accommodate conventional immune sensing platforms. We justify the practicality of AHCS with hepatitis B virus surface antigen (HBsAg) in serum samples and got comparable results with commercialized immunoassay. This AHCS is easy to make and use, effective in cost, and robust in quantification with the naked eye, showing great promise for next generation point-of-care testing.


Continuous supplementary tactile feedback can be applied (and then removed) to enhance precision manipulation.
Human sensorimotor control of dexterous manipulation relies on afferent sensory signals. Explicit tactile feedback is generally not available to prosthetic hand users, who have to rely on incidental information sources to partly close the control loop, resulting in suboptimal performance and manipulation difficulty. Recent studies on non-invasive supplementary sensory feedback indicated that time-discrete vibrational feedback delivered upon relevant mechanical events outperforms continuous tactile feedback. However, we hypothesize that continuous tactile feedback can be more effective in non-routine manipulation tasks (i.e., tasks where the grip force is modified reactively in response to the sensory feedback due to the unpredictable behavior of the manipulated object, such as picking and holding a virtual fragile object) if delivered to highly sensitive areas. We further hypothesize that this continuous tactile feedback is not necessary during all the duration of the manipulation task, since adaptation occurs. We investigated the effectiveness of continuous tactile feedback in precision manipulation, together with a new sensory feedback policy, where the continuous tactile feedback is gradually removed when the grasp reaches a steady state (namely, transient tactile feedback). We carried out an experiment in a virtual-reality setting with custom tactile feedback devices, which can apply continuous pressure and vibrations, attached to the thumb and index finger. We enrolled 24 healthy participants and instructed them to pick and hold a fragile virtual cube without breaking it. We compared their manipulation performance when using four different sensory feedback methods, i.e., no tactile feedback, discrete vibrations, continuous tactile feedback, and transient tactile feedback. The latter consisted of gradually removing the continuous feedback in the static phase of the grasp. Continuous tactile feedback leads to a significantly larger number of successful trials than discrete vibrational cues and no feedback conditions, yet the gradual removal of the continuous feedback yields to comparable outcomes. Moreover, the participants preferred the continuous stimuli over the vibrational cues and the removal in the static phase did not significantly impact their appreciation of the continuous tactile feedback. These results advocate for the use of continuous supplementary tactile feedback for fine manipulation control and indicate that it can seamlessly be removed in the static phase of the grasp, possibly due to the mechanism of sensory adaptation. This encourages the development of energy-efficient supplementary feedback devices for prosthetic and telemanipulation applications, where encumbrance and power consumption are burdensome constraints.


Efficacy of treating segmental bone defects through endochondral ossification: 3D printed designs and bone metabolic activities.
Three-dimensional printing (3D printing) is a promising technique for producing scaffolds for bone tissue engineering applications. Porous scaffolds can be printed directly, and the design, shape and porosity can be controlled. 3D synthetic biodegradable polymeric scaffolds intended for in situ bone regeneration must meet stringent criteria, primarily appropriate mechanical properties, good 3D design, adequate biocompatibility and the ability to enhance bone formation. In this study, healing of critical-sized (5 mm) femur defects of rats was enhanced by implanting two different designs of 3D printed poly(l-lactide-co-ε-caprolactone) (poly(LA-co-CL)) scaffolds seeded with rat bone marrow mesenchymal stem cells (rBMSC), which had been pre-differentiated in vitro into cartilage-forming chondrocytes. Depending on the design, the scaffolds had an interconnected porous structure of 300-500 μm and porosity of 50-65%. According to a computational simulation, the internal force distribution was consistent with scaffold designs and comparable between the two designs. Moreover, the defects treated with 3D-printed scaffolds seeded with chondrocyte-like cells exhibited significantly increased bone formation up to 15 weeks compared with empty defects. In all experimental animals, bone metabolic activity was monitored by positron emission tomography 1, 3, 5, 7, 11 and 14 weeks after surgery. This demonstrated a time-dependent relationship between scaffold design and metabolic activity. This confirmed that successful regeneration was highly reproducible. The in vitro and in vivo data indicated that the experimental setups had promising outcomes and could facilitate new bone formation through endochondral ossification.


An EPR method for estimating activity of antioxidants in mouse skin using an anthralin-derived radical model.
Inhibitory effects of intravenously or orally administered antioxidants on the anthralin-derived radical generated in skin (mainly in the epidermis) of living mice by ultraviolet-A (UVA) irradiation were estimated. Anthralin was applied to the dorsal skin of living mice and the mice were then exposed to UVA. The EPR signal intensity in skin tissue strips obtained from mice after anthralin-UVA treatment was measured by an X-band EPR spectrometer. Several common antioxidants such as ascorbate, glutathione and Trolox (a vitamin E analogue) intravenously administered to mice reduced anthralin-derived radical generation. Trolox showed the most prolonged and powerful effect. Intravenous injection of a clinically used cerebral neuroprotective drug, Edarabone (Radicut), also showed depletion for the anthralin-derived radical. Oral administration of a commercialized nutritional supplement (a cocktail of 17 herbals and vitamins) also attenuated the anthralin-derived radical. The anthralin-UVA treatment model for antioxidant activity in the epidermis is a potentially feasible method to estimate activity of antioxidants in the body.


Evolution from possible primitive tRNA-viroids to early poly-tRNA-derived mRNAs: a new approach from the poly-tRNA theory.
Poly-tRNA theory have revealed that the tRNA gene-clusters in the Bacillus subtilis trrnD- and rrnB-operons are relics of early peptide-synthesizing RNA apparatus. The trrnD-type and rrnB-type poly-tRNA models were re-analyzed by using recent databases. The results elucidated that the 16 amino acid (aa)-trrnD- and the 21 aa-rrnB-peptides (whose aa sequences are in the order of aa specificities of tRNAs in the respective tRNA cluster) are really relics of earliest peptides encoded by most primitive mRNAs, trrnD-mRNA and rrnB-mRNA, which are homologous to tRNA(Gly) and tRNA(His), respectively. Genes encoding various protein superfamilies (including pgtB protein, glycyl-tRNA synthetase alpha, C-type lectin, F1-ATP-synthase gamma, etc) were concluded to have derived from tRNA(Gly)-tRNA(Cys)-tRNA(Leu) region (including trrnD-mRNA region) in the trrnD-poly-tRNA. Genes for another group of protein superfamilies (including adenylate kinase, glyceraldehyde-3-phosphate dehydrogenase, helix-turn-helix DNA-binding domains, etc.) were found to have derived rrnB-mRNA, which is most plausibly homologous to a region containing the tRNA(His) of the rrnB-poly-tRNA. Thus Proto-tRNA((Gly)) reconstructed from tRNA(Gly) and other tRNAs strongly suggested that proto-tRNA was most plausibly a viroid-like possibly self-cleavable replicable ribozyme possessing a possible hammerhead-like structure.


In vitro evaluation of antiproliferative potential of topical cyclooxygenase inhibitors in human Tenon's fibroblasts.
Pharmacologic agents which inhibit fibroblast proliferation and scar formation may improve the success of glaucoma filtration surgery. To evaluate the potential use of nonsteroidal anti-inflammatory drugs as an antifibrotic treatment following glaucoma filtration surgery, the time and dose-related effects of four commonly used topical cyclo-oxygenase inhibitors--diclofenac, flurbiprofen, piroxicam, and suprofen--on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of a drug and analysed for dose response 1, 3, and 8 days following drug addition. The cell density was quantified by Coulter counting, hexosaminidase assay, and [3H]thymidine uptake into the DNA. All four drugs inhibited fibroblast attachment at the highest concentrations. Diclofenac was the most effective agent in inhibiting fibroblast proliferation, with inhibition occurring at a range of concentrations above 10(-3)-10(-4) mmol l-1. Flurbiprofen, piroxicam, and suprofen were comparable to each other in their antiproliferative activities, with inhibition occurring at a range of concentrations above 10(-1)-10(-2) mmol l-1. These results suggest a potential role for the commonly used topical nonsteroidal anti-inflammatory drugs in preventing excessive fibroblast proliferation following GFS, but further clinical studies are indicated to assess their activity as anti-inflammatory and antiproliferative agents in preventing bleb failure.


Oswaldo Gonçalves Cruz: the character, the scientist, the academician.
The present work analyses some particular aspects of Oswaldo Cruz's unique biography, valuing his work, which was built along a successful physician and scientist professional trajectory and also as a courageous and fortunate formulator of public health policies and of fight strategies against the epidemics that seasonally affected the city of Rio de Janeiro at the beginning of the 20th century. The authors also dwell on his legacy as Head scientist and manager of the Institute that bears his name and became the template for experimental research and medicine in Brazil and the bedrock of the Fundação Oswaldo Cruz, one of the most important Brazilian Institutions devoted to teaching, research, development and production in health. This heritage made possible to overcome the existing dissensions between doctors and scientists to build a sanitary movement committed to the major health problems in Brazil. Finally, the paper explores some features of the character and reports some of his moments during his passage, as a Full Academician, at the Brazilian Academia Nacional de Medicina.


Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State.
The rate of glycolytic metabolism changes during differentiation of human embryonic stem cells (hESCs) and reprogramming of somatic cells to pluripotency. However, the functional contribution of glycolytic metabolism to the pluripotent state is unclear. Here we show that naive hESCs exhibit increased glycolytic flux, MYC transcriptional activity, and nuclear N-MYC localization relative to primed hESCs. This status is consistent with the inner cell mass of human blastocysts, where MYC transcriptional activity is higher than in primed hESCs and nuclear N-MYC levels are elevated. Reduction of glycolysis decreases self-renewal of naive hESCs and feeder-free primed hESCs, but not primed hESCs grown in feeder-supported conditions. Reduction of glycolysis in feeder-free primed hESCs also enhances neural specification. These findings reveal associations between glycolytic metabolism and human naive pluripotency and differences in the metabolism of feeder-/feeder-free cultured hESCs. They may also suggest methods for regulating self-renewal and initial cell fate specification of hESCs.


The DEBR rat: an animal model of human alopecia areata.
The Dundee experimental bald rat (DEBR) is reported as a model for human alopecia areata. Parallels with human alopecia areata were observed in relation to the gradual and patchy loss of hair and the penetration of both pelage and vibrissa follicles by mononuclear cells. In particular, the apparent disruption of the follicles within the precortical region of the epidermal component and consequent alterations of normal geometrical relationships between dermal and epidermal components relate directly to similar studies on human alopecia areata. In comparison with other previously described hypotrichotic rodent mutants, the DEBR rat exhibits a unique mechanism of hair loss which may provide important information regarding the pathomechanism of human alopecia areata.


The effects of neuroticism, extraversion, and positive and negative life events on a one-year course of depressive symptoms in euthymic previously depressed patients versus healthy controls.
We investigated a) the concurrent impact of positive and negative life events on the course of depressive symptoms in persons remitted from depression and healthy controls, b) whether the impact of life events on symptom course is moderated by the history of depression and the personality traits of neuroticism and extraversion, and c) whether life events mediate possible relationships of history of depression and personality traits with symptom course. Using data from the Netherlands Study of Depression and Anxiety, we examined 239 euthymic participants with a previous depressive disorder based on DSM-IV and 450 healthy controls who completed a) baseline assessments of personality dimensions (NEO Five-Factor Inventory) and depression severity (Inventory of Depressive Symptoms [IDS]) and b) 1-year follow-up assessments of depression severity and the occurrence of positive and negative life events during the follow-up period (List of Threatening Events Questionnaire). Remitted persons reported higher IDS scores at 1-year follow-up than did the controls. Extraversion and positive and negative life events independently predicted the course of depressive symptoms. The impact of life events on symptom course was not moderated by history of depression or personality traits. The effect of extraversion on symptom course was partly caused by differential engagement in positive life events.


Actions of genistein on contractile response of smooth muscle isolated from guinea pig gallbladder.
Defective contractile motility of the gallbladder is an important factor for gallstone formation. Estrogen might increase the risk of gallstones and cholecystitis, and estradiol inhibits the contractile activity of isolated strips of guinea pig gallbladder. The potential risks associated with hormone replacement therapy (HRT) include symptomatic gallstones. Phytoestrogen have been used to treat menopause syndromes by replacing traditional estrogen. This experiment aimed to determine the effects of the phytoestrogen genistein on the contractile response of smooth muscle strips isolated from guinea pig gallbladder and its possible mechanism of action. Guinea pigs were sacrificed to remove the whole gallbladder. Two or three smooth muscle strips were cut longitudinally. Each strip was suspended in a tissue chamber containing Krebs solution. After 2 hours of equilibration, contractile response indexes were recorded. Different concentrations of genistein were added to the chamber and the contractile responses were measured. Each antagonist was added 2 minutes before genistein to study possible mechanisms. The effect of genistein on calcium-dependent contraction curves and biphasic contraction in calcium-free Krebs solution were measured. Genistein decreased the resting tension dose-dependently, and reduced the mean contractile amplitude and frequency in gallbladder strips. Ranitidine partly inhibited the effect of genistein, but methylene blue, Nomega-nitro-L-arginine, and propranolol hydrochloride did not influence this action. Genistein had no significant effects on calcium-dependent contraction. Genistein reduced the first contraction induced by acetylcholine chloride, but did not affect the second contraction caused by CaCl2. Genistein relaxed smooth muscle isolated from the gallbladder of guinea pigs and this might contribute to the formation of gallstones. The inhibitory action might be related to H2 receptors and the release of intracellular Ca2+ from sarcoplasmic reticulum. Replacing traditional estrogen with phytoestrogen to treat menopause syndromes may increase the risk of gallstone formation.


Paclobutrazol Inhibits Abscisic Acid Biosynthesis in Cercospora rosicola.
Three plant growth regulators, paclobutrazol, ancymidol, and decylimidazole, which are putative inhibitors of gibberellin (GA) biosynthesis, were studied to determine their effect on abscisic acid (ABA) biosynthesis in the fungus Cercospora rosicola. All three compounds inhibited ABA biosynthesis, and paclobutrazol was the most effective, inhibiting ABA 33% at 0.1 micromolar concentrations. In studies using (E,E,)-[1-(14)C] farnesyl pyrophosphate, it was shown that ancymidol blocked biosynthesis prior to farnesyl pyrophosphate (FPP), whereas paclobutrazol and decylimidazole acted after FPP. The three inhibitors did not prevent 4'-oxidation of (2Z,4E)-alpha-ionylideneacetic acid. C. rosiciola metabolized ancymidol by demethylation to alpha-cyclopropyl-alpha-(p-hydroxyphenyl)-5-pyrimidine methyl alcohol. Paclobutrazol was not metabolized by the fungus. Information that these plant growth regulators inhibit ABA as well as GA biosynthesis should prove useful in determining the full range of action of these compounds.


Use of Musculoskeletal Ultrasound and Regenerative Therapies in Soccer.
Improvements in ultrasound technology have increased the popularity and use of ultrasound as a diagnostic and therapeutic modality for many soccer-related musculoskeletal (MSK) injuries. As a dynamic imaging modality, ultrasound offers increased accuracy and efficacy with minimally invasive procedures, such as guided injections, percutaneous tenotomy, and regenerative therapies, in the clinical setting. Emerging evidence indicates that regenerative therapies, such as platelet-rich-plasma (PRP), mesenchymal stem cells, and amniotic products, are a promising treatment for many MSK injuries and are gaining popularity among professional athletes. PRP is a safe treatment for a number of MSK conditions and has been included in the standard of care. However, conflicting evidence on return-to-play timeframes and efficacy in certain MSK conditions have led to inconsistent recommendations on indications for use, dose, and timing of treatment. Mesenchymal stem cell therapy, while promising, lacks high-level evidence of efficacy despite its increasing use among athletes. Currently, no data are available regarding the outcome of the use of amniotic products for the treatment of injuries in athletes. Furthermore, preparation of many regenerative therapies eclipses the concept of minimal manipulation and is subject to US Food and Drug Administration phase I to III trials. High-level research on regenerative medicine therapies should be continuously conducted to establish their clinical efficacy and safety data.


Phylogenetic comparison of rabies viruses from disease outbreaks on the Svalbard Islands.
Periodic wildlife rabies epizootics occur in Arctic regions. The original sources of these outbreaks are rarely identified. In 1980, a wildlife epizootic of rabies occurred on the previously rabies-free Svalbard Islands, Norway. After this outbreak of rabies in the arctic fox population (Alopex lagopus), only single cases have been reported from the Islands over the following two decades. Phylogenetic characterization of four viruses isolated from infected arctic foxes from Svalbard from three different time periods suggest that the source of these epizootics could have been migration of this species from the Russian mainland. Arctic fox migration has likely contributed to the establishment of another zoonotic disease, Echinococcus multilocularis, on Svalbard in recent years.


Differential diagnosis and management of a patient with peripheral vestibular and central nervous system disorders: a case study.
Clinical examination and management of patients with meningiomas is primarily dependent upon appropriate diagnosis of tumor type and surgical intervention. Physical therapists should be able to identify patients presenting with signs and symptoms suggestive of potential central nervous system (CNS) disorders and refer the patient appropriately. In this case report, a 52-year-old female was referred to physical therapy after 18 months of unresolved dizziness. Oculomotor examination revealed evidence of peripheral vestibular and potential CNS disorders. The physical therapist referred the patient to a physician who ordered magnetic resonance imaging (MRI). The patient received five physical therapy sessions while waiting for the MRI which revealed a meningioma. The meningioma was surgically removed and the patient was subsequently relieved of all symptoms. Despite the presence of the meningioma, the patient reported improved stability during work-related activities and decreased dizziness as a result of physical therapy intervention pre-operatively. This case report emphasizes the importance of a physical therapists ability to perform and interpret an oculomotor examination in a patient presenting with signs consistent with peripheral vestibular and CNS disorders. It also demonstrates the role of physical therapy in collaboration with physicians in order to provide appropriate patient care management.


ZIF-8 Membranes via Interfacial Microfluidic Processing in Polymeric Hollow Fibers: Efficient Propylene Separation at Elevated Pressures.
Propylene/propane (C3H6/C3H8) separations are performed on a large scale by energy-intensive distillation processes. Membranes based on metal-organic framework (MOF) molecular sieves, such as zeolitic imidazolate framework-8 (ZIF-8), offer the potential to perform these separations at considerably lower cost. However, the fabrication of scalable ZIF-8 membranes with high performance at elevated pressures and temperatures is challenging. We report the fabrication of high-quality ZIF-8 hollow fiber membranes in engineered polymeric hollow fibers via the interfacial microfluidic membrane processing (IMMP) technique. Control of fiber microstructure, as well as optimization of IMMP conditions, allow us to achieve a C3H6/C3H8 separation factor of 180 (at 1 bar and 25 °C), which remains high (60) at 120 °C. Furthermore, high-pressure operation of these membranes was investigated. Detailed permeation measurements indicate excellent suppression of defects at higher pressures up to 9.5 bar, allowing a C3H6/C3H8 separation factor of 90 at 9.5 bar. The membranes also display a 4-fold increase in flux at 9.5 bar as compared to operation at 1 bar. The long-term stability of the ZIF-8 hollow fiber membranes is demonstrated by continuous operation over a month without loss of C3H6 permeance or selectivity.


Dichlorido{N'-[(pyridin-2-yl)methyl-idene-κN]acetohydrazide-κN',O}copper(II).
In the title compound, [CuCl(2)(C(8)H(9)N(3)O)], the Cu(II) atom has a distorted square-pyramidal CuCl(2)N(2)O coordination geometry. The tridentate acetohydrazide ligand occupies three basal positions, the fourth basal position being defined by a chloride anion at a distance of 2.2116 (6) Å. The second chloride anion is in the apical position and forms a longer Cu-Cl distance of 2.4655 (7) Å. Inter-molecular N-H⋯Cl hydrogen bonds are present in the crystal, leading to the formation of chains along [10[Formula: see text]].