Risk factors for unrecognized invasive carcinoma in patients with vulvar high-grade squamous intraepithelial lesion at vulvoscopy-directed biopsy.
To evaluate the prevalence and risk factors for unrecognized invasive carcinoma in a series of patients undergoing surgical excision after an office biopsy of vulvar high-grade squamous intraepithelial lesion (VHSIL). Two hundred and sixteen consecutive patients treated in a tertiary-level referral center for vulvar disease in north-western Italy were recruited. Patients' records were reviewed by trained personnel. Factors showing a statistically significant (p<0.05) association with detection of stromal invasion at excisional surgery in univariate analysis were further examined in a backward stepwise multiple logistic regression model. The median patient age was 50 years (range, 19-88). More than 25% patients with VHSIL at biopsy had associated cervical/vaginal intraepithelial neoplasia, and more than 35% had a multifocal lesion. Invasive carcinoma was detected in surgical specimens from 24 patients (11%). The depth of stromal invasion varied between 0.1 mm and 3.0 mm with a median of 0.5 mm. In multivariate analysis, the risk of invasive carcinoma detection was greater for patients in the highest tertile of age (p=0.008), for patients with a lesion ≥20 mm in size (p=0.013) and with clitoral involvement (p<0.001), and for patients presenting with a nodular lesion (p=0.078). Our study suggests that patient age, lesion size, clitoral involvement and nodular appearance in patients with VHSIL at vulvoscopy-directed biopsy are independently associated with the risk of unrecognized invasive carcinoma.


Leisure participation-preference congruence of children with cerebral palsy: a Children's Assessment of Participation and Enjoyment International Network descriptive study.
To examine participation-preference congruence, regional differences in participation-preference congruence, and predictors of whether children with cerebral palsy participate in preferred activities. The sample (n=236) included 148 males and 88 females aged 10 to 13 years, living in Victoria, Australia (n=110), Ontario (n=80), or Quebec (n=46), Canada. Ninety-nine (41.9%) were classed at Gross Motor Function Classification System (GMFCS) level I; 89 (37.7%) at GMFCS level II/III; and 48 (20.3%) at GMFCS level IV/V. Participants completed the Children's Assessment of Participation and Enjoyment and Preferences for Activity of Children questionnaires. Regional comparisons were performed using one-way analyses of variance and factors influencing participation-preference congruence were explored using multiple linear regression. The proportion of children doing non-preferred activities in each activity type was generally low (2-17%), with only one regional difference. Higher proportions were not doing preferred active physical (range 23.2-29.1% across regions), skill-based (range 21.7-27.9% across regions), and social activities (range 12.8-14.5% across regions). GMFCS level was the most important predictor associated with not doing preferred activities. Children with cerebral palsy did not always participate in preferred active physical and skill-based activities. Understanding discrepancies between preferences and actual involvement may allow families and rehabilitation professionals to address participation barriers.


Concepts for the rational selection of assays to be used in monitoring therapeutic drugs.
As the domain of monitoring therapeutic drugs rapidly expands from experimental investigations to everyday patient care, all clinical laboratory scientists, but especially clinical chemists, must learn to deal with their involvement in this expansion. First, the theoretical concepts underlying clinical pharmacology must be appreciated so that the laboratory's participation in it can succeed. Individual differences cause unpredictable variations of response to the customarily standardized drug dosage. Properly used, assays of drugs in blood can eliminate such variabilities. Second, the practical selection of which drug assays a laboratory intends to provide must be based on a rational evaluation of assay usefulness, integrating both clinical and laboratory considerations. Such a decision model is suggested; it is generally applicable in allocating priorities among an ever-increasing number of proposed tests under the constraint of finite resources.


The structural and spectroscopic characterisation of three actinyl complexes with coordinated and uncoordinated perrhenate: [UO2(ReO4)2(TPPO)3], [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2 and [NpO2(TPPO)4][ReO4].
The first structural characterization of an actinide complex with coordinated perrhenate is reported, [UO2(ReO4)2(TPPO)3] (1). In this [UO2]2+ complex two [ReO4]- anions and three TPPO (triphenylphosphine oxide) P=O donor ligands are coordinated in the equatorial plane in a cisoid arrangement. This bonding arrangement, and apparent strain observed in the equatorially bonded ligands, is attributed to the solid state packing in adjacent molecules in which hydrophobic TPPO ligands form an effective "shell" around a hydrophilic core of two UO2(ReO4)2 moieties. Solid state vibrational spectroscopy (infrared and Raman), 31P CP MAS NMR and elemental analysis are also consistent with the formula of 1. Solution state vibrational spectroscopy and 31P NMR measurements in EtOH indicate the lability of the TPPO and [ReO4]- groups. The photolytic generation of peroxide in EtOH solutions of 1 leads to the formation of trace quantities of [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2, 2, in which the coordinated [ReO4]- groups of 1 have been displaced by bridging O2(2-), derived from atmospheric O2. Finally, attempts to synthesise a [NpO2]+ analogue of have resulted only in the formation of [NpO2(TPPO)4][ReO4], 3, in which [ReO4]- acts solely as a counter anion. From these results it can be concluded that [ReO4]- will bond to [UO2]2+, but will be readily displaced by a more strongly coordinating ligand (e.g. peroxide) and will not coordinate to an actinyl cation with a lower charge, [NpO2]+, under the same reaction conditions.


Switchable DNA-Encoded Chemical Library: Interconversion between Double- and Single-Stranded DNA Formats.
DNA-encoded chemical libraries (DEL) have attracted substantial attention due to the infinite possibility for hit discovery in both pharmaceutical companies and academia. The encoding method is the initial step of DEL construction and one of the cornerstones of DEL applications. Classified by the DNA format, the existing DEL encoding strategies were categorized into single-stranded DNA-based strategies and double-stranded DNA-based strategies. The two DEL formats have their unique advantages but are usually incompatible with each other. To address this issue, we propose the concept of interconversion between double- and single-stranded DEL based on the "reversible covalent headpiece (RCHP)" design, which combines maximum robustness of synthesis with extraordinary flexibility of applications in distinct setups. Future opportunities in this field are also proposed to advance DEL technology to a comprehensive drug discovery platform.


Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1-Generation Mice.
Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F1 generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose-related manners on postnatal days (PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose-related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p = 0.0209) in the high-dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose-related manner (p < 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose-related manner (p < 0.01), and for female offspring it was delayed significantly in the high-dose group (p < 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose-related manner (p < 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high-dose group in the F1 generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice.


Health-promoting prisons in the female estate: an analysis of prison inspection data.
Women in prison have comparatively greater health needs than men, often compounded by structures and policies within the prison system. The notion of a 'health-promoting' prison is a concept which has been put forward to address health inequalities and health deterioration in prisons. It has, however, not been fully discussed in relation to women in prison. The paper aims to distil the learning and evidence in relation to health promotion in female prisons using prison inspection reports of women's prisons in England and Wales. Prison inspection reports are one way of ascertaining the contemporary situation in prisons. Prison inspections are often unannounced and use a myriad of methods to draw conclusions around various aspects of prison life. Thirteen prison inspection reports were analysed thematically focusing on health promotion within the institutions. Two analysts conducted the work using NVivo 12. Five core thematic areas were identified during the analysis of the reports. Saliently, a joined-up approach to health promotion was not a common feature in the prisons and indeed the focus tended to be on screening and 'lifestyle issues' rather than a concern for the underlying determinants of health. There was often an absence of a strategic approach to health promotion. There were some good examples of the democratic inclusion of women in prison in shaping services, but this was not widespread and often tokenistic. There were some examples of inequity and the inspection reports from a small number of institutions, illustrated that the health needs of some women remained unmet. The paper suggests that there is potentially some work before conditions in women's prisons could be described as 'health-promoting', although there are some examples of individual prisons demonstrating good practice. The health promoting prison movement has, implicitly at least, focused on the needs of men in prison and this has been to the exclusion of the female prison population. This does lead to several challenges and the potential for exacerbating health challenges faced by an already marginalised and vulnerable group. Greater focus on the health promotion needs of women in prison is required.


[Regulatory lymphocytes: a new cooperation between T and B cells for a better control of the immune response].
Mechanims of peripheral tolerance include molecular controls and the presence of regulatory lymphocytes. Regulatory T lymphocytes (Tregs) correspond to different sub-populations of T cells that control immune responses due to the production of cytokines, such as IL-10 and with direct cell-to-cell contacts. Tregs targets are antigen presenting cells, such as dendritic cells, effector CD4(+) and CD8(+) lymphocytes but also effector antibody-producing B lymphocytes. Regulatory B lymphocytes (Bregs) have been more recently described and likely represent different sub-populations of B cells that control the development of autoimmune and inflammatory diseases due to the production of IL-10 and using intercellular contacts. Bregs targets encompass all the cells involved in the immune responses which are thus under a dual control by regulatory lymphocytes. Development and efficient activity of Tregs appear dependent of Bregs for a better regulation of autoimmune reactions, of anti-infectious reactions, but also of anti-tumor reactions.


Minimization of door-to-balloon time for ST-elevation acute myocardial infarction: a case report.
It is of utmost importance to minimize the door-to-balloon time for the initial treatment of ST-elevation acute myocardial infarction. In this case report, we made all kinds of efforts to minimize procedures in the emergency department (ED minimization) as well as in the catheter laboratory without sacrificing safety.


Identification of Four ATP-Binding Cassette Transporter Genes in Cnaphalocrocis medinalis and Their Expression in Response to Insecticide Treatment.
The ATP-binding cassette (ABC) transporters belong to a superfamily of genes involved in the transport of specific molecules across lipid membranes, as well as insecticide resistance, present in all living organisms. In this study, we combined the Cnaphalocrocis medinals transcriptome database with a bioinformatics approach to identify four C. medinals ABCs (CmABCs), including CmABCG1, CmABCG4, CmABCC2 and CmABCC3. Tissue expression analysis showed that these genes had a tissue-specific expression pattern. CmABCG1 had significantly higher expression in the haemolymph and head compared to the other tissues. The expression of CmABCG4, CmABCC2 and CmABCC3 was highest in the midgut, followed by expression in the fat body. The developmental stage expression analysis showed that CmABCG1, CmABCG4, CmABCC2 and CmABCC3 were mainly expressed in adults. The transcription of CmABCG1, CmABCG4 and CmABCC2 was significantly induced by chlorpyrifos. Taken together, the results of our study provided useful information for understanding of the detoxification system of C. medinalis.


Complex patterns of linkage disequilibrium in the Huntington disease region.
The genetic defect causing Huntington disease (HD) has been mapped to 4p16.3 by linkage analysis using DNA markers. Two apparently contradictory classes of recombination events in HD kindreds preclude precise targeting of efforts to clone the disease gene. Here, we report a new recombination event that increases support for an internal candidate region of 2.5 Mb between D4S10 and D4S168. Analysis of 23 DNA polymorphisms in 4p16.3 revealed a complex pattern of association with the disease gene that failed to narrow the size of the candidate region. The degree of linkage disequilibrium did not show a continuous increase across the physical map, nor was a region of extreme disequilibrium identified. Markers displaying no association with the disorder were interspersed with and, in many cases, close to markers displaying significant disequilibrium. Comparison of closely spaced marker pairs on normal and HD chromosomes, as well as analysis of haplotypes across the HD region, suggest that simple recombination subsequent to a single original HD mutation cannot easily explain the pool of HD chromosomes seen today. A number of different mechanisms could contribute to the diversity of haplotypes observed on HD chromosomes, but it is likely that there has been more than one and possibly several independent origins of the HD mutation.


Astroglial cells: glucocorticoid target cells in the brain.
Glutamine synthetase (GS), an enzyme localized in astroglial cells in the brain, is directly implicated in brain detoxification. An ontogenic study of GS activity was performed in homogenates from four distinct brain areas in comparison with the respective astrocytes obtained in primary cultures. GS was induced by hydrocortisone in the astrocytes of all brain areas studied; only cerebellum and cerebral hemisphere astroglial cells had a higher specific activity when compared with the corresponding homogenates. N6O2-Dibutyryl adenosine 3',5'-cyclic monophosphate (dBc AMP), insulin, soluble brain factors, and noradrenaline (NA) were also able to modulate GS activity. Brain factors as well as dBc AMP interfered with hydrocortisone induction of GS. Regulation by hydrocortisone paralleled the variation in its concentration in brain during development. We conclude that astroglial cells are target cells for glucocorticoids, which may modulate ammonia detoxification in these cells.


[Who were the patients under Charcot's care at the Salpêtrière?].
The answer to the question: who were the patients in Charcot's wards in the Salpêtrière Hospital, raises the major problem of the orientation of his researches: diseases of old people, internal pathology, diseases of the nervous system.


Homologues of murine Vh11 gene are conserved during evolution.
Since the murine Vh11 gene family shows 75% homology with group III VH gene families and is preferentially expressed in B-1 lymphocytes, we have analyzed if corresponding Vh11 genes existed across phylogenetically distant mammalian lineages. In a Southern blot, homologues of the murine Vh11 gene were detected in the genomic DNA from rats, pigs, sheep, cattle, horses, dogs and man. These observations suggest conservation of corresponding sequences of the Vh11 gene family during evolution, similar to group III VH genes, either because of strong selection pressures essential for species fitness and survival or molecular drive leading to these consequences.


Treatment. Corticosteroids and anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs and corticosteroids are important elements in the therapeutic armamentarium for patients with systemic lupus. The choice of NSAID needs to be individualized, but with optimal usage NSAIDs can often be used to manage symptoms previously treated with corticosteroids. For serious disease manifestations, corticosteroids are the cornerstone of therapy. Maximization of clinical response and avoidance of side effects continue to be important management goals. Different dosage regimens, such as intravenous methylprednisolone pulse therapy, and adjunctive agents, such as cyclophosphamide, are of continued interest in severe and potentially life-threatening disease. In addition, new nonsteroidal anti-inflammatory strategies including omega-3 series eicosanoids and new steroidal strategies including deflazacort and anti-glucocorticoids hold promise for continued improvement in the treatment on systemic lupus.


Studies on the turnover of triglyceride and esterified cholesterol in subjects with the nephrotic syndrome.
Factors involved in the hyperlipidemia of nephrosis have been studied in seven patients. The turnover of triglyceride was measured in plasma very low density lipoproteins after the injection of glycerol-(14)C. The turnover of esterified cholesterol was measured in whole plasma and in very low density lipoproteins after the injection of mevalonic acid-2-(3)H. Urine protein loss was found to be significantly correlated with the plasma concentrations of triglyceride and free cholesterol, suggesting that increasing loss of protein is associated with the formation of larger lipoproteins. Lactescent plasmas were found in the subjects with the greatest protein loss. The turnover rate of triglyceride tended to be higher among subjects with higher than with lower triglyceride concentrations and was on the average higher than among six normotriglyceridemic subjects. However, there was also evidence for decreased clearance of glyceride from plasma. The hypertriglyceridemia of nephrosis appeared to reflect both increased formation of glyceride and decreased removal of glyceride from plasma. The turnover of esterified cholesterol was significantly higher in whole plasma of nephrotic subjects than in normocholesterolemic nonnephrotic patients. Esterified cholesterol turnover in very low density lipoproteins was raised in the two subjects in whom a major part of total esterified cholesterol was carried in this lipoprotein fraction. These studies were repeated in one subject after remission was induced. The cessation of urinary loss of protein was associated with reductions in the concentrations and turnover of triglyceride and esterified cholesterol. The increased turnover of plasma lipids in nephrosis may reflect the general increase in the formation of protein.


Role for DNA methylation in the control of cell type specific maspin expression.
The nucleotide 5-methylcytosine is involved in processes crucial in mammalian development, such as X-chromosome inactivation and gene imprinting. In addition, cytosine methylation has long been speculated to be involved in the establishment and maintenance of cell type specific expression of developmentally regulated genes; however, it has been difficult to identify clear examples of such genes, particularly in humans. Here we provide evidence that cytosine methylation of the maspin gene (SERPINB5) promoter controls, in part, normal cell type specific SERPINB5 expression. In normal cells expressing SERPINB5, the SERPINB5 promoter is unmethylated and the promoter region has acetylated histones and an accessible chromatin structure. By contrast, normal cells that do not express SERPINB5 have a completely methylated SERPINB5 promoter with hypoacetylated histones, an inaccessible chromatin structure and a transcriptional repression that is relieved by inhibition of DNA methylation. These findings indicate that cytosine methylation is important in the establishment and maintenance of cell type restricted gene expression.


The regulation of host cellular and gut microbial metabolism in the development and prevention of colorectal cancer.
Metabolism regulation is crucial in colorectal cancer (CRC) and has emerged as a remarkable field currently. The cellular metabolism of glucose, amino acids and lipids in CRC are all reprogrammed. Each of them changes tumour microenvironment, modulates bacterial composition and activity, and eventually promotes CRC development. Metabolites such as short chain fatty acids, secondary bile acids, N-nitroso compounds, hydrogen sulphide, polyphenols and toxins like fragilysin, FadA, cytolethal distending toxin and colibactin play a dual role in CRC. The relationship of gut microbe-metabolite is essential in remodelling intestinal microbial ecology composition and metabolic activity. It regulates the metabolism of colonic epithelial cells and changes the tumour microenvironment in CRC. Microbial metabolism manipulation has been considered to be potentially preventive in CRC, but more large-scale clinical trials are required before their application in clinical practice in the near future.


A method for the separation of peptides and alpha-amino acids.
1. Peptides and alpha-amino acids, occurring in mixtures from various sources, can be separated into one fraction containing the amino acids and several peptide fractions. This is achieved by chelation of the mixture with Cu(2+) ions and subsequent chromatography of these chelates over the acetate form of diethylaminoethylcellulose or triethylaminoethylcellulose. 2. The amino acid fraction is obtained by elution with 0.01m-collidine-acetate buffer, pH8.0. 3. Peptide fractions are eluted with 0.01m-collidine-acetate buffer, pH4.5, 0.17n-acetic acid and 0.1n-hydrochloric acid respectively. 4. With the exception of aspartic acid and glutamic acid, which are partly found in the acidic peptide fraction, the amino acids are completely separated from the peptides. 5. Contamination of the acidic peptide fraction with glutamic acid and aspartic acid can be largely avoided by previous addition of an excess of arginine. 6. Copper is removed from the eluates by extraction with 8-hydroxyquinoline in chloroform.


First trimester diagnosis of fetal nuchal edema. Report of 29 cases.
During a 4-year period, 29 fetal nuchal edemas were observed, associated with other ultrasound abnormalities in 7 cases (24%). Fetal karyotypes were abnormal in 10 cases: 6 trisomy 21; 3 trisomy 18, and 1 Turner's syndrome. Isolated fetal nuchal edema was associated with aneuploidy in 4 cases: 3 trisomy 21, and 1 trisomy 18. The average age of the women carrying a fetus with nuchal edema associated or not with a trisomy 21 was 38.3 and 30.8 years, respectively. These results are similar to those found in the literature. It would appear that maternal age is a better marker in trisomy 21 screening than isolated fetal nuchal edema.


Symptomatic Celiomesenteric Trunk: Variable Presentations and Outcomes in 2 Patients.
Mesenteric ischemia can be difficult to diagnose without a high degree of suspicion because it presents in a variety of ways. Visceral vascular collaterals between the fore- and midgut often provide protection against ischemia; however, the presence of anatomic variations, such as celiomesenteric trunk, can undermine the expected redundancy. Misdiagnosis can result in prolonged suffering or death, as evidenced in 2 of our patients with celiomesenteric trunk. The first patient with chronic mesenteric ischemia was diagnosed in the clinic and underwent successful surgical correction; the other had overwhelming, acute mesenteric ischemia, which resulted in death. Our cases show that successful diagnosis and management of mesenteric ischemia require astute interpretation of radiologic images.


The effects of oral digoxin therapy in primary mitral leaflet prolapse.
The effects of oral digoxin on symptoms, arrhythmias, exercise tolerance and echocardiographic function in primary mitral leaflet prolapse were studied in 23 patients using a double-blind crossover protocol. Digoxin reduced the incidence and severity of chest pain compared with both the control (P = 0.0002) and placebo (P = 0.0005) periods. We found a high (83%) incidence of predominantly minor arrhythmias on continuous ambulatory monitoring. Digoxin favourably affected the incidence of frequent supraventricular ectopic beats and supraventricular tachycardia but was associated with a significant number (P less than 0.0025) of asymptomatic bradyarrhythmias. In patients with frequent ventricular ectopics, digoxin had no consistent effect. No difference in exercise tolerance between treatment periods was found on maximal treadmill stress testing, but digoxin administration resulted in an increase in echocardiographic mean circumferential fibre shortening velocity (P less than 0.01) and fractional shortening percent (P less than 0.01). This study demonstrates the efficacy of oral digoxin therapy in ameliorating chest pain in patients with primary mitral leaflet prolapse and suggests a favourable effect on supraventricular arrhythmias in such patients.


Development of a protocol for allogeneic marrow transplantation for severe systemic sclerosis: paradigm for autoimmune disease.
Some types of severe autoimmune disease are associated with significant morbidity and a high mortality rate. Many of these cases occur in young adults who, even if they survive, become severely debilitated. Systemic sclerosis (SSc) is a paradigm for other severe autoimmune diseases in which patients with poor prognostic features can be identified early in the course of the disease. Allogeneic marrow transplantation may be effective for the control of autoimmune diseases like SSc because the preparative regimen will significantly suppress the host immune system and the antihost effects of the donor immune system in the engrafted marrow will help maintain the suppression of the host immune system. Considering the morbidity and poor prognosis associated with severe SSc and the favorable outcome now associated with allogeneic marrow transplantation from HLA identical siblings for other nonmalignant diseases, Phase I and II studies are warranted. These will evaluate the safety of allogeneic marrow transplantation and explore its role in the management and control of a severe autoimmune disease. We review issues important in the development of an allogeneic marrow transplant protocol for severe SSc, including patient selection, plan of treatment, prevention of graft versus host disease, supportive care, and evaluation after transplant.


Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on sleep-related postural mechanisms.
Experimental and clinical evidences indicate that endocrine mechanisms, particularly involving the pineal gland, exert a role in the development of postural deficits leading to the occurrence of idiopatic scoliosis (IS). In particular, experiments performed in bipedal animals have shown that removal of the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in such preparations, administration of this hormone prevented the development of this deformity (cf. 131). It appears also that adolescents with IS showed a reduced level of serum M with respect to age-related control subjects. The possible mechanisms involved in the M regulation of the tonic contraction of the axial musculature have been discussed. It is known that the pineal gland is implicated in the control of circadian rhythms, including the sleep-waking cycle, and that during this cycle there are prominent changes in postural activity, which affect not only the limbs, but also the axial musculature. These changes are characterized by a decrease followed by a suppression of postural activity, which occur particularly during transition from wakefulness to synchronized sleep and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural atonia may also occur during the cataplectic episodes, which are typical of narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system, intervene in the suppression of posture during REM sleep, as well as during the cataplectic episodes which occur in narcolepsy. These structures are under the modulatory (inhibitory) influence of the dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located. We postulated that M may act not only on the circadian pacemaker, but also directly on the pontine tegmental structures involved in the regulation of posture during the animal states indicated above. This hypothesis is supported by the facts that: 1) the dorsal pRF may contain specific binding sites for M; 2) this structure is particularly sensitive to M in adolescents, as well as in adult subjects affected by narcoleptic disturbances leading to cataplexy; 3) M increases the release of serotonin (5-HT), a neurotransmitter which enhances the postural tone by acting on the dorsal pRF: on the other hand, deficits in M levels may lower the activity of the serotoninergic raphe system, thus leading to a decrease or suppression of postural activity similar to that occurring either during REM sleep or during the cataplectic episodes typical of narcoleptic patients; 4) IS patients may show episodes of sleep apnea, a phenomenon which has been attibuted to a reduced tonic contraction of primary and accessory respiratory muscles during REM, resulting from a reduced release of 5-HT at dorsal pontine level. It has been postulated that, if the reduced M and 5-HT levels are subliminal to produce a complete suppression of posture under the conditions reported above, the reduced postural tone, which results from this condition may lead to the development of IS, due to hypotonia which affects the axial musculature. M secretion could be regulated not only by the activity of the serotoninergic raphe neurons projecting to the pineal gland, but probably also by the activity of noradrenergic LC neurons. It is likely that the development of IS, which results from a reduced level of M and 5-HT, may occur provided that the noradrenergic LC inhibition of the pontine structures is impaired. Such impairment could depend upon genetic factors, similar to those postulated to play a role in narcolepsy. In conclusion, the possibility exists that an impaired activity of brain monoaminergic systems may lead to disfunction in the production of M, which is apparently an important factor in the etiopathogenesis of IS.


Measuring conversations after acquired brain injury in 30 minutes or less: a comparison of two pragmatic rating scales.
Primary objective: This study compared the reliability, validity and feasibility of the Pragmatics Rating Scale (PRS) to the Profile of Pragmatic Impairment in Communication (PPIC). It was hypothesized that the PRS would have equivalent reliability and validity and superior feasibility. Research design: A correlational pilot study design was implemented. Methods and procedures: Participants were 15 adults with a history of ABI, who provided two conversation samples each, and 15 adults with no history of ABI, who provided one conversation sample each. Two clinicians used the PRS and PPIC to rate each conversation sample. Main outcomes and results: The results of the PRS showed good discriminative validity between the ABI and non-ABI group, adequate construct validity with the PPIC and the La Trobe Communication Questionnaire, superior interrater reliability to the PPIC, and good test-retest reliability. Also, the PRS demonstrated higher clinical feasibility than the PPIC as measured by mean completion time per sample and ratings on a clinical feasibility survey. Conclusions: These results supported our hypotheses that the PRS is sensitive to aspects of social communication often impaired by ABI, without the feasibility drawbacks of a more complex rating scale.


Hemodynamic profile of a new antihypertensive agent D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine (SK&F 92657).
The properties of a new antihypertensive agent, SK&F 92657, D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied. The compound, given intravenously, subcutaneously, or orally, caused a sustained fall in systemic blood pressure of conscious genetically hypertensive rats, normotensive cats, and renal hypertensive dogs. The fall in blood pressure of genetically hypertensive rats was maintained during 52 days of chronic dosing with no development of tolerance. The hemodynamic effects and mechanism of action of SK&F 92657 were investigated in anesthetized cats and dogs using a variety of techniques. Blood pressure was lowered by a direct vasodilator effect on precapillary blood vessels (arteries, arterioles), particularly in the renal, coronary, and skeletal muscle vasculatures, giving an overall decrease in total peripheral resistance with no significant change in cardiac output. In contrast, SK&F 92657 had no significant effect on capacitance blood vessel (veins, venules) tone or on vascular reactivity to vasoconstrictors and consequently did not cause postural hypotension. The beta-adrenoceptor-blocking actions of the drug prevented reflex increases in heart rate and cardiac output, except in the conscious dog, where vagal control of heart rate was predominant. It was also concluded that SK&F 92657 was not acting by alpha-adrenoceptor blockade, ganglion blockade, or inhibition of angiotensin II responses. A "central" action was unlikely, as SK&F 92657 caused vasodilatation in denervated autoperfused vascular beds.


Impact of hemodynamics on lumen boundary displacements in abdominal aortic aneurysms by means of dynamic computed tomography and computational fluid dynamics.
The aim of the present work is to quantitatively assess the three-dimensional distributions of the displacements experienced during the cardiac cycle by the luminal boundary of abdominal aortic aneurysm (AAA) and to correlate them with the local bulk hemodynamics. Ten patients were acquired by means of time resolved computed tomography, and each patient-specific vascular morphology was reconstructed for all available time frames. The AAA lumen boundary motion was tracked, and the lumen boundary displacements (LBD) computed for each time frame. The intra-aneurysm hemodynamic quantities, specifically wall shear stress (WSS), were evaluated with computational fluid dynamics simulations. Co-localization of LBD and WSS distributions was evaluated by means of Pearson correlation coefficient. A clear anisotropic distribution of LBD was evidenced in both space and time; a combination of AAA lumen boundary inward- and outward-directed motions was assessed. A co-localization between largest outward LBD and high WSS was demonstrated supporting the hypothesis of a mechanistic relationship between anisotropic displacement and hemodynamic forces related to the impingement of the blood on the lumen boundary. The presence of anisotropic displacement of the AAA lumen boundary and their link to hemodynamic forces have been assessed, highlighting a new possible role for hemodynamics in the study of AAA progression.


Detection of pneumococci in blood cultures by latex agglutination.
Latex agglutination by use of the Pneumoslide test on clinical blood cultures detected 22 Streptococcus pneumoniae strains as the etiological agents in 47 streptococcal septic episodes. The other 25 isolates were identified as viridans streptococci or streptococci of groups A, B, D, or G. The test demonstrated 100% sensitivity, 92% specificity, and predictive values for positive and negative reactions of 91 and 92%, respectively. Two false-positive reactions were caused by strains of viridans streptococci. The two strains continued to give positive reactions when colonies from blood agar plates were tested according to the instructions of the manufacturer. This latex agglutination test is an effective tool for the rapid diagnosis of pneumococci in blood cultures.


Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1.
CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1alpha, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption. Although the distribution of mature leukocytes was normal, steady state and induced trafficking and proliferation of myeloid progenitor cells were disordered in -/- mice. Moreover, mature neutrophils from -/- mice failed to chemotax in vitro and failed to mobilize into peripheral blood in vivo in response to MIP-1alpha. Consistent with this, -/- mice had accelerated mortality when challenged with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni eggs intravenously, and observed a 40% reduction in the size of lung granulomas in -/- mice compared to +/+ littermates. This was associated with increased interferon-gamma and decreased interleukin-4 production in -/- versus +/+ lung lymph node cells stimulated with egg-specific antigen, suggesting that CCR1 influences the inflammatory response not only through direct effects on leukocyte chemotaxis, but also through effects on the type 1-type 2 cytokine balance. Thus CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation.


Plane wave packet formulation of atom-plus-diatom quantum reactive scattering.
We recently interpreted several reactive scattering experiments using a plane wave packet (PWP) formulation of quantum scattering theory [see, e.g., S. C. Althorpe, F. Fernandez-Alonso, B. D. Bean, J. D. Ayers, A. E. Pomerantz, R. N. Zare, and E. Wrede, Nature (London) 416, 67 (2002)]. This paper presents the first derivation of this formulation for atom-plus-diatom reactive scattering, and explains its relation to conventional time-independent reactive scattering. We generalize recent results for spherical-particle scattering [S. C. Althorpe, Phys. Rev. A 69, 042702 (2004)] to atom-rigid-rotor scattering in the space-fixed frame, atom-rigid-rotor scattering in the body-fixed frame, and finally A+BC rearrangement scattering. The reactive scattering is initiated by a plane wave packet, describing the A+BC reagents in center-of-mass scattering coordinates, and is detected by projecting onto a series of AC+B (or AB+C) plane wave "probe" packets. The plane wave packets are localized at the closest distance from the scattering center at which the interaction potential can be neglected. The time evolution of the initial plane wave packet provides a clear visualization of the scattering into space of the reaction products. The projection onto the probe packets yields the time-independent, state-to-state scattering amplitude, and hence the differential cross section. We explain how best to implement the PWP approach in a numerical computation, and illustrate this with a detailed application to the H+D2 reaction.


Does radical nephrectomy with immunochemotherapy have any superiority over embolization alone in metastatic renal cell carcinoma? A preliminary report.
We evaluated the results and effects of radical nephrectomy followed by immunochemotherapy and embolization alone on the survival of patients with metastatic renal cell carcinoma. The study included 20 patients with histologically confirmed renal cell carcinoma. Ten patients were in the combined therapy group and the other 10 patients who were unable to undergo nephrectomy because of poor performance status or unresectable tumor were in the embolization group. Radical nephrectomy was performed on patients with good performance status (WHO criteria 0-1). Immunochemotherapy (interferon alpha 2a and 5-fluorouracil) was started within 1 month after surgery. A dose of 9 x 10(6) U/day interferon alpha 2a was subcutaneously administered 3 times a week. A dose of 750 mg/m2 5-fluorouracil was administered intravenously during 4 h in the first 5 days of treatment. 5-Fluorouracil therapy was converted to weekly intervals after the first 12 days. Combined therapy was continued for 3 months. Ethanol was used for transarterial embolization. The main renal arteries and parasitic arteries of the tumor were embolized. There were no significant differences in age distribution, sex, affected side, tumor size and T stage between the groups. After completion of the combined therapy, 6 patients showed progression at the first control. Only 1 patient (10 %) had stable disease throughout the 10 months after combined therapy. One patient died of myocardial infarction on the 4th day in the embolization group. While progressive disease within the first 3 months was detected in 6 patients, the other 3 patients (30%) had stable disease for 14, 17 and 55 months, respectively. There was no complete response in any group and no patient was alive (died of renal cell carcinoma) at the time of the analysis of the study data. Whereas the median survival time was 11 months (1-80) (mean +/- SE: 22.2 +/- 9.1) in the combined group, this time was a median of 1 month (1-74) (mean +/- SE: 17.5 +/- 8.6) in the embolization group. There was no statistically significant difference in survival time between the groups (p > 0.05). In this preliminary report, the clinical findings in embolization-group patients were definitively worse than the nephrectomy plus immunochemotherapy-group patients. In spite of these differences, combination therapy using radical nephrectomy and immunochemotherapy could not show superiority to embolization alone, especially in terms of survival time.


Incidence of central nervous system metastases in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with trastuzumab: A meta-analysis.
This study aimed to estimate the incidence of central nervous system (CNS) metastases in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with trastuzumab. Studies were identified through a literature search of electronic databases. Random-effects meta-analyses were performed to estimate the incidence rate of CNS metastases, trastuzumab therapy duration, and time from trastuzumab therapy to CNS metastasis diagnosis. A meta-analysis of odds ratios was performed to evaluate the significance of a difference in CNS metastasis incidence between patients with and without trastuzumab treatment. Thirty studies (8121 trastuzumab-treated and 3972 control patients) were included. The follow-up duration was 18.9 months (95% confidence interval [CI]: 13.8, 24.1). The trastuzumab treatment duration was 9.0 months (95% CI: 7.0, 11.0). The median interval between the start of trastuzumab therapy and CNS metastasis diagnosis was 12.2 months (95% CI: 9.5, 14.7). The incidence of CNS metastasis after the start of trastuzumab therapy was 22% (95% CI: 16, 27). The incidence of CNS metastases was significantly higher in trastuzumab-treated than in non-trastuzumab-treated patients (odds ratio: 1.39 [95% CI: 1.06, 1.82], p=0.02). The survival time from the start of the study was 23.4 months (95% CI: 19.7, 27.1) in trastuzumab-treated patients and 18.4 months (95% CI: 12.7, 24.1) in patients treated with control regimens. The survival time after the development of CNS metastases in trastuzumab-treated patients was 19.2 months (95% CI: 15.6, 25.9). Approximately 22% of patients with HER2-positive MBC who were treated with trastuzumab developed CNS metastases. However, trastuzumab-treated patients had a longer survival than patients who were not treated with trastuzumab.


[Treatment of end-stage diabetic nephropathy].
The progression of diabetic nephropathy can be halted by keeping blood glucose levels close to normal values. Three therapeutic approaches can be considered: intensive insulin treatment, islet of Langerhans transplantation, and pancreas transplantation. 1) The Diabetes Control and Complication Trials, a clinical study conducted from 1983 to 1993, showed that intensive insulin treatment prevented the development and slowed the progression of diabetic kidney disease by 50%. 2) In 2003, P. Fiorina studied the potential effects of islet transplantation on the renal function of 36 patients with type 1 diabetes and kidney transplant. An improvement in kidney graft survival rate and functioning [Na(+)/K(+)-ATP activity] was observed when compared with 12 patients with unsuccessful islet transplant. 3) P. Fioretto et al, in 2006, confirmed that normoglycemia for 10 years following pancreas transplantation alone reversed diabetic glomerulopathy lesions in native kidneys. This study also demonstrated that interstitial expansion was reversible and atrophic tubules were reassorbed. 4) P. Fiorina, in 2007, confirmed that simultaneous kidney-pancreas transplantation was associated with a better high-energy phosphate metabolism (as assessed by 31P-magnetic resonance spectroscopy) than in kidney- alone transplanted diabetic patients, suggesting that restoration of Beta cell function positively affects kidney graft metabolism.


Further morphological and electrophysiological studies on snake muscle spindles.
1. Electron microscope studies using ruthenium red, horseradish peroxidase, and colloidal lanthanum disclosed a feature characteristic of the snake spindle capsule: it consists of a single layer of flattened cells connected in series, each of which forms a cylinder enclosing the intrafusal fiber. 2. In intact spindles none of the markers penetrated the capsule. The diffusion barrier appeared to be located along the intercellular space near the inner surface of the capsule layer. Through the openings at the ends of the capsule the marker gained access to the periaxial space, but only for a limited distance. 3. Through a punctured hole in the capsule, ruthenium red had access to the periaxial space, disclosing a dense network consisting of fine filaments and granular structures. Since this space was also shown to contain alcian blue-positive substrate, the network may represent acid mucopolysaccharide (probably hyaluronic acid + protein molecules), which may account for the observed limited longitudinal diffusion of this dye in the periaxial space. The intercellular space between the intrafusal fiber, the sensory ending, and the satellite cell was filled with ruthenium red, and no special junction was found between these cells. 4. Using glass microelectrodes, potential profiles across the sensory region of muscle spindles of the snake were examined. 5. When the electrode was advanced through the capsular region, two steps of negative potential were usually observed. The first negative step of 5-10 mV was confirmed by fluorescent dye injection to be due to penetration of the capsule. The second larger step of 40-60 mV negative to the bathing solution was demonstrated by the dye injection to be due to penetration of the intrafusal fiber. Occasionally, a negative potential of 20-30 mV relative to the bathing solution was also recorded. This potential, characterized by small spikelike potentials occurring in synchrony with nerve impulses, was considered to be due to penetration of the sensory ending. 6. both the capsule and the intrafusal fiber showed rectification to injected currents. From input resistance, input capacitance and surface area specific resistance and capacitance were estimated with some assumptions to be 4.1-4.8 k omega . cm2 and 5.1-14.3 micro F/cm2 for the capsule, and 1.1-2.8 k omega . cm2 and 11-23 micro F/cm2 for the intrafusal fiber. The intrafusal fiber of short-capsule spindles lacked an action potential, whereas that of long-capsule spindles responded with an all-or-none action potential to depolarizing current. 7. In about half of the short-capsule spindles examined (8/15), current injected through an intracellular electrode in the intrafusal fiber neither initiated impulses in the afferent axon nor affected background nerve activity. The rest of the spindles responded to depolarizing current with initiation of nerve impulses and concomitant maintained contraction of the intrafusal fiber during applied current...


Activation of Hypoxia-Inducible Factor-1α Via Succinate Dehydrogenase Pathway During Acute Lung Injury Induced by Trauma/Hemorrhagic Shock.
Hypoxia-inducible factor (HIF)-1α is a transcription factor that is critical for tissue adaptation to hypoxia and inflammation. Previous studies had indicated that normoxic activation of HIF-1α in cancer involves inhibition or mutation of the metabolic enzyme succinate dehydrogenase (SDH). We have found that local inhibition of HIF-1α ameliorates acute lung injury (ALI) induced by trauma/hemorrhagic shock (T/HS) in rats. In this study, we found pulmonary activation of HIF-1α and inhibition of SDH during THS-induced ALI in rats and transcriptional activation of HIF-1α during ALI induced by T/HS lymph via SDH pathway in vitro. Furthermore, pharmacologic inhibition of HIF-1α attenuates lung inflammation and pulmonary edema during ALI by T/HS. Activation of HIF-1α is detrimental to ALI induced by T/HS. Thus, our data suggest that HIF-1α activation by T/HS is necessary for T/HS-induced lung injury and a critical role for SDH in the initiation of acute inflammatory response after ALI. Nevertheless, this is a preclinical work and several limitations impede translation of the findings to patients, such as uncontrolled bleeding and simultaneous treatment, and prolonged course of clinical shock on the outcome of the work, which needs to be addressed in future.


Stable, biocompatible lipid vesicle generation by solvent extraction-based droplet microfluidics.
In this paper, we present a microfluidic platform for the continuous generation of stable, monodisperse lipid vesicles 20-110 μm in diameter. Our approach utilizes a microfluidic flow-focusing droplet generation design to control the vesicle size by altering the system's fluid flow rates to generate vesicles with narrow size distribution. Double emulsions are first produced in consecutive flow-focusing channel geometries and lipid membranes are then formed through a controlled solvent extraction process. Since no strong solvents are used in the process, our method allows for the safe encapsulation and manipulation of an assortment of biological entities, including cells, proteins, and nucleic acids. The vesicles generated by this method are stable and have a shelf life of at least 3 months. Here, we demonstrate the cell-free in vitro synthesis of proteins within lipid vesicles as an initial step towards the development of an artificial cell.


Intrinsic noise in game dynamical learning.
Demographic noise has profound effects on evolutionary and population dynamics, as well as on chemical reaction systems and models of epidemiology. Such noise is intrinsic and due to the discreteness of the dynamics in finite populations. We here show that similar noise-sustained trajectories arise in game dynamical learning, where the stochasticity has a different origin: agents sample a finite number of moves of their opponents in between adaptation events. The limit of infinite batches results in deterministic modified replicator equations, whereas finite sampling leads to a stochastic dynamics. The characteristics of these fluctuations can be computed analytically using methods from statistical physics, and such noise can affect the attractors significantly, leading to noise-sustained cycling or removing periodic orbits of the standard replicator dynamics.


Successful silver impregnation of degenerating axons after long survivals in the human brain.
Degenerating axons in the human brain were successfully impregnated with reduced silver methods. The appearance of degenerating fibers did not differ markedly with survival times of three weeks and two, six, and twelve years following cerebral infarction or contusion of the brain. Impregnated fibers were found only along the appropriate corticofugal pathways. Electron microscopic examination of Vibratome-cut, silver-stained sections demonstrated silver deposition almost exclusively within axon fragments. Previous studies using anterograde degeneration methods in the human brain have limited their choice of cases to those with short periods of survival. Relaxing the restriction of short survival times extends the range of cases which can be used to study neural connections which may be unique to, or different in, the human brain.


GI distension in severe ulcerative colitis.
In previous retrospective studies in patients with severe ulcerative colitis (UC), small bowel distension was found to characterize a subgroup of patients at higher risk for both toxic megacolon (TMC) and multiple organ dysfunction syndrome (MODS). In this study we prospectively evaluated the prevalence of GI distension and its relationship to clinical outcome in patients with severe UC. Of 109 consecutive inpatients with acute UC (admitted to the GI Unit of the University of Rome during the period 1995-2000), 45 had severe colitis. Routine blood tests and acid-base balance and plain abdominal film evaluations were performed upon admission and repeated every 1-3 days. The gas content of the stomach and small and large intestines was evaluated on plain abdominal films. All patients were submitted to the standard Oxford intensive medical regimen; clinical improvement, occurrence of major complications, need for surgery, and mortality were evaluated. Statistical analysis was carried out using Student's t, chi2, Fisher's exact, Mann-Whitney, and Wilcoxon rank sum tests, when appropriate. Of 45 patients with severe UC, 24 (53%) had GI distension. Three of these 24 patients had TMC on admission (all underwent surgery and survived), 21 showed increased GI gas content (four developed TMC 1-4 days after the detection of GI distension and were operated on, two developed MODS and died, and eight did not improve but were submitted to surgery and survived). None of the 21 patients with normal GI gas content had complications; all survived (five did not improve and required surgery). In severe UC, persistent GI distension characterized a subgroup of patients with poor response to medical therapy and at higher risk for TMC and of need for surgery. The development of MODS was the most important predicting factor for fatal outcome.


New prosthetic restorative features of Ankylos implant system.
All oral implant systems rely on the abutment part of the implant to provide stability for the dental prosthetic. The Ankylos implant offers precisely machined, tapered-cone abutment (Morse taper) connection. This tapered abutment connection provides high resistance to bending and rotational torque during clinical function, which significantly reduces the possibilities of screw fracture or loosening. This report describes the design and mechanical construction characteristics of the Ankylos implant system that make it possible for the system to provide final restorations that are natural looking, esthetically acceptable, durable, and cost effective. Review of the clinical literature. The clinical results of singletooth crowns borne on Ankylos implants in the lateral tooth region are excellent after a minimum of 5 years in function (mean = 6.3 years) compared with the high prosthetic complication rate with other systems. Abutment loosening occurred in only 1.3% of the 233 innovative implants restored with crowns that were designed with a physiologically shaped occlusal surface. This implant system is exceptionally well suited for use in the restoration of missing natural teeth.


[Mental disorders and neuropsychological impairment related to chronic use of cannabis].
INTRODUCTION. Cannabis is an illegal drug in wide use nowadays, mainly for recreational purposes. It is considered one of the less harmful drugs, partly due to the large amount of information to which most people have access. However, the scientific literature could reveal important clues to the contrary. AIM. To gather and resume updated scientific data from different fields (clinical psychology, neurobiology, neuroimaging...) about the effects and consequences of the chronic use of cannabis. DEVELOPMENT. Evidence concerning the mental disorders and neuropsychological impairment associated the most to the chronic use is presented along with comments on the possible underlying neurobiological mechanisms, and the most important risk factors are also described. CONCLUSIONS. The evidence indicates that frequent and prolonged use of cannabis can be detrimental to mental health. A high risk of psychotic symptoms in predisposed individuals, higher for frequent users, is described, while the findings on symptoms of depression and anxiety are less consistent. On the cognitive-behavioral level, the functions most affected seem to be the attentional and executive ones. These data can be valuable both to guide further research and for updating the sensibilization and prevention programs on cannabis abuse.


The effect of an isoflavonid-rich liquorice extract on fermentation, methanogenesis and the microbiome in the rumen simulation technique.
Due to the antimicrobial activity of flavonoids, it has been suggested that they may provide a possible alternative to antibiotics to stimulate productivity and reduce the environmental load of ruminant agriculture. We hypothesised that an extract of liquorice, rich in prenylated isoflavonoids and particularly glabridin, might potentially improve the efficiency of nitrogen utilisation and reduce methane production in the rumen. When added to a long-term rumen simulating fermentor (RUSITEC), liquorice extract at 1 g L-1 decreased ammonia production (-51%; P < 0.001) without affecting the overall fermentation process. When added at 2 g L-1, decreases in not only ammonia production (-77%; P < 0.001), but also methane (-27%; P = 0.039) and total VFA production (-15%; P = 0.003) were observed. These effects in fermentation were probably related to a decrease in protozoa numbers, a less diverse bacteria population as well as changes in the structure of both the bacterial and archaeal communities. The inclusion of an isoflavonoid-rich extract from liquorice in the diet may potentially improve the efficiency of the feed utilisation by ruminants.


Monoethylglycinexylidide production as a measure in predicting hepatic histology.
To clarify whether monoethylglycinexylidide (MEGX) production can be useful in predicting the severity of chronic liver disease, 51 subjects were enrolled in this study: 13 mild-moderate CAH (group A), 9 severe CAH (group B), 29 cirrhosis, 18 compensated and 11 decompensated disease (group C). The patients were injected with a 1 mg/Kg lidocaine bolus i.v. and serum-sampled for MEGX values (time 15, 30 and 60 minutes), determined by TDX-immunoassay. MEGX formation was significantly different (Mann-Whitney U test) in the three groups at each time interval, especially at 30 min: group A = 70.5 +/- 9.9 ng/ml (mean +/- SD); group B = 49.7 +/- 7.2; group C = 37.2 +/- 19.5 (in A vs B, p = 0.0003; in A vs C, p < 0.0001; in B vs C, p = 0.0237). The difference between compensated and decompensated cirrhosis was always significant (p = 0.0099, 0.0005, 0.0113 respectively) but between severe CAH and compensated cirrhosis it was marginal only at 15min (p = 0.0763) and absent at 30 and 60min. At 30min MEGX values > 60 suggest mild-moderate CAH, < 40 cirrhosis, < 30 decompensated cirrhosis, between 40 and 60 severe CAH or compensated cirrhosis. We are of the opinion that the MEGX test could be utilized to predict hepatic histology.


Design of Synthetic Surrogates for the Macrolactone Linker Motif in Coibamide A.
A marine cyanobacterial cyclic depsipeptide, coibamide A (CbA), inhibits the mammalian protein secretory pathway by blocking the Sec61 translocon, which is an emerging drug target for cancer and other chronic diseases. In our previous structure-activity relationship study of CbA, the macrolactone ester linker was replaced with alkyl/alkenyl surrogates to provide synthetically accessible macrocyclic scaffolds. To optimize the cellular bioactivity profile of CbA analogues, novel lysine mimetics having β- and ε-methyl groups have now been designed and synthesized by a stereoselective route. A significant increase in cytotoxicity was observed upon introduction of these two methyl groups, corresponding to the d-MeAla α-methyl and MeThr β-methyl of CbA. All synthetic products retained the ability to inhibit secretion of a model Sec61 substrate. Tandem evaluation of secretory function inhibition in living cells and cytotoxicity was an effective strategy to assess the impact of structural modifications to the linker for ring closure.


Effect of short term fasting on plasma composition of lactating rats.
The effects of a 24-h fast upon plasma and blood components of the lactating rat on day 20 after parturition have been determined. Body weight decrease observed with fasting was more marked in nursing dams than in controls. The changes observed agree with a limited use of lipidic resources, exhaustion of liver glycogen and considerable utilization of amino acids as energetic - as well as gluconeogenetic - substrates. Blood and plasma glucose were maintained in fasted dams at a level comparable with that of controls. The actual variations observed in the plasma aminogram were limited, showing a remarkable maintenance of the dam's own amino-acid homeostasis.


Pediatric oncology services in Nepal.
Cancer in children is one of the emerging noncommunicable diseases in Nepal with significant morbidity and mortality. Significant efforts are being made at the government and nongovernment level to provide awareness, early diagnosis, and effective treatment to improve the cure rate of children with cancer. The major challenges include: lack of education, late diagnosis, advanced disease at presentation, financial problems, geographical and transportation difficulties, and inconsistent supply of chemotherapy medicines.


An unusual case of traumatic bilateral hip dislocation without fracture.
Bilateral traumatic hip dislocations are extremely rare. Most of these are related to acetabular or proximal femoral fractures, consisting of complex lesions, and are rarely pure ligamentous injuries. Posterior dislocation is the most frequent. Some dislocations are accompanied by sciatic nerve palsy. The present case is a posterior bilateral hip dislocation with no other associated lesions, there are very few reports published with this clinical setting. The patient had good functional outcome.


Generation of high-order harmonics with controllable elliptical polarization.
We propose and numerically demonstrate a method for obtaining high-harmonic radiation with desirable elliptical polarization. Atoms are shined by a combination of a strong linearly-polarized laser field and an additional weak field, which is elliptically polarized in a plane perpendicular to the polarization direction of the strong field. The strong driver ionizes and recollides electrons with their parent ion, while the weak field perturbatively drives the electrons away from "head-on" collision. Upon recombination, new elliptically polarized harmonics with same ellipticity as the weak driver are emitted at efficiency which linearly depends on the intensity of the weak beam, but is independent of its elilipticity.


Three-dimensional mechanisms of macro-to-micro-scale transport and absorption enhancement by gut villi motions.
We evaluate the potential for physiological control of intestinal absorption by the generation of "micromixing layers" (MMLs) induced by coordinated motions of mucosal villi coupled with lumen-scale "macro" eddying motions generated by gut motility. To this end, we apply a three-dimensional (3D) multigrid lattice-Boltzmann model of a lid-driven macroscale cavity flow with microscale fingerlike protuberances at the lower surface. Integrated with a previous 2D study of leaflike villi, we generalize to 3D the 2D mechanisms found there to enhance nutrient absorption by controlled villi motility. In three dimensions, increased lateral spacing within villi within groups that move axially with the macroeddy reduces MML strength and absorptive enhancement relative to two dimensions. However, lateral villi motions create helical 3D particle trajectories that enhance absorption rate to the level of axially moving 2D leaflike villi. The 3D enhancements are associated with interesting fundamental adjustments to 2D micro-macro-motility coordination mechanisms and imply a refined potential for physiological or pharmaceutical control of intestinal absorption.


[Interrelation between NO and H2O2 formation and their role in the regulation of ion homeostasis of cells].
The review deals with some problems of formation, utilization and functioning two of the most important and the lest cytotoxic active oxidative metabolites--NO and H2O2. The interrelation of NO and H2O2 cellular metabolism is reviewed. There are literature data regarding NO and H2O2 significance in the cellular signalling transduction and tissues paracrine regulation. The peculiar attention is dedicated to NO and H2O2 significance in the smooth muscle cells ion homeostasis regulation particularly in the uterus. As well there are the own author's data evidencing about the composite and ambiguous concentration-dependent physiological action of these metabolites. Varying in level in the cells NO and H2O2 may have a cyclic character similar to the oscillations of some other signaling molecules concentrations, evidently playing an important role in the mechanisms of cellular signal transduction and in the paracrine system.


Outcomes of limited stage primary bone diffuse large B-cell lymphoma in the rituximab era: a multicenter, retrospective study.
Primary bone diffuse large B cell lymphoma (DLBCL) is a rare variant of extranodal non-Hodgkin lymphoma (NHL) historically treated with induction chemotherapy followed by consolidative radiation therapy (RT). It remains unknown whether RT confers additional benefit following rituximab-based chemoimmunotherapy (CIT) induction in patients with limited-stage disease. We conducted a multicenter retrospective analysis of patients treated between 2005 and 2019 using rituximab-based CIT regimens with or without consolidative RT to discern whether consolidative RT adds benefit in patients with stage I-II disease that could be encompassed in one radiation field. A total of 112 patients were included: 78 received CIT and radiation (RT group), and 34 received CIT alone (no RT group). The OS at 10 years was 77.9% in the RT group and 89.0% in the no RT group (p = 0.42). The RFS at 10 years was 73.5% in the RT group and 80.3% in the no RT group (p = 0.88). Neither improved OS nor RFS was associated with the addition of consolidative RT. Subgroup analysis of patients only achieving a partial response after CIT suggests that these patients may benefit from consolidative RT.


Traditional uses, phytochemical, pharmacology, quality control and modern applications of two important Chinese medicines from Rosa laevigata Michx.: A review.
Rosa laevigata Michx. is an ethnic medicine that have strong biological activities used in the traditional medicine system for the treatment of diabetes, nephropathy, myocardial damage, oxidative damage, liver damage and so on. Currently, The Chinese herb R. laevigata Michx. can be divided into two important medicines: Fructus R. laevigata and Radix R. laevigata, from which approximately 148 chemical components have been isolated, including flavonoids, lignans, polyphenols, steroids, triterpenoids, tannins as well as other components. Pharmacological studies have already confirmed that both of these herbs have antioxidant, anti-inflammatory, antiviral and anti-tumor activities, as well as renal protective, immunomodulatory, lipid-lowering, cardiovascular protective, bacteriostatic, and other pharmacological effects. Toxicological tests and quality control studies revealed the safety and nontoxicity of R. laevigata Michx. Therefore, this paper systematically summarizes the traditional uses, botanical, phytochemical, and pharmacology as well as the quality control and toxicology of Fructus and Radix, which in order to provide a comprehensive reference for its continued research.


The piRNA response to BmNPV infection in the silkworm fat body and midgut.
Bombyx mori nucleopolyhedrovirus (BmNPV) is a DNA virus that causes huge losses to the silkworm industry but the piRNA responses during BmNPV infection in the silkworm remain uninvestigated. Here, silkworm piRNA profiles of uninfected and BmNPV-infected fat body and midgut were determined by high-through sequencing in the early stages of BmNPV infection. A total of 2675 and 3396 genome-derived piRNAs were identified from fat body and midgut, respectively. These genome-derived piRNAs mainly originated from unannotated instead of transposon regions in the silkworm genome. In total, 572 piRNAs were associated with 280 putative target genes in fat body and 805 piRNAs with 380 target genes in midgut. Compared to uninfected tissues, 322 and 129 piRNAs were significantly upregulated in BmNPV-infected fat body and midgut, respectively. In addition, 276 and 117 piRNAs were significantly downregulated. Moreover, differentially expressed (DE) piRNAs during BmNPV infection differed significantly between fat body and midgut. Putative DE piRNA-targeted genes were associated with "response to stimulus" and "environmental information processing" in fat body after infection with BmNPV, which may indicate an active piRNA response to BmNPV infection in fat body. This study may lay the foundation for future research of the potential roles of the piRNA pathway and specific piRNAs in BmNPV pathogenesis.


Term angular pregnancy with placenta accreta. A case report.
A 27-year-old primigravida, with two prior adnexal operations, had retained placenta with postpartum haemorrhage following an uncomplicated vaginal delivery. Laparotomic removal revealed placental accretism. Pharmacological treatment (oxytocin and sulprostone) and right cornual resection failed to control profuse bleeding. In the end, subtotal hysterectomy was unavoidable.


Developing a model of adolescent friendship formation on the internet.
Previous research has been largely silent about what precisely influences online friendship formation and has ignored motives for online communication as potential explanations. Drawing on a sample of 493 adolescents, this study tested a path model of adolescent friendship formation including as predictors introversion/extraversion, online self-disclosure, motive for social compensation, and frequency of online communication. Our path analysis showed that extraverted adolescents self-disclosed and communicated online more frequently, which, in turn, facilitated the formation of online friendships. Introverted adolescents, by contrast, were more strongly motivated to communicate online to compensate for lacking social skills. This increased their chances of making friends online. Among introverted adolescents, a stronger motive for social compensation also led to more frequent online communication and online self-disclosure, resulting in more online friendships. The model suggests that the antecedents of online friendship formation are more complex than previously assumed and that motives for online communication should be studied more closely.


Selective Separation of Pd(II) on Pyridine-Functionalized Graphene Oxide Prepared by Radiation-Induced Simultaneous Grafting Polymerization and Reduction.
The recovery of precious metals like palladium (Pd) from secondary resources has enormous economic benefits and is in favor of resource reuse. In this work, we prepared a high efficiency pyridine-functionalized reduced graphene oxide (rGO) adsorbent for selective separation of Pd(II) from simulated electronic waste leachate, by one-pot γ-ray radiation-induced simultaneous grafting polymerization (RIGP) of 4-vinylpyridine (4VP) from graphene oxide (GO) and reduction of GO. The poly(4-vinylpyridine)-grafted reduced graphene oxide (rGO-g-P4VP) exhibits fast adsorption kinetics and high maximum adsorption capacity. The adsorption capacity is 105 mg g-1 in the first minute and reaches equilibrium within 120 min. The adsorption process follows the Langmuir model, from which the maximum adsorption capacity of Pd(II) is estimated to be 177 mg g-1. We also proved that the adsorption mechanism of Pd(II) on rGO-g-P4VP involves both ion exchange and coordination adsorption by XPS analysis. Most importantly, the loss of oxygen-containing groups due to reduction of GO not only facilitates the separation of adsorbent from aqueous solution but also reduces the electrostatic repulsion toward Pd(II)Cl42- in hydrochloric acid solution, leading to a higher adsorption selectivity of Pd(II) over some common metal cations in electronic waste including Fe(III), Cu(II), and Al(III) compared with poly(4-vinylpyridine)-grafted graphene oxide (GO-g-P4VP) prepared by atom transfer radical polymerization. Other precious metals like Pt(IV) and Au(III) can also be recovered easily and selectively by rGO-g-P4VP. This work demonstrates that rGO-g-P4VP prepared by the facile RIGP is a promising adsorbent for recovery of precious metals from secondary resources like electronic waste leachate.


Nosocomial keratitis caused by methicillin-resistant Staphylococcus aureus: case report and preventative measures.
A 47-year-old African-American woman was admitted to the intensive care unit of our community hospital for respiratory failure secondary to severe decompensated heart failure, requiring intubation. In the ensuing days, she developed a methicillin-resistant Staphylococcus aureus (MRSA) infection of the cornea, despite no growth of MRSA in multiple blood, sputum, and urine cultures. This unexpected corneal infection complicated her hospital stay, and increased morbidity and disease-related cost. Risk factors, warning signs, and preventative measures for MRSA keratitis secondary to lagophthalmos (inability to completely close one's eyelids) are outlined in this case report. Implementing simple precautions such as taping eyelids shut or using artificial lubrication may reduce patient morbidity and disease-related costs. These recommendations are directed to non-ophthalmic clinicians who provide care to patients in settings where MRSA colonization is widespread.


[An experience applying a spiritual care model to a first-time stroke patient].
Patients with stroke-related disabilities are at risk of depression and social isolation. This can make it difficult for the patient to cope with his or her disease and increase caregiver burden. While good at dealing with physical illness, nurses are often poor at attending to patients' mental and spiritual needs. In this paper, the authors introduce their experience using a spiritual care model to care for a stroke patient. The patient, a 69 year-old retiree, was admitted to our hospital due to an acute stroke. During hospitalization, he suffered from acute confusion and persistent focal weakness. His disability resulted in physical dependence, which did not improve during rehabilitation. We used a model of spiritual care and in-depth evaluation to identify several underlying psychological issues. These included feelings of hopelessness and loss of control and motivation. The authors established trust through active listening. In addition to standard nursing education and physical care, we, in cooperation with the patient's children, provided encouragement and support to help the patient cope with his disease burden and actively participate in rehabilitation. We applied a multi-dimensional spiritual care approach to help the patient shift from hopelessness to hopefulness. This enhanced his motivation to participate in rehabilitation and improved his self-care abilities. We hope this case report on the application of a spiritual-care model is useful reference for nurses responsible to care for stroke patients.


Hominoid-specific SPANXA/D genes demonstrate differential expression in individuals and protein localization to a distinct nuclear envelope domain during spermatid morphogenesis.
Human sperm protein associated with the nucleus on the X chromosome consists of a five-member gene family (SPANXA1, SPANXA2, SPANXB, SPANXC and SPANXD) clustered at Xq27.1. Evolved from an ancestral SPANX-N gene family (at Xq27 and Xp11) present in all primates as well as in rats and mice, the SPANXA/D family is present only in humans, bonobos, chimpanzees and gorillas. Among hominoid-specific genes, the SPANXA/D gene family is considered to be undergoing rapid positive selection in its coding region. In this study, RT-PCR of human testis mRNA from individuals showed that, although all SPANXA/D genes are expressed in humans, differences are evident. In particular, SPANXC is expressed only in a subset of men. The SPANXa/d protein localized to the nuclear envelope of round, condensing and elongating spermatids, specifically to regions that do not underlie the developing acrosome. During spermiogenesis, the SPANXa/d-positive domain migrated into the base of the head as the redundant nuclear envelope that protrudes into the residual cytoplasm. Post-testicular modification of the SPANXa/d proteins was noted, as were PEST (proline, glutamic acid, serine, and threonine rich regions) domains. It is concluded that the duplication of the SPANX-N gene family that occurred 6-11 MYA resulted in a new gene family, SPANXA/D, that plays a role during spermiogenesis. The SPANXa/d gene products are among the few examples of X-linked nuclear proteins expressed following meiosis. Their localization to non-acrosomal domains of the nuclear envelope adjacent to regions of euchromatin and their redistribution to the redundant nuclear envelope during spermiogenesis provide a biomarker for the redundant nuclear envelope of spermatids and spermatozoa.


Epidural abscess secondary to acute appendicitis.
A 62-year-old man presented via the emergency department with a 1-week history of back pain, on a background of non-insulin-dependent diabetes mellitus and rectal carcinoma for which he had undergone abdominoperineal resection, chemotherapy and radiotherapy. He exhibited signs of sepsis, midline lumbar spine tenderness and reduced hip flexion. CT of the abdomen and pelvis showed a presacral collection contiguous with the tip of the appendix, and MRI lumbar spine revealed abscess invation into the epidural space extending to T9. He underwent a laparotomy with washout of the presacral abscess and appendicectomy and prolonged course intravenous antibiotic therapy. At 3 months after initial presentation he had made a full clinical recovery with progressive radiological resolution of the epidural abscess. The objective of the case report is to highlight a unique and clinically significant complication of a very common pathology (appendicitis) and to briefly discuss other intra-abdominal sources of epidural abscess.


Population Coding of Capsaicin Concentration by Sensory Neurons Revealed Using Ca2+ Imaging of Dorsal Root Ganglia Explants from Adult pirt-GCaMP3 Mouse.
Nociceptors detect noxious capsaicin (CAPS) via the transient receptor potential vanilloid 1 (TRPV1) ion channel, but coding mechanisms for relaying CAPS concentration [CAPS] remain obscure. Prolonged (up to 1h.) exposure to CAPS is used clinically to desensitise sensory fibres for treatment of neuropathic pain, but its signalling has typically been studied in cultures of dissociated sensory neurons employing low cell numbers and very short exposure times. Thus, it was pertinent to examine responses to longer CAPS exposures in large populations of adult neurons. Confocal fluorescence microscopy was used to monitor the simultaneous excitation by CAPS of neuronal populations in intact L3/4 dorsal root ganglia (DRG) explants from adult pirt-GCaMP3 mice that express a cytoplasmic, genetically-encoded Ca2+ sensor in almost all primary sensory neurons. Peak analysis was performed using GraphPad Prism 9 to deconstruct the heterogenous and complex fluorescence signals observed into informative, readily-comparable measurements: number of signals, their lag time, maximum intensity relative to baseline (Max.) and duration. Exposure for 5 min. to CAPS activated plasmalemmal TRPV1 and led to increased fluorescence due to Ca2+ entry into DRG neurons (DRGNs), as it was prevented by capsazepine or removal of extracellular Ca2+. Increasing [CAPS] (0.3, 1 and 10 μM, respectively) evoked signals from more neurons (123, 275 and 390 from 5 DRG) with shorter average lag (6.4 ± 0.4, 3.3 ± 0.2 and 1.9 ± 0.1 min.) and longer duration (1.4 ± 0.2, 2.9 ± 0.2 and 4.8 ± 0.3 min.). Whilst raising [CAPS] produced a modest augmentation of Max. for individual neurons, those with large increases were selectively expedited; this contributed to a faster onset and higher peak of cumulative fluorescence for an enlarged responding neuronal population. CAPS caused many cells to fluctuate between high and low levels of fluorescence, with consecutive pulses increasing Max. and duration especially when exposure was extended from 5 to 20 min. Such signal facilitation counteracted tachyphylaxis, observed upon repeated exposure to 1 μM CAPS, preserving the cumulative fluorescence over time (signal density) in the population. Individual neurons within DRG differed extensively in the dynamics of response to CAPS, but systematic changes elicited by elevating [CAPS] increased signal density in a graded manner, unveiling a possible mechanism for population coding of responses to noxious chemicals. Signal density is sustained during prolonged and repeated exposure to CAPS, despite profound tachyphylaxis in some neurons, by signal facilitation in others. This may explain the burning sensation that persists for several hours when CAPS is used clinically.


[An old female case of vero-cytotoxin-producing Escherichia coli O-157: H7 infection].
It is well known that verocytotoxin-producing Escherichia coli O-157 : H7 infection can be severe in elderly persons. We report an 82-year-old female case of verocytotoxin-producing Escherichia coli O-157 : H7 infection. She was admitted to our hospital because of bloody diarrhea. The hemolytic-uremic syndrome (HUS) was not occurred, but systemic edema, ascites, pleural effusion and pulmonary edema with hypoxyemia gradually appeared. Treatment with human immunoglobulin in addition to fluid therapy, antibiotics, diuretics and human serum albumin resulted in dramatic improvement. Management of complications such as sepsis and electrolyte disturbance caused by this infection was considered to be important in elderly patients.


Employment and Adults Who Are Deaf or Hard of Hearing: Current Status and Experiences of Barriers, Accommodations, and Stress in the Workplace.
In an integrative review of the literature covering the period 2004-2016, the author presents a current picture of the situation of people who are deaf or hard of hearing (DHH) relative to employment and careers-particularly the barriers, facilitators, and stress levels experienced by working DHH adults. First, an overview is provided of findings from recent reports on employment outcomes for people who are DHH. Second, the author reviews the literature on employment and workplace barriers, facilitators, and accommodations for people who are DHH, and relates findings about DHH people's workplace-related stress and fatigue levels and the associated issues of job demand, job control, and social support in the workplace. The article concludes with a discussion of the implications of these findings, in particular the ways in which barriers to full participation of DHH people in the labor market can be addressed.


Keratitis by Paecilomyces lilacinus: A case report from Sub-Himalayan region.
Paecilomyces lilacinus is a filamentous fungus found in soil and air, which is a rare cause of ocular infection. The majority of case reports involving P. lilacinus among healthy hosts are of endophthalmitis and keratitis. We report a rare case of keratomycosis by P. lilacinus, in an immunocompetent, which responded well to treatment with ketoconazole. Some species belonging to the genus Paecilomyces such as P. lilacinus generally shows a poor response to conventional antifungal drugs. Therefore, correct identification of clinical isolates to the species level is mandatory for the appropriate treatment of the disease.


Circulating tumor cell-derived organoids: Current challenges and promises in medical research and precision medicine.
Traditional 2D cell cultures do not accurately recapitulate tumor heterogeneity, and insufficient human cell lines are available. Patient-derived xenograft (PDX) models more closely mimic clinical tumor heterogeneity, but are not useful for high-throughput drug screening. Recently, patient-derived organoid cultures have emerged as a novel technique to fill this critical need. Organoids maintain tumor tissue heterogeneity and drug-resistance responses, and thus are useful for high-throughput drug screening. Among various biological tissues used to produce organoid cultures, circulating tumor cells (CTCs) are promising, due to relative ease of ascertainment. CTC-derived organoids could help to acquire relevant genetic and epigenetic information about tumors in real time, and screen and test promising drugs. This could reduce the need for tissue biopsies, which are painful and may be difficult depending on the tumor location. In this review, we have focused on advances in CTC isolation and organoid culture methods, and their potential applications in disease modeling and precision medicine.


Influenza preparedness and the bureaucratic reflex: anticipating and generating the 2009 H1N1 event.
This paper draws together work on the event to problematise the generative implications of anticipatory governance in the management of emerging infectious disease. Through concerns for preparedness, the need to anticipate outbreaks of disease has taken on a new urgency. With the identification of the H1N1 virus circulating amongst human populations in 2009, public health measures and security practices at regional, national and international levels were rapidly put into play. However, as the ensuing event demonstrated, the social, political and economic disruptions of emerging infectious diseases can be matched by those of anticipatory actions. I argue that the event-making potential of surveillance practices and the pre-determined arrangements of influenza preparedness planning, when triggered by the H1N1 virus, caused an event acceleration through the hyper-sensitised global health security architecture. In the UK, this led to a bureaucratic reflex, a security response event that overtook the present actualities of the disease. This raises questions about the production of forms of insecurity by the security apparatus itself.


[Kyrle's disease].
Hyperkeratosis follicularis et parafollicularis in cuten penetrans known as Kyrle's disease is a recessive hereditary genodermatosis. Generally, Kyrle's disease appears between 30 to 50 years of age and women are affected more than men. We report a case of a 40-year-old man, a worker in a cement factory, who noticed the first skin lesions six years ago. Those were follicular papules on the left leg. He had been in good health beforehand, although an alcoholic for many years. Based on laboratory and other findings, chronic hepatitis was diagnosed. Histopathological analysis of skin lesions showed presence of hyperkeratosis and partial parakeratosis with acanthosis of the epidermis. Kyrle's disease is classified among the perforating dermatoses with perforating folliculitis, perforating serpiginous elastosis and perforating reactive collagenosis. Kyrle's disease is often associated with hepatic, renal or diabetic disorders, and may be a paraneoplastic disease. The course of this disease is chronic. If the associated diseases are treated, patients may have a better prognosis.


BitTorious: global controlled genomics data publication, research and archiving via BitTorrent extensions.
Centralized silos of genomic data are architecturally easier to initially design, develop and deploy than distributed models. However, as interoperability pains in EHR/EMR, HIE and other collaboration-centric life sciences domains have taught us, the core challenge of networking genomics systems is not in the construction of individual silos, but the interoperability of those deployments in a manner embracing the heterogeneous needs, terms and infrastructure of collaborating parties. This article demonstrates the adaptation of BitTorrent to private collaboration networks in an authenticated, authorized and encrypted manner while retaining the same characteristics of standard BitTorrent. The BitTorious portal was sucessfully used to manage many concurrent domestic Bittorrent clients across the United States: exchanging genomics data payloads in excess of 500GiB using the uTorrent client software on Linux, OSX and Windows platforms. Individual nodes were sporadically interrupted to verify the resilience of the system to outages of a single client node as well as recovery of nodes resuming operation on intermittent Internet connections. The authorization-based extension of Bittorrent and accompanying BitTorious reference tracker and user management web portal provide a free, standards-based, general purpose and extensible data distribution system for large 'omics collaborations.


Elucidation of chemosensitization effect of acridones in cancer cell lines: Combined pharmacophore modeling, 3D QSAR, and molecular dynamics studies.
Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules. Molecular dynamics simulations were performed for compound 10 and human P-glycoprotein (obtained from Homology modeling). An efficient pharmacophore containing 2 hydrogen bond acceptors and 3 aromatic rings (AARRR.14) was identified. NCI 2012 chemical database was screened against AARRR.14 CPH and identified 25 best-fit molecules. Potential regions of the compound were identified through Field (Gaussian) based QSAR. Regression analysis of atom-based QSAR resulted in r2 of 0.95 and q2 of 0.72, whereas, regression analysis of field-based QSAR resulted in r2 of 0.92 and q2 of 0.87 along with r2cv as 0.71. The fate of the acridone molecule (compound 10) in the P-glycoprotein environment is analyzed through analyzing the conformational changes occurring during the molecular dynamics simulations. Combined data of different in silico techniques provided basis for deeper understanding of structural and mechanistic insights of interaction phenomenon of acridones with P-glycoprotein and also as strategic basis for designing more potent molecules for anti-cancer and multidrug resistance reversal activities.


The association of homocysteine with metabolic syndrome in a community-dwelling population: homocysteine might be concomitant with metabolic syndrome.
Elevated plasma total homocysteine (tHcy) and metabolic syndrome (MetS) are both associated with cardiovascular disease, but the association between tHcy and MetS is not well characterized. The aim of this study was to determine the relationship between tHcy and MetS. To further estimate the time-dependent association of tHcy and MetS, we analyzed the tHcy level and MetS in 1499 subjects from a 4.8-year longitudinal study in Beijing, People's Republic of China. In multiple linear regression analysis, baseline tHcy levels associated with age, BMI, SBP, DBP, LDL-C and Cr independently over 4.8-years follow-up; age, BMI, SBP, DBP and Cr were found to be associated with tHcy levels independently at the end of follow-up. Logistic regression analysis showed that there was no association between the baseline tHcy level and MetS over the 4.8-year follow-up (odds ratio (OR), 1.32; 95% confidence interval (CI), 0.79-2.19; P = 0.282); rather, there was an association only with hypertension as a MetS component (OR, 1.53; 95% CI, 1.06-2.21; P = 0.024). tHcy levels were associated with MetS at both cross-sectional baseline (OR, 1.38; 95% CI, 1.02-1.88; P = 0.038) and cross-sectional follow-up (OR, 1.60; 95% CI, 1.02-2.50; P = 0.041). The tHcy levels of MetS subjects were higher than those of non-MetS subjects at both cross-sectional baseline (19.35 ± 7.92 µmol/L vs. 17.45 ± 6.70 µmol/L, respectively; P = 0.001) and cross-sectional follow-up (18.95 ± 7.15 µmol/L vs. 17.11 ± 5.98 µmol/L, respectively; P = 0.02). The tHcy level was not predictive of the incidence of MetS; however, it may be a risk factor for hypertension as a MetS component. Furthermore, tHcy levels were associated with MetS at cross-sectional baseline and follow-up, which suggests that a higher level of tHcy might be concomitant with MetS.


Nondispersive Infrared Gas Analyzer for Vapor Density Measurements of a Carbonyl-Containing Organometallic Cobalt Precursor.
A nondispersive infrared (NDIR) gas analyzer was demonstrated for measuring the vapor-phase density of the carbonyl-containing organometallic cobalt precurso μ2-η2-(tBu-acetylene) dicobalthexacarbonyl (CCTBA). This sensor was based on direct absorption by CCTBA vapor in the C≡O stretching spectral region and utilized a stable, broadband IR filament source, an optical chopper to modulate the source, a bandpass filter for wavelength isolation, and an InSb detector. The optical system was calibrated by selecting a calibration factor to convert CCTBA absorbance to a partial pressure that, when used to calculate CCTBA flow rate and CCTBA mass removed from the ampoule, resulted in an optically determined mass that was nominally equal to a gravimetrically-determined mass. In situ Fourier transform infrared (FT-IR) spectroscopy was performed simultaneously with the NDIR gas analyzer measurements under selected conditions in order to characterize potential spectroscopic interferences. Interference due to CO evolution from CCTBA was found to be small under the flow conditions employed here. A CCTBA minimum detectable molecular density as low as ≈3 × 1013 cm-3 was calculated (with no signal averaging and for a sampling rate of 200 Hz). While this NDIR gas analyzer was specifically tested for CCTBA, it is suitable for characterizing the vapor delivery of a range of carbonyl-containing precursors.


Cocoa powder increases postprandial insulinemia in lean young adults.
We hypothesized that chocolate products elicit higher insulin responses than matched products with alternate flavoring. To test this, we used a within-subject, repeated-measures comparison of six pairs of foods, one flavored with chocolate (cocoa powder) and the other not. Healthy subjects (n = 10, 4 men, 6 women) tested each pair of foods. Postprandial glucose and insulin levels were determined at intervals over 2 h using standardized glycemic index (GI) methodology. The product categories were chocolate bars, cakes, breakfast cereals, ice creams, flavored milks and puddings. Although the GI did not differ within each pair, the insulin index (II) of the chocolate product was always higher, by a mean of 28%, than the alternate flavored product (P < 0.001). The greatest difference occurred within the flavored milk category in which the chocolate version elicited 45% greater insulinemia than the strawberry flavored milk (P = 0.021). Macronutrient composition (fat, protein, sugar, fiber or energy density) accounted for nearly all of the variation in GI among the foods, but did not explain differences in insulinemia. The presence of cocoa powder in foods leads to greater postprandial insulin secretion than alternate flavorings. Specific insulinogenic amino acids or greater cephalic phase insulin release may explain the findings.