Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. However, as they inhibit platelet aggregation and prolong bleeding time they could cause increased perioperative bleeding. The overall risk remains unclear. This review was originally published in 2005 and was updated in 2010 and in 2012. The primary objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy. Our secondary outcome was to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); MEDLINE (inception until October 2012); EMBASE (inception until October 2012); Current Problems (produced by the UK Medicines Control Agency), MedWatch (produced by the US Food and Drug Administration) and the Australian Adverse Drug Reactions Bulletins (to May 2010). The original search was performed in August 2004. We also contacted manufacturers and researchers in the field. We included randomized controlled trials assessing NSAIDs in children, up to and including 16 years of age, undergoing elective tonsillectomy or adenotonsillectomy. Two authors independently assessed trial quality and extracted the data. We contacted study authors for additional information, where necessary. We included 15 studies that involved 1101 children in this updated review. One study was added as a result of our 2012 search, another previously included study was removed due to lack of randomization. Fourteen included studies compared NSAIDs with other analgesics or placebo and reported on bleeding requiring surgical intervention. The use of NSAIDs was associated with a non-significant increase in the risk of bleeding requiring surgical intervention: Peto odds ratio (OR) 1.69 (95% confidence interval (CI) 0.71 to 4.01). Ten studies involving 365 children reported perioperative bleeding requiring non-surgical intervention. NSAIDs did not significantly alter the number of perioperative bleeding events requiring non-surgical intervention: Peto OR 0.99 (95% CI 0.41 to 2.40) but the confidence intervals did not exclude an increased risk. Thirteen studies involving 1021 children reported postoperative vomiting. There was less vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used: Mantel Haenszel (M-H) risk ratio (RR) 0.72 (95% CI 0.61 to 0.85). There is insufficient evidence to exclude an increased risk of bleeding when NSAIDs are used in paediatric tonsillectomy. They do however confer the benefit of a reduction in vomiting.


[Herpes zoster in general medicine: experience of the Italian group Netaudit].
Herpes zoster is caused by the reactivation of the varicella-zoster virus (VZV) and usually appears many years after primary infection (varicella), induced by immunosuppression due to underlying diseases. Few epidemiological data in Italy are available concerning Herpes zoster, mainly because disease notification is not mandatory. An observational perspective trial was conducted for 12 months by 41 Italian general practitioners belonging to the Netaudit network to determine herpes zoster incidence and its correlation to patients' characteristics (age, gender, educational qualification, co-morbidities), the delay from correct diagnosis to the start of treatment and different drug prescription. In all, the study involved 193 patients with herpes zoster: this population included mostly female (60.6%) and elderly subjects (59.6%) with a mean age of 60.4 years. 46.1% of patients presented underlying diseases (diabetes 13%, solid tumours 5.7%). Correct diagnosis was achieved after a mean delay of 49 hours while therapy was started within 48 hours in most cases (75.1%). Aciclovir (51%) and valaciclovir (24%) were the most commonly used drugs. A significant correlation between educational level and prompt treatment suggests the major role of education in primary health prevention campaigns.


[The advances on the formation and toxic effects of haloacetaldehydes disinfection by-products in drinking water].
Haloacetaldehydes (HALs), as emerging disinfection by-products in drinking water, are the third largest group by weight of identified disinfection by-products (DBPs) in drinking water. The formation of HALs is associated with the level of natural organic matter and halide in the source water, the treatment process of drinking water and the type of disinfectant. Recent studies have shown that HALs are more cytotoxic and genotoxic than regulated trihalomethanes and halo-acetic acids in drinking water. Currently, only a few countries and regions have set limit values for trichloroacetaldehyde with high detection rate in drinking water. However, there is growing evidence that unregulated HALs have a higher potential risk to human health compared to regulated HALs. This paper reviews the current research progress on the formation and transformation, cytotoxicity and genotoxicity of HALs in drinking water, and looks forward to the problems that should be paid attention in the future toxicological research of HALs in order to support the development of scientific drinking water standards.


Surface-dominated transport and enhanced thermoelectric figure of merit in topological insulator Bi(1.5)Sb(0.5)Te(1.7)Se(1.3).
We report the observation of an order of magnitude enhancement of the thermoelectric figure of merit (ZT = 0.36) in topological insulator Bi1.5Sb0.5Te1.7Se1.3 nanowires at 300 K as compared with the bulk specimen (ZT = 0.028). The enhancement was primarily due to an order of magnitude increase in the electrical conductivity of the surface-dominated transport and thermally activated charge carriers in the nanowires. Magnetoresistance analysis revealed the presence of Dirac electrons and determined that the Fermi level was near the conduction band edge. This may be the first thermoelectric measurement of samples with a chemical potential in the gap of a topological insulator without gate tuning, and provides an opportunity to study the contribution of surface states to the Seebeck coefficient and resistivity without concern for the complex effect of band bending.


Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice.
Down Syndrome (DS) is a highly complex developmental genetic disorder caused by trisomy for human chromosome 21 (Hsa21). All individuals with DS exhibit some degree of brain structural changes and cognitive impairment; mouse models such as Ts65Dn have been instrumental in understanding the underlying mechanisms. Several phenotypes of DS might arise from a reduced response of trisomic cells to the Sonic Hedgehog (SHH) growth factor. If all trisomic cells show a similar reduced response to SHH, then up-regulation of the pathway in trisomic cells might ameliorate multiple DS phenotypes. We crossed Ptch1tm1Mps/+ mice, in which the canonical SHH pathway is expected to be up-regulated in every SHH-responsive cell due to the loss of function of one allele of the pathway suppressor, Ptch1, to the Ts65Dn DS model and assessed the progeny for possible rescue of multiple DS-related phenotypes. Down-regulation of Ptch produced several previously unreported effects on development by itself, complicating interpretation of some phenotypes, and a number of structural or behavioral effects of trisomy were not compensated by SHH signaling. However, a deficit in a nest-building task was partially restored in Ts;Ptch+/- mice, as were the structural anomalies of the cerebellum seen in Ts65Dn mice. These results extend the body of evidence indicating that reduced response to SHH in trisomic cells and tissues contributes to various aspects of the trisomic phenotype.


Narrowed petrous carotid canal detection for the early diagnosis of moyamoya disease.
Patients with moyamoya disease (MMD) exhibit narrowed internal carotid arteries (ICAs) because the distal ends of the bilateral ICAs have become progressively stenosed, starting mainly in childhood. Accordingly, the petrous carotid canals in MMD patients are suspected to be more hypoplastic than those in control subjects. In this study, the diagnostic value of conventional computed tomography for MMD patients was retrospectively evaluated by comparing the caliber of the bilateral carotid canals in MMD patients with that in control subjects. Thirty-five patients with MMD (15 males, 20 females; age range/average age: 6-71 / 26.1 years old) and age- and sex-matched control subjects underwent conventional head computed tomography. The maximal petrous carotid canal diameters of the two groups were measured and compared. The maximal petrous carotid canal diameter was significantly smaller in the moyamoya patients (mean +/- standard deviation [mm] = 4.70 +/- 0.61) than in the control subjects (5.62 +/- 0.61, p < 0.01). Conventional head computed tomography revealed narrowed petrous carotid canals in the MMD patients. This basic information could be utilized to screen patients who will require further examination, especially among those with underlying MMD.


Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking.
Many developmental processes break left-right (LR) symmetry with a consistent handedness. LR asymmetry emerges early in development, and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton. However, the nature of the underlying chirally asymmetric cytoskeletal processes has remained elusive. In this study, we combine thin-film active chiral fluid theory with experimental analysis of the C. elegans embryo to show that the actomyosin cortex generates active chiral torques to facilitate chiral symmetry breaking. Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling. Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis. Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.


The epidemiology of influenza.
Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic.


Elevated serum interferon-gamma in atopic asthma correlates with increased airways responsiveness and circadian peak expiratory flow variation.
Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an important role in chronic airway inflammation in asthmatic subjects. Increased airways responsiveness and nocturnal airway obstruction are important clinical manifestations of asthma. The aim of this study was to investigate whether IL-4, IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic asthmatics and eight nonatopic healthy subjects were determined at 16:00 and 04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method. The clinical manifestation of asthma was determined by assessment of the degree of airway obstruction, airways responsiveness to methacholine and severity of nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were significantly higher in asthmatic subjects as compared to healthy controls, both at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points correlated significantly with the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= - 0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no relationship was found between the levels of IL-4 and IL-5 and the parameters of clinical manifestation of asthma. The results suggest that the serum interferon-gamma level is a reflection of the severity of airway inflammation in atopic asthma. More studies are needed to detect the cellular sources and to clarify the exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.


The impact of scopolamine pretreatment on 3-iodothyronamine (T1AM) effects on memory and pain in mice.
We previously demonstrated that 3-iodothyronamine (T1AM), a by-product of thyroid hormone metabolism, pharmacologically administered to mice acutely stimulated learning and memory acquisition and provided hyperalgesia with a mechanism which remains to be defined. We now aimed to investigate whether the T1AM effect on memory and pain was maintained in mice pre-treated with scopolamine, a non-selective muscarinic antagonist expected to induce amnesia and, possibly, hyperalgesia. Mice were pre-treated with scopolamine and, after 20min, injected intracerebroventricularly (i.c.v.) with T1AM (0.13, 0.4, 1.32μg/kg). 15min after T1AM injection, the mice learning capacity or their pain threshold were evaluated by the light/dark box and by the hot plate test (51.5°C) respectively. Experiments in the light/dark box were repeated in mice receiving clorgyline (2.5mg/kg, i.p.), a monoamine oxidase (MAO) inhibitor administered 10min before scopolamine (0.3mg/kg). Our results demonstrated that 0.3mg/kg scopolamine induced amnesia without modifying the murine pain threshold. T1AM fully reversed scopolamine-induced amnesia and produced hyperalgesia at a dose as low as 0.13μg/kg. The T1AM anti-amnestic effect was lost in mice pre-treated with clorgyline. We report that the removal of muscarinic signalling increases T1AM pro learning and hyperalgesic effectiveness suggesting T1AM as a potential treatment as a "pro-drug" for memory dysfunction in neurodegenerative diseases.


Coexistence of aplasia cutis and nevus psiloliparus--report of a novel case.
Nevus psiloliparus is a type of mesodermal nevus of the scalp classically seen with encephalocraniocutaneous lipomatosis. The close association between nevus psiloliparus and aplasia cutis congenita is called didymosis aplasticopsilolipara. Although typically associated with neurologic, ocular, and skeletal findings, didymosis aplasticopsilolipara can be seen without the context of encephalocraniocutaneous lipomatosis.


Gender abuse, depressive symptoms, and HIV and other sexually transmitted infections among male-to-female transgender persons: a three-year prospective study.
We examined gender abuse and depressive symptoms as risk factors for HIV and other sexually transmitted infections (HIV/STI) among male-to-female transgender persons (MTFs). We conducted a 3-year prospective study of factors associated with incident HIV, syphilis, hepatitis B, chlamydia, and gonorrhea among 230 MTFs from the New York Metropolitan Area. Statistical techniques included Cox proportional hazards analysis with time varying covariates. Among younger MTFs (aged 19-30 years), gender abuse predicted depressive symptoms (Center for Epidemiologic Studies Depression score ≥ 20), and gender abuse combined with depressive symptoms predicted both high-risk sexual behavior (unprotected receptive anal intercourse) and incident HIV/STI. These associations were independent of socioeconomic status, ethnicity, sexual orientation, hormone therapy, and sexual reassignment surgery. Gender abuse is a fundamental distal risk factor for HIV/STI among younger MTFs. Interventions for younger MTFs are needed to reduce the psychological impact of gender abuse and limit the effects of this abuse on high-risk sexual behavior. Age differences in the impact of gender abuse on HIV/STI suggest the efficacy of peer-based interventions in which older MTFs teach their younger counterparts how to cope with this abuse.


Comparative Analysis of Lateral Pharyngoplasty and Uvulopalatopharyngoplasty Techniques With Polisomnography and Epworth Sleepiness Scales.
Snoring is caused by the vibration of structures of the oral cavity, such as the soft palate, uvula, tonsils, base of the tongue, epiglottis, and lateral pharyngeal walls. When these structures collapse and obstruct the airway, apnea occurs. Obstructive sleep apnea syndrome (OSAS) is characterized by repeated periods of upper airway obstruction, a decrease in arterial oxygen saturation, and interrupted sleep. The prevalence of OSAS is 1% to 5% in men and 1.2% to 2.5% in women. Crucial factors in deciding the surgical approach include a detailed ear-nose-throat examination, Muller maneuver, sleep endoscopy, and apnea hypopnea index scores. Accepted treatments include continuous positive airway pressure (CPAP), surgeries of the base of the tongue and/or palate, and multi-level surgeries. It, however, is important to continue to evaluate the efficacies of such procedures. The authors evaluated the outcomes of 23 patients who underwent surgery for OSAS, using preoperative and postoperative polysomnography (PSG) and the Epworth sleepiness scale (ESS). The results were compared before and after surgery. In all, 14 patients had lateral pharyngoplasty and 9 had uvulopalatopharyngoplasty (UPPP). The PSG and Epworth scale values were significantly lower in both groups, postoperatively. Patients indicated that their quality of life had improved. In conclusion, the surgeries were successful. In line with the literature, our results indicate that lateral pharyngoplasty and UPPP can be used in appropriate patients. Longer-term studies on more patients will provide more detailed information in the future.


Activated carbon catalyzed persulfate oxidation of Azo dye acid orange 7 at ambient temperature.
Persulfate (PS) oxidative degradation of azo dye acid orange 7 (AO7) in an aqueous solution was studied in the presence of suspended granular activated carbon (GAC) at ambient temperature (e.g., 25°C). It was observed that there existed a remarkable synergistic effect in the GAC/PS combined system. Higher PS concentration and GAC dosage resulted in higher AO7 degrading rates. Near-neutral was the optimal initial pH. Adsorption had an adverse effect on AO7 degradation. AO7 had not only a good decolorization, but a good mineralization. The decomposition of PS followed a first-order kinetics behavior both in the presence and in the absence of AO7. Radical mechanism was studied and three radical scavengers (methanol (MA), tert-butanol (TBA), phenol) were used to determine the kind of major active species taking part in the degradation of AO7 and the location of degradation reaction. It was assumed that the degradation of AO7 did not occur in the liquid phase, but in the porous bulk and boundary layer on the external surface of GAC. SO(4)(-•) or HO•, generated on or near the surface of GAC, played a major role in the AO7 degradation. Finally, the recovery performance of GAC was studied through the GAC reuse experiments.


Mitochondrial thymidine kinase and the enzymatic network regulating thymidine triphosphate pools in cultured human cells.
In non-proliferating cells mitochondrial (mt) thymidine kinase (TK2) salvages thymidine derived from the extracellular milieu for the synthesis of mt dTTP. TK2 is a synthetic enzyme in a network of cytosolic and mt proteins with either synthetic or catabolic functions regulating the dTTP pool. In proliferating cultured cells the canonical cytosolic ribonucleotide reductase (R1-R2) is the prominent synthetic enzyme that by de novo synthesis provides most of dTTP for mt DNA replication. In non-proliferating cells p53R2 substitutes for R2. Catabolic enzymes safeguard the size of the dTTP pool: thymidine phosphorylase by degradation of thymidine and deoxyribonucleotidases by degradation of dTMP. Genetic deficiencies in three of the participants in the network, TK2, p53R2, or thymidine phosphorylase, result in severe mt DNA pathologies. Here we demonstrate the interdependence of the different enzymes of the network. We quantify changes in the size and turnover of the dTTP pool after inhibition of TK2 by RNA interference, of p53R2 with hydroxyurea, and of thymidine phosphorylase with 5-bromouracil. In proliferating cells the de novo pathway dominates, supporting large cytosolic and mt dTTP pools, whereas TK2 is dispensable, even in cells lacking the cytosolic thymidine kinase. In non-proliferating cells the small dTTP pools depend on the activities of both R1-p53R2 and TK2. The activity of TK2 is curbed by thymidine phosphorylase, which degrades thymidine in the cytoplasm, thus limiting the availability of thymidine for phosphorylation by TK2 in mitochondria. The dTTP pool shows an exquisite sensitivity to variations of thymidine concentrations at the nanomolar level.


Interactions of interleukin-1 with neurotrophic factors in the central nervous system: beneficial or detrimental?
Interleukin (IL)-1 is a multifunctional cytokine that plays a key role in mediating inflammation in the brain. Many different cell types in the brain express the IL-1 receptor and respond to this cytokine by activating cell-type-specific signaling pathways leading to distinct functional responses, which collectively comprise the inflammatory response in the brain. One key effect of IL-1 in the brain is the induction of trophic factor production by glial cells, which has traditionally been considered a neuroprotective response to injury or disease. However, recent studies have shown that nerve growth factor, which is regulated by IL-1, can induce neuronal survival or apoptosis via different receptors. This article examines the interaction of IL-1 with different trophic factors in the brain.


Folate status and folate related anemia: a comparative cross-sectional study of long-term care and post-acute care psychogeriatric patients.
Aging is associated with increased risk of anemia, poor nutrition, chronic illness, and impaired folate status. We aimed to investigate and compare folate status in long-term care psychogeriatric patients (LTCPP) and in post-acute care psychogeriatric patients (PACPP). This is a cross-sectional study conducted in a psychogeriatric medical center with long-term care and post-acute care wards. A total number of 553 LTCPP and 373 PACPP were studied. Low serum folic acid levels were found in 10% of LTCPP and in 13% of PACPP. Folic acid anemia (FAA) was found in 67% of LTCPP and 87% of PACPP (P = 0.046) with low serum folate levels. Mean levels of serum folate were similar but red blood cells folate (RBC-folate) was higher in PACPP (P = 0.025) and in males compared with women (P = 0.009). 56% of PACPP and 68% of LTCPP who had folic acid anemia presented with another type of anemia. Anemia of chronic disease was the most frequent coexisting anemia and was found in 65% of LTCPP and 52% of PACPP, followed by B12 deficiency anemia and iron deficiency anemia. We conclude that PACPP represent only a slightly different group, compared with LTCPP, with regard to the folate status. These high rates of folate and RBC-folate deficiencies, as well as of FAA and coexisting anemia, call for a routine evaluation of folate status in all psychogeriatric patients, whether LTCPP or PACPP.


The allogeneic effect in inbred mice. IV. Regulatory influences of graft-vs.-host reactions on host T lymphocyte functions.
The studies presented herein were designed to directly evaluate the effects of a transient GVH reaction on T lymphocyte functions. To this end, we have shown that generation of carrier-specific helper cell function can be significantly influenced by the allogeneic effect. Thus, carrier-primed helper cells derived from CAF(1) donor mice were generally much more active in specifically cooperating with syngeneic 2,4-dinitrophenyl (DNP)-primed B cells in adoptive recipients when parental A strain lymphocytes had been administered at some time during the priming regimen. This was true when allogeneic cells were administered concomitantly with the initial priming dose of carrier protein as well as when the GVH was induced in animals that had been exposed to antigen several days previously. This indicates that the allogeneic enhancing effects can be manifested on either primed or unprimed T cell populations. The ultimate effect of the GVH reaction on the development of helper T cell activity was found to be related to the number of allogeneic cells employed and the duration of the resultant GVH reaction in the carrier-primed host animal. Hence, allogeneic stimulation of slightly greater magnitude and/or longer duration resulted in marked suppression rather than enhancement of helper cell function in such donor mice. These findings may have general relevance to problems in autoimmune diseases and tumor immunity.


Nurr1 deficiency predisposes to lactacystin-induced dopaminergic neuron injury in vitro and in vivo.
Parkinson's disease (PD) has been proposed to result from a combination of genetic susceptibility and environmental exposure. Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in neuron degeneration and in pathogenesis of PD. Nurr1, a member of nuclear receptor superfamily, is a potential susceptibility gene for PD. In this in vitro and in vivo study, we investigated whether Nurr1 deficiency may predispose to environmental proteasome inhibitors-induced neuron injury. We found that lactacystin, an irreversible proteasome inhibitor, caused greater injury to SH-SY5Y cells that Nurr1 expression has been suppressed by small interference RNA (siRNA). On the contrary, the Nurr1 overexpressed SH-SY5Y cells by Nurr1 expression vector transfection rescued the lactacystin-induced injury. In vivo, stereotactic microinjection with lactacystin into right median forebrain bundle (MFB) of mice caused significant inhibition of the proteasome activity in both Nurr1 knock out heterozygous (Nurr1 +/-) mice and their littermate wild-type (Nurr1 +/+) mice. At same time, we found that there was a severer loss of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) and greater reduction of striatal dopamine (DA) levels in Nurr1 +/- mice as compared with that in Nurr1 +/+ mice. Furthermore, lactacystin-induced increase of cleaved PARP, cleaved caspase3 and p53 and decrease of bcl-2 in SN was significantly enhanced in Nurr1 +/- mice. These findings suggest that reduction in Nurr1 expression increases susceptibility to DAergic neuron injury induced by UPS impairment.


Pathology medical manpower planning in New Zealand results of 1977 survey.
As part of Medical Manpower Planning in New Zealand, a survey conducted by the New Zealand Society of Pathologists in association with the Royal College of Pathologists of Australia shows that at present there are 116 pathologists practising in New Zealand, a ratio of one to 27 000 population. This is far short of the requirement of 1:20 000, for which an additional 40 pathologists is required now, with an average annual requirement of 11 additional pathologists over the next nine years.


Identification and Pleiotropic Effect Analysis of GSE5 on Rice Chalkiness and Grain Shape.
Chalkiness is one of several major restricting factors for the improvement of rice quality. Although many chalkiness-related quantitative trait loci have been mapped, only a small number of genes have been cloned to date. In this study, the candidate gene GSE5 of a major quantitative trait locus (QTL) for rice chalkiness, qDEC5, was identified by map-based cloning. Phenotyping and haplotype analysis of proActin:GSE5 transgenic line, gse5-cr mutant, and 69 rice varieties further confirmed that GSE5 had the pleiotropic effects and regulated both chalkiness and grain shape. Genetic analysis showed GSE5 was a dominant gene for grain length and a semi-dominant gene for grain width and chalkiness. The DNA interval closely linked to GSE5 was introgressed to Zhenshan 97B (ZB) based on molecular marker-assisted selection, and the improved ZB showed lower chalkiness and longer but smaller grains, which showed that GSE5 played an important role in breeding rice varieties with high yield and good quality. Transcriptomics, proteomics, and qRT-PCR analyses showed that thirty-nine genes associated with carbon and protein metabolism are regulated by GSE5 to affect the formation of chalkiness, including some newly discovered genes, such as OsCESA9, OsHSP70, OsTPS8, OsPFK04, OsSTA1, OsERdj3A, etc. The low-chalkiness lines showed higher amino sugar and nucleotide sugar metabolism at 10 days after pollination (DAP), lower carbohydrate metabolism at 15 DAP, and lower protein metabolism at 10 and 15 DAP. With heat shock at 34/30°C, rice chalkiness increased significantly; OsDjC10 and OsSUS3 were upregulated at 6 and 12 DAP, respectively, and OsGSTL2 was downregulated at 12 DAP. Our results identified the function and pleiotropic effects of qDEC5 dissected its genetic characteristics and the expression profiles of the genes affecting the chalkiness formation, and provided a theoretical basis and application value to harmoniously pursue high yield and good quality in rice production.


Risk factors for anal sphincter tear during vaginal delivery.
To identify risk factors associated with anal sphincter tear during vaginal delivery and to identify opportunities for preventing this cause of fecal incontinence in young women. We used baseline data from two groups of women who participated in the Childbirth and Pelvic Symptoms (CAPS) study: those women who delivered vaginally, either those with or those without a recognized anal sphincter tear. Univariable analyses of demographic and obstetric information identified factors associated with anal sphincter tear. We calculated odds ratios (ORs) for these factors alone and in combination, adjusted for maternal age, race, and gestational age. We included data from 797 primaparous women: 407 with a recognized anal sphincter tear and 390 without. Based on univariable analysis, a woman with a sphincter tear was more likely to be older, to be white, to have longer gestation or prolonged second stage of labor, to have a larger infant (birth weight/head circumference), or an infant who was in occiput posterior position, or to have an episiotomy or operative delivery. Logistic regression found forceps delivery (OR 13.6, 95% confidence interval [CI] 7.9-23.2) and episiotomy (OR 5.3, 95% CI 3.8-7.6) were strongly associated with a sphincter tear. The combination of forceps and episiotomy was markedly associated with sphincter tear (OR 25.3, 95% CI 10.2-62.6). The addition of epidural anesthesia to forceps and episiotomy increased the OR to 41.0 (95% CI 13.5-124.4). Our results highlight the existence of modifiable obstetric interventions that increase the risk of anal sphincter tear during vaginal delivery. Our results may be used by clinicians and women to help inform their decisions regarding obstetric interventions. II.


In-Sio(2) cermet films for optical recording.
In-SiCO(2) cermet films have been studied as optical recording media in metal film ablation memory. Specular surfaces and the minimum writing threshold laser power have been obtained in SiO(2) 40-60-vol.% composition. Pit formation processes have been studied by the temperature bias method, and the use of a trigger layer has been proposed for decreasing the writing laser power. Bi-Pb-Sn-In eutectic alloy and SiO(2) cermet film have also been examined. The 35-mJ/cm(2) writing threshold laser energy was obtained in this cermet and the phthalocyanine trigger layer construction. Cermet films are stable up to 500 degrees C and are also stable in water.


Activity Enhancement of Ferrierite in Dimethyl Ether Carbonylation Reactions through Recrystallization with Sodium Oleate.
Methyl acetate (MA) has a wide range of applications as an important industrial chemical. Traditional MOR zeolite for carbonylation of DME to MA accumulated carbon easily because of a 12-membered ring (12 MR) channel. In this work, we innovatively developed the method of recrystallization ferrierite (FER) zeolite using special chelating ligand sodium oleate which can affect ions other than alkali metals. The characterization results of N2 adsorption, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR) show that hydrothermal recrystallization of ferrierite using sodium oleate resulted in a higher Si/Al ratio, a bigger specific surface area and a larger number of Brønsted acid sites in the eight MR channels, which was more efficient in the reaction of carbonylation of dimethyl ether than ordinary alkali treatment.


Case of harlequin ichthyosis with a favorable outcome: Early treatment and novel, differentially expressed, alternatively spliced transcripts of the ATP-binding cassette subfamily A member 12 gene.
Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, with a high mortality rate. Recent advances in neonatal care and the early administration of retinoids have improved the survival rate of HI. Here, we present a case of HI who was successfully treated with early administration of etretinate and showed good prognosis. Next-generation sequencing identified novel mutations of the ATP-binding cassette subfamily A member 12 gene (ABCA12), c.5884+4_+5delAA and c.7239G>A, which caused skipping of exons 39 and 48, respectively. Transcripts with exon 48 skipping, which cause a deletion in the second ATP-binding cassette of ABCA12, were dominantly expressed in the skin. Besides the early administration of etretinate, the differential expression of the mutant protein with limited segmental deletion of ABCA12 may be related to the favorable outcome of our patient.


Cardio-respiratory emergency: synoptic table for immediate diagnosis and action.
A new table on "Cardio-respiratory emergency," was designed for use mainly by occasional casualty doctors. It is printed in two colours, separating the diagnostic and therapeutic features. The general lay-out is from the top downward according to ABC sequence, and from the left to the right according to graduation. Also different varieties of shock are included in the table. A list with explaining key words is at the bottom of the table.


Genome instability in ataxia telangiectasia (A-T) families: camptothecin-induced damage to replicating DNA discriminates between obligate A-T heterozygotes, A-T homozygotes and controls.
Previously we used the topoisomerase I inhibitor camptothecin (CPT), which kills mainly S-phase cells primarily by inducing double strand breaks (DSBs) in replication forks, to show that ataxia telangiectasia (A-T) fibroblasts are defective in the repair of this particular subclass of DSBs. CPT treated A-T cells reaching G2 have abnormally high levels of chromatid exchanges, viewed as prematurely condensed G2 chromosomes (G2 PCC), compared with normal cells where aberrations are mostly chromatid breaks. Here we show that A-T lymphoblastoid cells established from individuals with different mutations in the ATM gene also exhibit increased levels of chromosomal exchanges in response to CPT, indicating that the replication-associated DSBs are misrepaired in all these cells. From family studies we show that the presence of a single mutated allele in obligate A-T heterozygotes leads to intermediate levels of chromosomal exchanges in CPT-treated lymphoblastoid cells, thus providing a functional and sensitive assay to identify these individuals.


Generation of leukotrienes from fetal and neonatal porcine blood vessels.
Various blood vessels from fetal and neonatal piglets were challenged with calcium ionophore A23187, to examine the release of leukotriene-like material. All tissues released as much or more leukotriene (LT) than adult porcine tissues previously examined. The release fell with increasing gestational age. The release from the intra-abdominal umbilical vein at 11 days preterm (480 ng of LTD4-like activity per gram of tissue) was an order of magnitude higher than that previously observed. The implications with regard to control of the fetal circulatory pattern are discussed.


Adaptability of non-genetic diversity in bacterial chemotaxis.
Bacterial chemotaxis systems are as diverse as the environments that bacteria inhabit, but how much environmental variation can cells tolerate with a single system? Diversification of a single chemotaxis system could serve as an alternative, or even evolutionary stepping-stone, to switching between multiple systems. We hypothesized that mutations in gene regulation could lead to heritable control of chemotactic diversity. By simulating foraging and colonization of E. coli using a single-cell chemotaxis model, we found that different environments selected for different behaviors. The resulting trade-offs show that populations facing diverse environments would ideally diversify behaviors when time for navigation is limited. We show that advantageous diversity can arise from changes in the distribution of protein levels among individuals, which could occur through mutations in gene regulation. We propose experiments to test our prediction that chemotactic diversity in a clonal population could be a selectable trait that enables adaptation to environmental variability.


Tuberculosis in Philippine National World War II Veterans immigrating to Hawaii, 1992-1993.
The Immigration Act of 1990* allows World War II veterans who are Philippine nationals to be naturalized as U.S. citizens and to enter the United States without any medical screening or restrictions. Following the diagnosis of tuberculosis (TB) in February 1992 in a Philippine national veteran who had recently arrived in Hawaii, the Hawaii Department of Health (HDOH) initiated efforts to assist veterans who had already arrived in Hawaii to receive TB testing and appropriate treatment and monitoring. This report describes the first case of TB identified in a veteran who entered Hawaii from the Philippines under this act and summarizes efforts by HDOH to detect and treat TB among Philippine national veterans.


Photosynthesis in Rhodospirillum rubrum. I. Autotrophic carbon dioxide fixation.
The incorporation and distribution of activity from (14)CO(2) was investigated under autotrophic conditions in the facultative photoautotroph, Rhodospirillum rubrum, with cells cultured on hydrogen, carbon dioxide, and ammonium sulfate. In 1 second (14)CO(2) fixation experiments essentially all of the activity was found in 3-phosphoglyceric acid: plotted against time percent incorporation into phosphate esters has a strikingly negative slope. These results suggest that under autotrophic conditions the reductive pentose phosphate cycle or the key reactions of the cycle play a major role in carbon metabolism in this photosynthetic bacterium. Incorporation into amino acids and into intermediates of the tricarboxylic acid cycle was quite low.


Relationship between visfatin and some clinical and biochemical parametres in peritoneal dialysis patients.
To characterise the relationship between visfatin levels and various clinical and biochemical parameters in peritoneal dialysis patients. The case-control study was conducted at the Medical Faculty Hospital, Yuzuncu Yil University, Van, Turkey, between May 2007 and December 2008, and involving 41 patients on peritoneal dialysis, 20 haemodialysis patients and 20 healthy controls. Fasting visfatin level was measured with enzyme-linked immunosorpent assay (ELISA) method, and patients on peritoneal dialysis were separated into two groups according to the visfatin levels - high and low. The groups were compared in terms of some clinical (height, weight, body mass index, waist circumference, hip circumference, waist/hip ratio, heart rate, systolic and diastolic blood pressure and the kt/V and CrCI (creatanine clearance) parameters which are indicative of the dialysis adequacy) and biochemical parameters (glucose, triglycerides, cholesterol, low density lipoprotein, high density lipoprotein, aspartate aminotransferase, alanine transminase, blood urea nitrogen, creatinine, total protein, albumin, globulin, sodium, potassium, magnesium, calcium, phosphorus, ferritin, venous blood gas, parathyroid hormone and insulin). SPSS 15 was used for statistcal analysis. No statistically significant difference in the visfatin levels was found between the patients and controls (7.71 +/- 4.04, 7.36 +/- 3.71, 7.70 +/- 1.61, respectively, p = 0.63). The triglyceride level of the high-visfatin group was significantly higher than that of the low-visfatin group (243.8 +/- 133.2, 150.8 +/- 65.8, respectively, p<0.05). However, there was no correlation between visfatin and triglyceride levels. No difference in the other clinical and biochemical parametres was observed between the two groups of peritoneal dialysis patients. No significant difference in the serum visfatin levels of peritoneal dialysis patients compared to haemodialysis patients or healthy individuals was noticed. Further studies are needed to confirm the effect of visfatin on triglyceride levels, and, if confirmed, the mechanism of this relation.


Prognostic value of cardiotocographic acoustic test in post-term pregnancies.
The aim of the study was to evaluate the prognostic value of the acoustic test in post-term pregnancies. 80 acoustic tests were done (alkaline phosphatase and oxytocinase). In 12 cases, the cardiotocographic recordings of the acoustic test were described as incorrect, 11 neonates of this were born in asphyxia. In the group of neonates responding to the stimulus correctly, all neonates were born in a generally good state. The results show that the acoustic test is characterized by high prognostic value and a correct test result can predict a good fetal state.


Current state of research on the clinical benefits of herbal medicines for non-life-threatening ailments.
Herbal medicines are becoming increasingly popular among patients because they are well tolerated and do not exert severe side effects. Nevertheless, they receive little consideration in therapeutic settings. The present article reviews the current state of research on the clinical benefits of herbal medicines on five indication groups, psychosomatic disorders, gynecological complaints, gastrointestinal disorders, urinary and upper respiratory tract infections. The study search was based on the database PubMed and concentrated on herbal medicines legally approved in Europe. After applying defined inclusion and exclusion criteria, 141 articles were selected: 59 for psychosomatic disorders (100% randomized controlled trials; RCTs), 20 for gynecological complaints (56% RCTs), 19 for gastrointestinal disorders (68% RCTs), 16 for urinary tract infections (UTI, 63% RCTs) and 24 for upper respiratory tract infections (URTI) (79% RCTs). For the majority of the studies, therapeutic benefits were evaluated by patient reported outcome measures (PROs). For psychosomatic disorders, gynecological complaints and URTI more than 80% of the study outcomes were positive, whereas the clinical benefit of herbal medicines for the treatment of UTI and gastrointestinal disorders was lower with 55%. The critical appraisal of the articles shows that there is a lack of high-quality studies and, with regard to gastrointestinal disorders, the clinical benefits of herbal medicines as a stand-alone form of therapy are unclear. According to the current state of knowledge, scientific evidence has still to be improved to allow integration of herbal medicines into guidelines and standard treatment regimens for the indications reviewed here. In addition to clinical data, real world data and outcome measures can add significant value to pave the way for herbal medicines into future therapeutic applications.


Drugs and breast-feeding.
(1) Report of severe adverse effects in infants from drugs passing into breast milk are rare. (2) Two reports of neurological disorders in infants due to doxepin, a tricyclic antidepressant, necessitating hospitalisation, serve as a reminder that this risk exists. (3) Epidemiological data are almost non existent. A prospective follow-up study of more than 800 breast-fed infants whose mothers were taking medicinal drugs showed minor adverse effects in 11% of the children (mainly diarrhoea, drowsiness and irritability). None of the mothers sought medical advice. (4) When a breast-feeding mother requires drug therapy, all available information should be weighed up before advising her to switch to bottle feeding.


Continuous infusion versus intermittent flushing to prevent loss of function of peripheral intravenous catheters used for drug administration in newborn infants.
The use of peripheral intravenous cannulae is common in newborn babies. Many of them require an intravenous line only for medications and not for fluid. Currently there is little uniformity in methods used to maintain cannula patency. The object of this review was to determine which method was better for maintaining intravenous lines used in neonates for intravenous medication only: intermittent flushing or continuous infusion We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), CINAHL (from 1982 to June 2004) and MEDLINE (from 1966 to June 2004) . Randomised controlled trials comparing continuous infusion to intermittent flushing to maintain patency of intravenous cannulas. Units of randomisation might include individual catheters or individual babies. Three reviewers independently assessed trial quality and extracted data. Two studies were eligible for inclusion. In one study only one of our primary outcomes was available: the duration of cannula patency for the first cannula used per infant was slightly longer in the continuous infusion group, but not significantly so, with a mean difference of -4.3 hours (95% CI -18.2 to 9.7). In the second study, only one of our primary outcomes was available: the mean (SD) number cannulas used per infant in the first 48 hours was less in the intermittent flush group with a mean difference of -0.76 cannulas (95% CI -1.37 to -0.15). No results were available for any of our other primary outcomes: in the published report, results were reported per catheter rather than per infant, a number of infants received more than one intravenous catheter (39 infants received an unknown number of catheters). The overall duration of cannula patency was significantly longer in the intermittent flush group with a mean duration of patency in the intermittent flush group of 2.1 days (SD 1.0) compared with the continuous infusion group where the mean duration of patency was 1.0 days (SD 0.5) - Student's t test P value 0.0003. It is difficult to draw reliable conclusions given the way the data were analysed and reported in the two included studies. The reliability of the results is uncertain. However, given the caution in interpreting these data, it should also be noted that the use of intermittent flushes was not associated in either study with a decreased cannula life or any other disadvantages, thus lending some support for the use of intermittent flushing of cannulas in a selected population in neonatal nurseries.


BRCA1 and BRCA2 mutations and treatment strategies for breast cancer.
Breast cancer is a global burden with a woman's lifetime risk of developing breast cancer at 1 in 8. Although breast cancer is a disease that affects mostly women, the lifetime risk in men is about 1 in 1000. Most cases of breast cancer are associated with somatic mutations in breast cells that are acquired during a person's lifetime. In this scenario, the mutations are not inherited and they do not cluster in families. In hereditary breast cancer, the specific genetic factors involved will determine the inherited cancer risk. Inherited mutations in the BRCA1 or BRCA2 genes have been well-described, but mutations in ATM, CDH1, CHEK2, PALB2, PTEN, STK11, and TP53 also confer breast cancer risk. Understanding the functional significance of hereditary mutations has opened new paths for breast cancer prevention and is uncovering promising treatment strategies.


Defining the role of pharmacists in medication-related genetic counseling.
There is little question that precision medicine will eventually be the standard of care in treatment with algorithms designed for therapy selection and is already being used in some specialties such as cystic fibrosis and multiple cancer treatments. Genetic counselors are the heart of the treatment team in relation to counseling regarding genetic risk factors and disease states. A framework for treatment within the interdisciplinary team with more defined roles and areas of specialty will need to be in place as this practice approach expands with new data and treatments. Pharmacists are poised to be of great assistance in this matrix as many of these roles are merely an extension of current tasks and responsibilities of pharmacy practice.


A combinatorial CRISPR-Cas12a attack on HIV DNA.
CRISPR-Cas12a is an alternative class 2 gene editing tool that may cause less off-target effects than the original Cas9 system. We have previously demonstrated that Cas12a attack with a single CRISPR RNA (crRNA) can neutralize all infectious HIV in an infected T cell line in cell culture. However, we demonstrated that HIV escapes from most crRNAs by acquisition of a mutation in the crRNA target sequence, thus providing resistance against Cas12a attack. Here, we tested the antiviral activity of seven dual crRNA combinations and analyzed the HIV proviral genomes for mutations at the target sites. We demonstrated that dual crRNA combinations exhibit more robust antiviral activity than a single crRNA attack and, more important, that the dual-crRNA therapy can prevent virus escape in long-term cultures. We confirmed the absence of any replication-competent virus in these apparently cured cultures. Surprisingly, we did not detect excision of the HIV sequences located between two Cas12a cleavage sites. Instead, we observed almost exclusively HIV inactivation by "hypermutation," that is, the introduction of indel mutations at both target sites due to the error-prone cellular DNA repair machinery.


[Probiotics and prebiotics for the prevention and treatment of atopic eczema].
The rapid increase of atopic diseases, particularly in western industrialized countries, demands comprehensive and cost-effective primary prevention. Existing findings regarding the use of probiotic lactic acid bacteria for the prevention of atopic eczema are promising. Therapeutic use appears to be more promising for infants with mild to moderate skin lesions and elevated immunoglobulin E levels than for older patients without any sensitization. Depending on the original bacterial count, prebiotics such as fructooligosaccharides and galactooligosaccharides cause an increase of bifidobacteria within the colon. The benefit of this increase in bifidobacteria in allergic diseases is unclear. In patients with atopic eczema a correlation was shown between the amount of bifidobacteria and the severity of atopic eczema.


[Effect of Prostanorm on the persistent potential of microorganisms isolated from patients with chronic bacterial prostatitis].
To determine the effect of the Prostanorm on the persistent potential of microorganisms isolated from the prostatic secretion of patients with chronic bacterial prostatitis. In vitro experiments were carried out on uropathogens, isolated from prostate secretions in patients with chronic bacterial prostatitis, including Escherichia coli, Staphylococcus aureus, S. haemolyticus, S. epidermidis, Enterococcus faecalis. The effect of Prostanorm (liquid extract for oral use) of NPO FarmVILAR (Russia) on the anti-cytokine activity of bacteria against regulatory cytokines (IL4, IL6, IL8, TNF and IL17A) was evaluated by enzyme immunoassay, while anti-lysozyme trait and the ability to form biofilms was evaluated by the photometric method. Inhibitory effect of Prostanorm on the anti-lysocyme activity and the ability of microorganisms to form biofilms was found. A decrease in the anticytokine activity against IL17A and TNFa in all studied species of microorganisms was seen, including anticytokine activity against IL4, IL6, IL8 in Escherichia coli and against IL6 and IL8 in coagulase-negative staphylococci. The ability of Prostanorm to reduce the persistence factors of opportunistic microorganisms in vitro is one of the possible mechanisms, proving its prostatotropic action, bacteriostatic and anti-inflammatory activity.


Echinoderm calcite: single crystal or polycrystalline aggregate.
Electron microscopy of natural and broken surfaces of echinoid skeletal plates reveals that the interior portions have the morphology of a single crystal, whereas the exterior is a polycrystalline aggregate with preferred orientation. These data help to resolve earlier contradictory x-ray and optical evidence.


Directed Evolution of a Panel of Orthogonal T7 RNA Polymerase Variants for in Vivo or in Vitro Synthetic Circuitry.
T7 RNA polymerase is the foundation of synthetic biological circuitry both in vivo and in vitro due to its robust and specific control of transcription from its cognate promoter. Here we present the directed evolution of a panel of orthogonal T7 RNA polymerase:promoter pairs that each specifically recognizes a synthetic promoter. These newly described pairs can be used to independently control up to six circuits in parallel.


Building the learning health system: Describing an organizational infrastructure to support continuous learning.
Academic health centers are reorganizing in response to dramatic changes in the health-care environment. To improve value, they and other health systems must become a learning health system, specifically one that has the capacity to understand performance across the continuum of care and use that information to achieve continuous improvements in efficiency and effectiveness. While learning health system concepts have been well described, the practical steps to create such a system are not well defined. Establishing the necessary infrastructure is particularly challenging at academic health centers due to their tripartite missions and complex organizational structures. Using an evidence-based framework, this article describes a series of organizational-level interventions implemented at an academic health center to create the structures and processes to support the functions of a learning health system. Following implementation of changes from 2008 to 2013, system-level performance improved in multiple domains: patient satisfaction, population health screenings, improvement education, and patient engagement. This experience can be applied to health systems that wrestle with making system-level change when existing cultures, structures, and processes vary. Using an evidence -based framework is useful when developing the structures and processes that support the functions of a learning health system.


Differentiation and limited proliferation of isolated Leishmania mexicana amastigotes at 27 degrees C.
We have demonstrated here that while many amastigotes of both Leishmania mexicana amazonensis and Leishmania mexicana mexicana differentiate to promastigotes when placed in culture at 27 degrees C, many others remain as amastigotes in their proliferative cycle. We have used this system to examine the effects of the anti-leishmanial compounds amphotericin B, 4-pentenoate and sodium stibogluconate (Pentostam) on the proliferation and differentiation of isolated extracellular amastigotes. Amphotericin B and 4-pentenoate showed little preferential effect on amastigote proliferation over promastigote proliferation although Leishmania mexicana mexicana (strain M379) was generally more resistant to these compounds than Leishmania mexicana amazonensis (strain LV78). This relative resistance was also observed in axenic cultures of proliferating promastigotes. L.m. mexicana amastigote differentiation was inhibited by amphotericin B and 4-pentenoate. Pentostam displayed a greater effect on amastigote differentiation than proliferation in both sub-species although again, a higher concentration was required to produce the same effect in L.m. mexicana.


High [18F]-fluorodeoxyglucose uptake in abdominal abscesses: a PET study.
We report two cases of abdominal abscess displaying high uptake of [18F]fluorodeoxyglycose (FDG) by positron emission tomography (PET). Abdominal abscesses should be considered in the differential diagnosis of abdominal masses showing high FDG uptake in PET studies.


Spatiotemporal Patterns of the Use of Urban Green Spaces and External Factors Contributing to Their Use in Central Beijing.
Urban green spaces encourage outdoor activity and social communication that contribute to the health of local residents. Examining the relationship between the use of urban green spaces and factors influencing their utilization can provide essential references for green space site selection in urban planning. In contrast to previous studies that focused on internal factors, this study highlights the external factors (traffic convenience, population density and commercial facilities) contributing to the use of urban green spaces. We conducted a spatiotemporal analysis of the distribution of visitors in 208 selected green spaces in central Beijing. We examined the relationship between the spatial pattern of visitor distribution within urban green spaces and external factors, using the Gini coefficient, kernel density estimation, and geographical detectors. The results of the study were as follows. The spatial distribution of visitors within central Beijing's green spaces was concentrated, forming different agglomerations. The three examined external factors are all associated with the use of green spaces. Among them, commercial facilities are the important external factor associated with the use of green spaces. For the selection of sites for urban green spaces, we recommend consideration of external factors in order to balance urban green space utilization.


Preparation and chemical composition of the cell membranes of developmental reticulate forms of meningopneumonitis organisms.
The outer limiting membranes of developmental reticulate forms of the meningopneumonitis organism were purified by a combination of differential centrifugation, trypsin digestion, and sodium dodecyl sulfate treatment, and their physical and chemical properties were compared with those of outer envelopes of mature dense forms of this organism. Reticulate bodies were easily disrupted by short periods of sonic treatment and were lysed by trysin digestion, in contrast to the dense bodies which were resistant to these treatments. In electron micrographs, reticulate body membranes were seen as very thin, flattened structures, whereas dense-body envelopes showed folding rigid membranes. The results of chemical fractionation of (32)P-labeled purified preparations indicated that reticulate body membranes have smaller amounts of phospholipid, and are more dense than cell walls of the mature forms. The analysis of amino acid composition of reticulate body cell membranes showed that they do not contain cystine or methionine, both of which were found in cell walls of dense bodies. These results clearly show that there are significant differences in the chemical and physical properties of the outer envelopes of the developmental and mature forms of this organism.


Transcervical artificial insemination in dogs and cats: review of the technique and practical aspects.
The technique of transcervical catheterization for artificial insemination has gained practical importance over the last 3 and 1 decades in bitches and queens, respectively. The vagina of both species has a thickening of the dorsal aspect called dorsal medial fold, which restricts the lumen of the paracervix, making catheterization of the cervix difficult both with manual and endoscopic techniques. Manual catheters have been used initially in the bitch and are now gradually being replaced by rigid endoscopy through the adaptation of human cystoscopes and ureteroscopes. Cystoscopes provide excellent imaging of the vagina, but cervical catheterization is more difficult due to the oblique 30° viewing angle of its telescope and may not be long enough to catheterize large size bitches. Ureteroscopes allow an acceptable view of the vaginal mucosa and offer advantages such as the possibility to catheterize the cervix of bitches of all body sizes, manipulate the cervical tubercle when the external cervical os is not visible, offer a better visualization of the cervix using the shunt (a large Foley catheter which allows insufflation and distention of the vagina). Feline cervical catheterization has been achieved with three different types of catheters; the last one, developed following careful anatomical studies of how the feline vaginal lumen changes during estrus, allows cervical catheterization thanks to digital manipulation of the cervix through the rectum.


Progression of primary myelofibrosis to polycythemia vera: A case report.
This case report describes the progression of primary myelofibrosis (PMF) to polycythemia vera (PV), and discuss its potential mechanisms. The patient was admitted because of abdominal discomfort and enlarged spleen for 19 months. A case of PMF progressed to PV was retrospectively analyzed. There were 19 months between the diagnosis of PMF and PV. The JAK2 V617F mutation was positive before and after the diagnosis of PV; however, new chromosomal abnormalities were detected during the progression. For treatment of PMF, the danazol, calcitriol, and thalidomide were given. Then, the use of thalidomide and calcitriol was stopped, and hydroxyurea was started. For treatment of PV, interferon treatment was given, whereas hydroxyurea was continued. After 30 months of the progression (at the recent follow-up), this patient had no obvious symptoms or thrombosis. PMF rarely progresses to PV, however, the progression will significantly improve the quality of life and prognosis.


Saccharomyces as a vaccine against systemic candidiasis.
We have shown heat-killed Saccharomyces (HKY) is a protective vaccine against aspergillosis and coccidioidomycosis. To test the hypothesis that the efficacy of HKY- induced protection may be due to the cross-reactive antigens in the cell walls of the different fungi, we studied the effect of HKY against systemic candidiasis. Male CD-1 mice were given different regimens of HKY subcutaneously prior to intravenous challenge with Candida albicans. Compared to PBS controls, the administration of HKY (6 × 10(7)) 3, 4 or 6 times prolonged survival (all P < 0.05) and reduced fungal load in the kidney (all P < 0.05). An HKY dose of 1.2 × 10(8) given 4 times prolonged survival (P = 0.02), but showed dose-limiting toxicity. HKY given by an oral route, or by a subcutaneous route with alum as an adjuvant, did not improve survival. Overall, we found that HKY protects mice from infection by Candida albicans in a dose-and regimen-dependent manner. To understand the protection induced by HKY against different fungal species, additional studies of epitope mapping are warranted.


Latent-variable modeling of brain gray-matter volume and psychopathy in incarcerated offenders.
Advanced statistical modeling has become a prominent feature in psychological science and can be a useful approach for representing the neural architecture linked to psychopathology. Psychopathy, a disorder characterized by dysfunction in interpersonal-affective and impulsive-antisocial domains, is associated with widespread neural abnormalities. Several imaging studies suggest that underlying structural deficits in paralimbic regions are associated with psychopathy. Although these studies are useful, they make assumptions about the organization of the brain and its relevance to individuals displaying psychopathic features. Capitalizing on statistical modeling, in the present study (N = 254), we used latent-variable methods to examine the structure of gray-matter volume in male offenders, and assessed the latent relations between psychopathy and gray-matter factors reflecting paralimbic and nonparalimbic regions. Results revealed good fit for a 4-factor gray-matter paralimbic model and these first-order factors were accounted for by a superordinate paralimbic "system" factor. Moreover, a superordinate psychopathy factor significantly predicted the paralimbic, but not the nonparalimbic factor. The latent-variable paralimbic model, specifically linked with psychopathy, goes beyond understanding single brain regions within the system and provides evidence for psychopathy-related gray-matter volume reductions in the paralimbic system as a whole. (PsycINFO Database Record


The immunosuppressant rapamycin induces inactivation of p70s6k through dephosphorylation of a novel set of sites.
The immunosuppressant rapamycin selectively abolishes phosphorylation and activation of p70s6k/p85s6k at concentrations that either block or suppress cell growth. The four sites of phosphorylation associated with p70s6k/p85s6k activation all display Ser/Thr-Pro motifs and are closely clustered within a putative autoinhibitory domain of the enzyme. To produce a constitutively active, rapamycin-resistant form of the kinase, these four sites were converted to either Asp or Glu. When overexpressed in human 293 cells, the activity of the mutant is similar to that of the parent enzyme, under conditions where the parent is phosphorylated and active. Unexpectedly, however, the mutant remains sensitive to rapamycin and is inactivated in vitro by protein phosphatase 2A. Peptide maps reveal that rapamycin abolishes the activity of the overexpressed p70s6k through the dephosphorylation of a novel set of sites distinct from those associated with mitogenic activation.


[Myoepithelial carcinoma ex-pleomorphic adenoma of the parotid gland].
Myoepithelial carcinoma accounts for less than 1% of salivary gland malignant tumors. It may develop de novo or, in approximately 50% of the cases, from a pleomorphic adenoma. A 57-year-old man with a history of a pleomorphic adenoma of the parotid treated surgically 6 years earlier, presented with a 2 cm tumor mass, palpable in the scar region. The histological examination and immunohistochemical study revealed a low-grade myoepithelial carcinoma. The patient had no complementary treatment. He presented 5 years later with a 2 cm parapharyngeal recurrence which was resected. There was no evidence of recurrent tumor or of distant metastasis at 4 year follow-up. Although myoepithelial cells are often predominant in pleomorphic adenomas, carcinomas developing in pleomorphic adenomas show in most cases a glandular differentiation and myoepithelial carcinomas are rare. Currently the diagnostic criteria, the prognosis, and the management of myoepithelial carcinomas are not well documented. Invasive carcinomas developing in pleomorphic adenoma are known to be highly aggressive neoplasms and myoepithelial carcinomas ex-pleomorphic adenoma seem to have a better prognosis. Our reported case was characterized by the weak aggressiveness of the lesion.


Structured correlation in models for clustered data.
Correlation is always a concern in the analysis of clustered data. One area of interest is to develop a general correlation modelling approach for high dimensional data with unbalanced hierarchical and heterogeneous data structures, e.g. multilevel data. Commonly used correlation structures might have limitation for such situations. In this paper, we propose two extensions, multiblock and multilayer correlations. These methods are very flexible in modelling correlation and can be incorporated in many multivariate approaches, while the major discussion focuses on the applications under the generalized estimating equations (GEE) methods. The approaches are especially useful in GEE when each cluster is large and complex but the number of clusters is small. If an incorrect correlation is applied to such data, the results are less efficient. Multiblock and multilayer correlations extend GEE methods to model complicated multilevel data with arbitrary number of levels and cluster size. The extended estimating equation for correlation parameters has an orthogonal property, and the computation is very efficient. A simulation study compares the conventional methods versus the proposed methods, and it shows the gain in relative efficiency and the flexibility in modelling various structures.


Use of an anaerobic culture jar in processing pediatric throat cultures.
Two hundred consecutive throat cultures from a Pediatric Walk-in Clinic were processed, using both aerobic and anaerobic culture techniques. The 35 aerobic isolates of group A beta-hemolytic streptococci (BHS) were all confirmed anaerobically as well, and there were two additional isolates detected only by the anaerobic technique. Of these 37 bacitracin-sensitive isolates, only 24 (65%) could be identified at 24 hours using the aerobic technique, compared to 29 (78%) using the anaerobic technique. In contrast to this relatively small effect upon the isolation of group A BHS, the yield of BHS from groups B, C, F, and G was more than doubled by the anaerobic technique. The confusion engendered by the improved detection of these bacitracin-resistant BHS using the anaerobic technique offset the small advantage in thoroughness and speed of detection of group A organisms. On this account, until more is known about the possible significance of isolating nongroup A BHS in the pharynx, the advisability of using an anaerobic culture jar to process pediatric throat cultures remains uncertain.


Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration.
The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver.


Sweating responses to central and peripheral heating in spinal man.
Studies of central and peripheral heating of a resting spinal man (T6) were performed under various ambient temperatures (20-34 degrees C). It was found that at a constant core temperature, sweating could not be initiated by sentient skin heating alone, but skin cooling alone did produce a rapid decrease in sweating response. Central heating alone induced sweating responses and the central temperature thresholds of sweating were inversely related to the ambient (sentient skin) temperatures. The local and mean sweating rates were found to be linearly related to the core temperature. The slopes of local sweating rates versus the core temperature vary increasingly with the following locations: chest, forearm, and forehead; but the slopes of mean sweating rates versus core temperature were essentially constant.


Development of a criteria-based performance appraisal for emergency department staff nurses.
Developing a criteria-based performance appraisal tool is a rewarding effort, but not one to be taken lightly. It took weeks. At times, the project loomed as "mission impossible." A reflection of its success is the fact that other ED staff members (e.g., charge nurses, clerks, triageurs, and lab assistants) now want criteria-based performance appraisals for their positions. We have just finished a job description and criteria-based appraisal for laboratory assistants.


Biochemical relationships between bone turnover markers and blood glucose in patients with type 2 diabetes mellitus.
Patients with type 2 diabetes mellitus develop many complications including osteopenia, which is associated with high fracture risk. Osteocalcin is a non collagenous protein derived from the osteoblasts. Recently, it was found that osteocalcin enhances the pancreatic beta cell proliferation, insulin secretion and protection against type 2 diabetes. Investigation of the association of serum osteocalcin and other bone turnover markers with blood glucose level and diabetes mellitus duration in type 2 diabetic patients. Twenty diagnosed type 2 diabetic patients together with 20 healthy controls were enrolled in this study. Serum osteocalcin, alkaline phosphatase activity and calcium concentrations were measured by commercial ELISA kits. The results showed that type 2 diabetic patients exhibited a significantly lower serum osteocalcin and calcium (p=0.0001 and 0.002 respectively) and a higher alkaline phosphatase (p=0.008) compared to the controls. Multiple linear regression analysis revealed that serum osteocalcin was inversely associated with fasting blood glucose and Diabetes Mellitus duration (β=- 0.018; p=0.007 and β=- 0.085; p=0.014 respectively) in Type 2 diabetic patients. In addition, alkaline phosphatase was positively associated (β=0.828; p=0.015) while serum calcium was negatively associated (β=- 0.046; p=0.048) with Diabetes Mellitus duration. These results refer to the strong association between diabetes and bone turnover markers and call for monitoring of diabetes-associated osteopenia in type 2 diabetic patients.


Cryopreservation effects on intermediary metabolism in a pancreatic substitute: a (13)C nuclear magnetic resonance study.
Cryopreservation is important for clinical translation of tissue-engineered constructs. With respect to a pancreatic substitute, encapsulated islets or beta cells have been widely studied for the treatment of insulin-dependent diabetes mellitus. Besides cell viability loss, cryopreservation may affect the function of the remaining viable cells in a pancreatic substitute by altering fundamental processes in glucose-stimulated insulin secretion, such as pathways associated with intermediary metabolism, potentially leading to insulin-secretion defects. In this study, we used (13)C nuclear magnetic resonance (NMR) spectroscopy and isotopomer analysis to determine the effects of conventional freezing and ice-free cryopreservation (vitrification) on carbon flow through tricarboxylic acid (TCA) cycle-associated pathways in encapsulated murine insulinoma βTC-tet cells; the secretory function of the encapsulated cells postpreservation was also evaluated. Specifically, calcium alginate-encapsulated βTC-tet cells were frozen or vitrified with a cryoprotectant cocktail. Beads were warmed and (13)C labeling and extraction were performed. Insulin secretion rates were determined during basal and labeling periods and during small-scale glucose stimulation and K(+)-induced depolarization. Relative metabolic fluxes were determined from (13)C NMR spectra using a modified single pyruvate pool model with the tcaCALC modeling program. Treatments were compared with nonpreserved controls. Results showed that relative carbon flow through TCA-cycle-associated pathways was not affected by conventional freezing or vitrification. However, vitrification, but not freezing, led to impaired insulin secretion on a per viable cell basis. The reduced secretion from the Vitrified group occurred irrespective of scale and was present whether secretion was stimulated by glucose or K(+)-induced depolarization, indicating that it might be due to a defect in late-stage secretion events.


[Acute neuromyelitis optica and acute pulmonary tuberculosis (author's transl)].
A case of neuromyelitis optica and acute pulmonary tuberculosis in a 22 year old moroccan girl is reported. Regression of the medullary lesion and high level gamma globulin inflammatory CSF bring this case close to multiple sclerosis. The association with acute pulmonary tuberculosis suggest an acute demyelinisation caused by an immunologic reaction.


The anti-inflammatory activity of resveratrol in acute kidney injury: a systematic review and meta-analysis of animal studies.
Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of the evidence for this practice is unclear. This study investigated the effect of RSV on AKI and the underlying mechanism. We searched PubMed, EMBASE, and Web of Science from 2005 to April 2022 for controlled animal trials assessing the effect of conventional resveratrol versus placebo on renal function outcome after AKI. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42022329596. We retrieved 455 studies, 25 studies comprising data of 436 animals that met the inclusion criteria. Our meta-analysis suggested that RSV treatment was significantly associated with lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The greatest effects were recorded in low-dose (<20 mg/kg/day) groups rather than in high-dose (> 20 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of RSV can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of <2 weeks. This systematic review of animal AKI studies showed a consistently favourable effect of RSV as compared to placebo on renal function outcomes that increased with lower TNF-α, IL-6, and IL-1β. RSV has a more beneficial effect on SA-AKI animal models than the others. When the RSV intervention dose was low (< 20 mg/kg/day) and the intervention time was <2 weeks, more benefits could be observed.


[Cervical spondylosis].
Japan has now become an aging society. In 2014, people aged more than 65 years old accounted for 25.1% of Japan's entire population. Aging is associated with an increased risk of problems related to the locomotive organs. Deterioration of locomotive ability causes falls or tumbles, which would be a threat to good health and longevity of aged people. To maintain the locomotive ability of the elderly, therefore, the Japanese Orthopaedic Association starts a campaign to promote awareness and prevention of "locomotive syndrome". Cervical spondylosis is a disorder for age-related wear affecting the disks and vertebrae of cervical spine. It would also be a cause of "locomotive syndrome". Here, we give an outline of this disease and introduce its diagnosis and treatment.


Homology analysis and cross-immunogenicity of OmpA from pathogenic Yersinia enterocolitica, Yersinia pseudotuberculosis and Yersinia pestis.
The outer membrane protein A (OmpA) is one of the intra-species conserved proteins with immunogenicity widely found in the family of Enterobacteriaceae. Here we first confirmed OmpA is conserved in the three pathogenic Yersinia: Yersinia pestis, Yersinia pseudotuberculosis and pathogenic Yersinia enterocolitica, with high homology at the nucleotide level and at the amino acid sequence level. The identity of ompA sequences for 262 Y. pestis strains, 134 Y. pseudotuberculosis strains and 219 pathogenic Y. enterocolitica strains are 100%, 98.8% and 97.7% similar. The main pattern of OmpA of pathogenic Yersinia are 86.2% and 88.8% identical at the nucleotide and amino acid sequence levels, respectively. Immunological analysis showed the immunogenicity of each OmpA and cross-immunogenicity of OmpA for pathogenic Yersinia where OmpA may be a vaccine candidate for Y. pestis and other pathogenic Yersinia.


miR-409-3p Regulated by GATA2 Promotes Cardiac Fibrosis through Targeting Gpd1.
Cardiac fibrosis is a hallmark of numerous chronic cardiovascular diseases that leads to heart failure. However, there is no validated therapy for it. Dysregulation of microRNAs has been confirmed to be involved in cardiac fibrosis development. However, the regulatory network was not well explored. This study was the first to highlight the role and molecular mechanism of miR-409-3p in cardiac fibrosis. We found that miR-409-3p was consistently increased in three fibrotic models, including heart tissues of postmyocardial infarction (MI) mice and neonatal rat cardiac fibroblasts treated with angiotensin II (Ang II) or transforming growth factor-β (TGF-β). Furthermore, myocardial infarction surgery-induced cardiac fibrosis and dysfunction were attenuated by systemic delivery of miR-409-3p antagomir. Notably, transfection with miR-409-3p mimics promoted the proliferation of cardiac fibroblasts and fibroblast-to-myofibroblast differentiation, accompanied by upregulated expression of Col1a1, Col3a1, and α-SMA. On the contrary, the miR-409-3p inhibitor exhibited the opposite effect. Following this, we verified Gpd1 as a direct target of miR-409-3p. Gpd1 siRNA abolished the antifibrotic effect of miR-409-3p inhibitor in neonatal rat cardiac fibroblasts, suggesting that miR-409-3p promotes cardiac fibrosis at least partially through Gpd1. Moreover, GATA2 was identified as a cardiac fibrosis-associated upstream positive transcription factor of miR-409-3p. Finally, these findings suggest that modulating miR-409-3p could be a potential therapeutic method for cardiac fibrosis.


Automatic identification of bacterial types using statistical imaging methods.
The objective of the current study is to develop an automatic tool to identify microbiological data types using computer-vision and statistical modeling techniques. Bacteriophage (phage) typing methods are used to identify and extract representative profiles of bacterial types out of species such as the Staphylococcus aureus. Current systems rely on the subjective reading of profiles by a human expert. This process is time-consuming and prone to errors, especially as technology is enabling the increase in the number of phages used for typing. The statistical methodology presented in this work, provides for an automated, objective and robust analysis of visual data, along with the ability to cope with increasing data volumes.


The impact and mechanism of TET3 overexpression on the progression of hepatic fibrosis.
Aims: To investigate whether TET3 regulates hepatic stellate cell apoptosis and understand the role of demethylation in hepatic fibrosis (HF). Methods: LX-2T cells were infected with TET3 lentivirus. After TET3 adenovirus infection, the degree of HF in each group was analyzed. Chromatin immunoprecipitation was used to verify the targeting relationship between TET3 and CBP, and finally the expression of various proteins was detected. Results: TET3 overexpression activated the CBP/FOXO1-BIM pathway, increased the expression of apoptotic proteins and accelerated the apoptosis of activated LX-2 cells. The degree of HF was improved in the TET3 upregulation group. Conclusion: TET3 can activate the CBP/FOXO1-BIM pathway to accelerate the apoptosis of activated hepatic stellate cells and ultimately alleviate HF.


Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies.
Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally. We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes. The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar. Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery. Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth. The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account. Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size. The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.


Surgical repair for entire inferior vena cava occlusion in Budd-Chiari syndrome.
Successful repair of thrombotic occlusion of the entire inferior vena cava, including the iliac and hepatic veins, was performed on a 51-year-old man with Budd-Chiari syndrome associated with severe liver dysfunction.


Ion Transport Behaviors of Nanofluidic Diode Bichannel Systems in the Independent and Synergistic Cascade Mode.
The nanofluidic diode device was a significant ionic transistor. Its multiple cascades could realize diversified ion transport behaviors and information processing functions. Different cascade modes of channel units will affect the response current properties of multichannel systems. Inspired by independent and synergistic effects in semiconductor transistors, artificial conical nanoporous bichannel systems were investigated in separation and stacking cascade modes to discuss their different ion transport behaviors. The dynamic resistance fitting method was adopted to discuss the properties of each circuit components in the bichannel system for analyzing the circuit properties in different cascade modes. In the stacking mode, electric field interactions at the heterojunctions between channel units dominated the ionic transport properties, and response current of the bichannel system was influenced by the channel unit cascade sequence. In the separation mode, channel units transport ions independently, and the cascade sequence had little effect on response current properties of the system. These promising results provide a new strategy to design and build a series of artificial composite nanochannels with multifunction and intelligence.


Blockade of voltage-gated potassium channels ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro.
The voltage-gated potassium (Kv) channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) have shown beneficial effects on some neurological disorders. But their involvements in diabetes-associated cognitive dysfunction are still unknown. The present study aims to investigate whether the blockade of Kv channels by TEA and 4-AP alleviate cognitive decline in diabetes. In vivo, the effects of TEA and 4-AP (5 mg/kg body weight per day, 1 mg/kg body weight per day intraperitoneal injected for 4 weeks, respectively) were investigated in streptozotocin-induced C57BL/6 diabetic mice. In vitro study, we investigated the effects of TEA and 4-AP on the high glucose (HG) -stimulated primary cortical neurons. The results showed that TEA and 4-AP ameliorated the cognitive decline of diabetic mice in the Morris water maze test, improved the ultrastructure of pancreatic β cells, hippocampal neurons and synapses, decreased oxidative stress, modulated apoptosis-related proteins, and activated phosphatidylinositol 3-kinase (PI3K)/ Protein kinase-B (PKB or Akt) signaling pathway. In the HG-stimulated primary cultured cortical neurons, TEA and 4-AP increased the cell viability, decreased oxidative stress; prevented apoptosis and activated PI3K/Akt signaling pathway. Additionally, the PI3K inhibitor LY294002 partially abolished the effects of TEA and 4-AP. These findings indicate that the blockade of Kv channels by TEA and 4-AP ameliorates the diabetes-associated cognitive dysfunction via PI3K/Akt pathway, suggesting that targeting Kv channels could be a promising strategy for the treatments of cognitive impairments in diabetes.


[Changes in QT interval of electrocardiogram under +Gz acceleration and its significance].
To define whether QT interval could be used to predict the response of pilots to +Gz stress. 37 pilots underwent +4 Gz acceleration on a human centrifuge. According to their responses to +Gz stress, subjects were divided into group A (good reaction group, n=18), group B (hyperfunction reaction group, n=14) and group C (inhibition reaction group, n=1). QT and RR interval were measured pre-, during and post-G. The data of 33 subjects (89.2%) whose QT interval could be measured were analyzed statistically. During +Gz, QT and RR interval were shortened and sensitivity of QT interval to RR interval was augmented significantly (vs. pre-G, P<0.001); group B had higher sensitivity of QT interval to RR interval during +Gz (P<0.001, as compared with group A); discrimination functions established by QT and RR interval during +Gz were efficient and their accurate judgement rate was 81.8%. The changes in QT interval of ECG were related to autonomic nervous imbalance under +Gz; QT interval and RR interval could be used to predict the response of pilots to +Gz stress. These suggested that the parameters and method in this study might be used in G-LOC warning system.


A new equation set for converting body density to percent body fat.
One source of error in the underwater weighing (UWW) method of body fat determination is variability in bone mass as a fraction of total nonfat mass. We examined this error theoretically and experimentally using data gathered on 219 human subjects who were measured by UWW and also by the newer technique of dualenergy X-ray absorptiometry (DXA). The experimental data suggest an error was made in the assumed bone mass fraction used in the derivation of the Brozek equation, the standard means of converting the body density values obtained in UWW to body fat percent. Using this new experimental data, a new equation (set) is proposed for use in UWW measurements.


Increased formation of methylglyoxal and protein glycation, oxidation and nitrosation in triosephosphate isomerase deficiency.
Triosephosphate isomerase deficiency is associated with the accumulation of dihydroxyacetonephosphate (DHAP) to abnormally high levels, congenital haemolytic anaemia and a clinical syndrome of progressive neuromuscular degeneration leading to infant mortality. DHAP degrades spontaneously to methylglyoxal (MG)--a potent precursor of advanced glycation endproducts (AGEs). MG is detoxified to D-lactate intracellularly by the glyoxalase system. We investigated the changes in MG metabolism and markers of protein glycation, oxidation and nitrosation in a Hungarian family with two germline identical brothers, compound heterozygotes for triosephosphate isomerase deficiency, one with clinical manifestations of chronic neurodegeneration and the other neurologically intact. The concentration of MG and activity of glyoxalase I in red blood cells (RBCs) were increased, and the concentrations of D-lactate in blood plasma and D-lactate urinary excretion were also increased markedly in the propositus. There were concomitant increases in MG-derived AGEs and the oxidative marker dityrosine in hemoglobin. Smaller and nonsignificant increases were found in the neurologically unaffected brother and parents. There was a marked increase (15-fold) in urinary excretion of the nitrosative stress marker 3-nitrotyrosine in the propositus. The increased derangement of MG metabolism and associated glycation, oxidative and nitrosative stress in the propositus may be linked to neurodegenerative process in triosephosphate isomerase deficiency.


Mobility Enhancement in Graphene by in situ Reduction of Random Strain Fluctuations.
Microscopic corrugations are ubiquitous in graphene even when placed on atomically flat substrates. These result in random local strain fluctuations limiting the carrier mobility of high quality hBN-supported graphene devices. We present transport measurements in hBN-encapsulated devices where such strain fluctuations can be in situ reduced by increasing the average uniaxial strain. When ∼0.2% of uniaxial strain is applied to the graphene, an enhancement of the carrier mobility by ∼35% is observed while the residual doping reduces by ∼39%. We demonstrate a strong correlation between the mobility and the residual doping, from which we conclude that random local strain fluctuations are the dominant source of disorder limiting the mobility in these devices. Our findings are also supported by Raman spectroscopy measurements.


Effect of bovine respiratory syncytial virus infection on hypersensitivity to inhaled Micropolyspora faeni.
Respiratory syncytial virus causes mild-to-severe respiratory disease in human infants and young children; a closely related bovine respiratory syncytial virus causes a similar disease pattern in calves. Increased disease severity in atopic children suggests that allergic reactivity may enhance the severity of RSV-induced disease. To examine the association between bovine respiratory syncytial virus (BRSV) infection and allergic reactivity two groups of calves were exposed to aerosolized Micropolyspora faeni (Mf) during an experimental BRSV infection. One group exposed to Mf concurrent with BRSV was challenge-exposed to Mf while infected a second time with BRSV, while the other similarly sensitized and infected group was mock challenged. A control group was exposed only to Mf aerosol and another control group was infected with virus but not exposed to Mf aerosol. Parameters examined included: clinical signs, Mf-specific IgG and IgE, BRSV-specific antibody and IgE, leukotrienes C4 and B4 prostaglandins E2, F2 alpha and D2, and lung pathology. While the initial BRSV infection failed to enhance sensitization to inhaled Mf, a second BRSV infection exacerbated clinical signs resulting from Mf aerosol. Consideration of eicosanoid and antibody profiles together with clinical signs suggests that mechanisms of both type I and type III hypersensitivity were operative during Mf challenge of sensitized calves.


Insulin sensitivity, insulin secretion, and glucose tolerance versus intima-media thickness in nondiabetic postmenopausal women.
To study the association between insulin sensitivity and secretion vs. early manifestations of atherosclerosis, we performed a 5-yr prospective study in 84 nondiabetic, postmenopausal women, aged 58.7 +/- 0.4 yr (mean +/- SD). Insulin sensitivity was measured with the euglycemic, hyperinsulinemic clamp, and insulin secretion was measured as the acute response to iv arginine (5 g). Early atherosclerosis was studied by ultrasonography of the right carotid artery. Mean intima-media thickness (IMT), determined 1 cm proximal to the bifurcation, was 0.81 +/- 0.14 mm at baseline and increased by 0.012 +/- 0.014 mm/yr over the 5 yr (P < 0.001). The maximal IMT, determined in the carotid bifurcation, was 1.42 +/- 0.42 mm at baseline and increased by 0.035 +/- 0.049 mm/yr (P < 0.001). Neither basal IMT nor the increase in mean or maximal IMT correlated to insulin sensitivity or secretion. In contrast, both baseline IMT and the progression in IMT over the 5-yr follow-up (both mean common carotid artery IMT and maximal bifurcation IMT) correlated with systolic blood pressure and low-density lipoprotein cholesterol. We conclude that carotid intima-media thickness is not related to insulin sensitivity or secretion in nondiabetic, postmenopausal women. Instead, the strongest association is seen with systolic blood pressure and low-density lipoprotein cholesterol levels.


Successful Treatment of Pancreatic Fistula Following Surgery for Congenital Biliary Dilatation with Endoscopic Ultrasound-Guided Transduodenal Drainage.
Despite improvements in surgical techniques and perioperative management, postoperative pancreatic fistula (PF) is often difficult to treat and can be fatal due to various complications without effective drainage. Here, we report a case of PF following surgery for congenital biliary dilatation (CBD) successfully managed by endoscopic ultrasound (EUS)-guided transduodenal drainage. A 55-year-old woman underwent extrahepatic bile duct resection, including the gallbladder, and biliary tract reconstruction for CBD. On the 10th postoperative day (POD), computed tomography (CT) showed fluid retention observed from the upper edge of the pancreatic head to the surface of the right lobe of the liver. First, percutaneous fine-needle aspiration was performed on the fluid retention in the lateral part of the liver on the 11th POD. The amylase level in the drainage was high (30,156 U/L), and we diagnosed it as PF. Percutaneous drainage was difficult for fluid retention on the cut surface of the pancreas; thus, drainage under EUS guidance was decided. On the 13th POD, EUS was performed, a scan of the duodenal bulb revealed fluid retention with debris inside, and approximately 20-mL fluid was aspirated (amylase: 139,200 U/L). Although the inflammatory response temporarily improved, it recurred, so we decided to perform continuous drainage. On the 21st POD, EUS was performed again; a 19-G needle was used; a 0.025-in angle-type Jagwire was advanced into the fluid retention and expanded using a 7-Fr dilator; and then, a 6-Fr endoscopic nasoabscess drain (ENAD) tube was placed. On the 29th POD, CT showed that the fluid retention on the upper edge of the head of the pancreas had shrunk to a thickness of approximately 20 mm. On the 30th POD, the patient started eating. The ENAD tube was removed on the 38th POD. The patient was discharged from the hospital on the 45th POD without any symptoms. EUS-guided transduodenal drainage is an effective treatment option for postoperative PF following surgery for CBD.