Impact of a COPD care bundle on hospital readmission rates.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide and contributes considerably to morbidity and health care costs. In October 2014, the Centers for Medicare and Medicaid Services introduced financial penalties followed by bundled payments for care improvement initiatives in patients hospitalized with COPD. This study seeks to evaluate whether an evidence-based interprofessional COPD care bundle focused on inpatient, transitional, and outpatient care would reduce hospital readmission rates. A pre- and postintervention analysis comparing readmission rates after a hospitalization for COPD in subjects who received standard of care versus an interprofessional team-led COPD care bundle was conducted. The primary outcome was 30-day all-cause readmissions; secondary outcomes included 60- and 90-day all-cause readmissions, escalation of pharmacotherapy, interprofessional interventions, and hospital length of stay. A total of 189 subjects were included in the control arm and 127 subjects in the COPD care bundle arm. A reduction in 30-day all-cause readmissions between the control arm and COPD care bundle arm (21.7% vs. 11.8%, P = 0.017) was seen. Similar outcomes were seen in 60-day (18% vs. 8.7%, P = 0.013) and 90-day all-cause readmissions (19.6% vs. 4.7%, P < 0.001). Pharmacists consulted with 68.5% of subjects and assisted with access to outpatient medications in 45.7% of subjects in the COPD care bundle arm. An escalation in maintenance therapy occurred more often in the COPD care bundle arm (22.2% vs. 44.9%, P < 0.001) than the control arm. An interprofessional team-led COPD care bundle resulted in significant reductions in all-cause hospital readmissions at 30, 60, and 90 days.


Acidic phospholipids, diacylglycerols, and free fatty acids in gerbil brain: a comparison of ischemic changes resulting from carotid ligation and decapitation.
The levels of brain acidic phospholipids (poly-PI, PI, PA, and PS), DG, and FFA and their acyl group profiles were determined after induction of ischemia in gerbils by ligation of the common carotid arteries and decapitation. Ischemia induced by both procedures resulted in a significant decrease in poly-PI (20% for 1-min decapitation and 1-min ligation). Except for a 16% increase in PI in the 5-min decapitation group, no apparent change was found in other phospholipids after either ischemic condition. The level of DG was increased one- and three-fold after 1 and 5 min, respectively, of decapitative ischemic treatment. Ligation of the carotid arteries for 1 min resulted also in a one-fold increase in the DG level. The decapitative model resulted in a one- and five-fold increase in FFA level (with respect to 1 and 5 min, respectively), whereas ligation for 1 min resulted in an increase of 42% of the FFA. The acyl groups of poly-PI and PI in the control gerbil brain are enriched in 18:0 and 20:4, but those of DG, FFA, and PA have a higher proportion of 16:0 besides 18:0 and 20:4. However, a preferential increase in the proportion of 18:0 and 20:4 was shown for the DG and FFA in both types of ischemic treatments. It is concluded from the results that both models of ischemic treatment elicit a similar decrease in poly-PI and increase in DG, but differ in the amount of FFA release. The higher level of FFA release in the decapitative model suggests that other biochemical mechanisms may be activated to cause the additional release.


Psychosexual distress in women with gynecologic cancer: a feasibility study of an online support group.
The psychosexual concerns of gynecologic cancer patients are often unaddressed and there are limited resources available for women to deal with this highly sensitive topic. This feasibility study examines the participation rates and preliminary outcomes for an online support group designed specifically for women who are sexually distressed subsequent to gynecologic cancer treatment A 12-week online intervention was developed to address the psychosexual impact of gynecologic cancer. This intervention included a professionally moderated, asynchronous discussion forum as well as the provision of psycho-educational materials addressing the psychosexual impact of gynecologic cancer. Each week, a new topic was introduced and relevant material was posted on the website. Women were encouraged to share their experiences related to the topic. Twenty-seven, sexually distressed, remitted gynecologic cancer patients were randomly assigned to immediate treatment or a waitlist control condition. Participants completed questionnaires at baseline, 4-month and 8-month follow-ups assessing sexual distress as the primary outcome as well as anxiety, depression, and illness intrusiveness. Participation rates differed between the two groups, with greater participation occurring in the second group. Exit interviews indicated that the majority of the participants were satisfied with the intervention. Intent-to-treat analyses suggest a small effect for reduction in sexual distress This feasibility study suggests that women find this intervention acceptable. Further research is required to determine efficacy.


Urinary phthalate metabolite concentrations in relation to levels of circulating matrix metalloproteinases in pregnant women.
Phthalate exposure has been shown to be associated with adverse pregnancy outcomes. However, human studies informing relevant mechanistic pathways are lacking. Experimental studies have reported that matrix metalloproteinases (MMPs), which are responsible for extracellular protein degradation, may be upregulated in response to phthalate exposure. In this exploratory study we measured urinary phthalate metabolite concentrations, plasma MMP levels, and relevant covariates among 134 pregnant women. There were statistically significant or suggestive positive relationships between several phthalates, particularly between metabolites of di-(2-ethylhexyl) phthalate, with MMP-1 and MMP-9 levels. Further research is needed to confirm these results and how they may inform the mechanisms involved between phthalate exposure and adverse pregnancy outcomes.


The Risk of Acute and Chronic Pancreatitis in Celiac Disease.
Celiac disease (CD) is a chronic immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. A few studies reported a higher incidence of pancreatitis in the CD population. Using a large US database, we sought to describe the epidemiology, risk, and outcomes of acute pancreatitis (AP) and chronic pancreatitis (CP) in CD patients. We queried a multiple health system data analytics and research platform (Explorys Inc, Cleveland, OH, USA). A cohort of patients with a diagnosis of CD was identified. Subsequently, individuals who developed a new diagnosis of AP and CP after at least 30 days of being diagnosed with CD were identified. A multivariate regression model was performed to adjust for multiple confounding factors. Of the 72,965,940 individuals in the database, 133,400 (0.18%), 362,050 (0.50%), and 95,190 (0.13%) had CD, AP, and CP, respectively. New diagnosis of AP and CP after at least 30 days of CD diagnosis was 1.06%, 0.52%, respectively, compared to non-CD patients with 0.49% for AP and 0.13% for CP, P < .0001. In multivariate regression analysis, patients with CD were at higher risk of developing AP [OR 2.66; 95% CI 2.55-2.77] and CP [OR 2.18; 95% CI 2.04-2.34]. Idiopathic AP was the most common etiology among CD patients [OR 1.54; 95% CI 1.34-1.77]. In this largest US population database and after adjusting for several confounders, patients with CD were at increased risk of developing AP and CP. Celiac disease patients had worse outcomes and higher medical burden compared to non-CD patients. Recurrent abdominal pain that suggests pancreatic etiology, idiopathic pancreatitis, or elevation of pancreatic enzymes should warrant investigation for CD as a potential cause of pancreatic disease.


6,7-Dinitroquinoxaline-2,3-dione but not MK-801 exerts a protective effect against kainic acid neurotoxicity in the goldfish retina.
Recent findings indicated that the excitotoxicity of glutamate analogues was prevented in the mammalian nervous system by N-methyl-D-aspartate (NMDA) antagonists. The neurodegenerative effects of kainic acid, and the putative protection of MK-801 and 6,7-dinitroquinoxaline-2,3-dione (DNQX), were investigated by morphological studies showing the toxicity of kainic acid to the neurons of the inner nuclear layer, and measuring choline acetyltransferase and glutamate decarboxylase activities in the retina. In addition, the proliferation of Müller retinal cells was assumed as an index of neuronal degeneration and was quantified by counting glial fibrillary acidic protein immunopositive cells. Our observations suggest that the non-NMDA receptor antagonist DNQX exerted a protective effect on goldfish retinal neurons, while MK-801 did not prevent the neurotoxicity induced by kainic acid in the goldfish retina. This finding is in agreement with previous work on kainic acid toxicity in the goldfish optic tectum.


Pathogen distribution and drug resistance of nephrology patients with urinary tract infections.
Pathogen distribution characteristics of nephrology patients with urinary tract infections are studied, and drug resistance of nephrology and urinary tract infection disease are analyzed, so as to provide sufficient evidence for treatment of patients. Conduct randomized control study of 3500 cases of nephrology patients with urinary tract infections treated in different hospitals from December 2013 to December 2015, isolate pathogens in patients' urine samples, perform identification and drug sensitive test and then conduct detailed analysis of drug resistance of pathogens. Through isolation of pathogens, it can be found that all pathogens include Escherichia coli, Gram-positive cocci, gram-negative bacteria, fungi, Acinetobacter baumannii, Enterococcus faecalis, and urinary Enterococcus. Among them, proportion of E. coli is the largest. Patients have relatively high drug resistance to ceftriaxone, gentamicin, ciprofloxacin and cotrimoxazole. For nephrology patients with urinary tract infection, the main pathogen is E. coli, which has had some drug resistance. Drug resistance detection of pathogen should be strengthened in clinics, so as to provide strong guidance for clinical treatment and promote effective treatment of patients.


One-Step Self-Assembly of Multifunctional DNA Nanohydrogels: An Enhanced and Harmless Strategy for Guiding Combined Antitumor Therapy.
DNA nanostructure-based drug delivery system (DDS) has become an advanced therapeutic strategy for cancer because of its unsurpassed editability, intrinsic biodegradability, and tunable multifunctionality. An intelligent DNA nanosystem integrating targeting, immunostimulation, and chemotherapy was constructed based on unmethylated cytosine-phosphate-guanine oligonucleotides (CpG ODNs) DNA nanohydrogels (CpG-MUC1-hydrogel). By facile one-step self-assembly, the cross-shaped DNAs (C-DNAs) assembled from pH-responsive I-motif sequences and targeted MUC1 aptamer-immunoadjuvant CpG-fused sequences (CpG-MUC1) were integrated into DNA nanohydrogels with controllable size by the hybridization of DNA linkers. Subsequently, DOX was successively intercalated into the base pairs of CpG-MUC1-hydrogel, resulting in CpG-MUC1-hydrogel/Dox that would disassemble and release DOX and CpGs at acidic conditions. After MUC1-mediated internalization, CpG-MUC1-hydrogel/Dox dissociated in the endo/lysosomes and induced favorable apoptosis of tumor cells. Afterward, liberated CpGs triggered vast cytokine secretion from immune cells which elicited potent immune response against malignancy. Notably, CpG-MUC1-hydrogel induced an apoptosis effect on MCF-7 cells via significantly increasing the Bax/Bcl2 ratios and a higher level of tumor necrosis factor (TNF-α) on RAW264.7 cells than naked CpGs. Our results demonstrated that self-assembled CpG-MUC1-hydrogel represented an attractive DDS for precise delivery, potent immunostimulating activity, and considerable combination efficiency with few adverse effects, which is expected to make breakthroughs in clinical translation.


Tricorn-like proteases in bacteria.
The tricorn protease is an archaeal protease that forms massive proteasome-like capsids with a hollow chamber. beta-Propeller and PDZ domains are thought to play a role in substrate selection. By analysis of predicted proteins from novel bacterial genome sequences, we have identified four new bacterial tricorn-like proteases, complete with similar beta-propeller, PDZ and catalytic domains. We propose various hypotheses as to the function of these domains that can now be tested in the laboratory.


Elevated Aortic Stiffness after Pediatric Heart Transplantation.
In adults, arterial stiffness has been linked to the development of target end-organ damage, thought to be related to abnormal transmission of pulse pressure. Increased arterial stiffness and endothelial dysfunction have been hypothesized to contribute to the development of microvascular dysfunction and coronary allograft vasculopathy (CAV), an important comorbidity after heart transplantation. However, little data exists regarding arterial stiffness in pediatric heart transplantation and its influence on development of coronary allograft vasculopathy is not well understood. We sought to assess aortic stiffness and distensibility in pediatric post-heart transplant patients. A prospective, observational study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in patients aged < 21 years was conducted. Descending and ascending aorta M-modes were obtained from the subcostal long axis view, and the parasternal long axis view 3-5mm above the sinotubular junction, respectively. Two independent reviewers averaged measurements over 2-3 cardiac cycles, and Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) were calculated using previously validated methods. We recruited 39 heart transplant (HT) patients and 47 healthy controls. Median end diastolic dimension of the ascending aorta (donor tissue) was significantly larger in the transplant group than the control group (1.92 cm vs. 1.74 cm, p = 0.01). Ascending aortic distensibility in post-transplant patients was significantly lower than in the control group (4.87 vs. 10.53, p < 0.001). Ascending aortic stiffness index was higher in the transplant patients compared to the controls (4.63 vs. 2.21, p < 0.001). There is evidence of altered ascending aortic distensibility and stiffness parameters in post-heart transplant patients. Further studies are required to assess its influence on complications like development of coronary artery vasculopathy.


Purification of phosphatidylethanolamine N-methyltransferase from rat liver.
Phosphatidylethanolamine (PE) N-methyltransferase catalyzes the synthesis of phosphatidylcholine by the stepwise transfer of methyl groups from S-adenosylmethionine to the amino head group of PE. PE N-methyltransferase was solubilized from a microsomal membrane fraction of rat liver using the nonionic detergent Triton X-100 and purified to apparent homogeneity. Specific activities of PE N-methyltransferase with PE, phosphatidyl-N-monomethylethanolamine (PMME), and phosphatidyl-N,N-dimethylethanolamine (PDME) as substrates were 0.63, 8.59, and 3.75 mumol/min/mg protein, respectively. The purified enzyme was composed of a single subunit with a molecular mass of 18.3 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Methylation activities dependent on the presence of PE, PMME, and PDME and the 18.3-kDa protein co-eluted when purified PE N-methyltransferase was subjected to gel filtration on Sephacryl S-300 in the presence of 0.1% Triton X-100. All three methylation activities eluted with a Stokes radius 2.1 A greater than that determined for pure Triton micelles (molecular mass difference of 27.4 kDa). Two-dimensional analysis of PE N-methyltransferase employing nonequilibrium pH gradient gel electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the enzyme is composed of a single isoform. Analysis of enzyme activity using PE, PMME, and PDME at various Triton X-100 concentrations indicated the enzyme follows the "surface dilution" model proposed for other enzymes that act at the surface of mixed micelle substrates. Initial velocity data for all three lipid substrates (at fixed concentrations of Triton X-100) were highly cooperative in nature. Hill numbers for PMME and PDME ranged from 3 at 0.5 mM Triton to 6 at 2.0 mM Triton. All three methylation activities had a pH optimum of 10. These results provide evidence that a single membrane-bound enzyme catalyzes all three methylation steps for the conversion of PE to phosphatidylcholine.


Quantifying sources of environmental contamination with Toxocara spp. eggs.
A rich body of work has reported levels of infection with Toxocara species in definitive hosts, and the frequency of eggs in the environment, in many different regions and situations. These have greatly increased our understanding of the relationship between egg excretion from companion and wild animals and the risk of human infection by inadvertent ingestion of eggs from soil and other environmental reservoirs. Nevertheless, it is difficult to compare studies directly because of vagaries in sampling and laboratory methods, a preponderance of prevalence rather than abundance data, and a lack of studies that systematically sample different sympatric definitive host populations. Such comparisons could be instructive, for example to determine the relative contributions of different definitive host populations and categories to environmental contamination in specified areas, and hence guide priorities for control. In this article we use estimates of host density and infection levels in the city of Bristol, UK, as a case study to evaluate the relative contribution of sympatric cats, dogs and foxes to overall environmental contamination with eggs. Results suggest that dogs, especially those less than 12 weeks of age, dominate total egg output, but that this is modified by degree of access to public areas and removal of faeces, such that foxes could take over as the primary source of eggs. Results and conclusions are likely to differ among specific locations. The general aim is to show how an improved quantitative framework for epidemiological studies of Toxocara spp. egg contamination can help to advance understanding and the effectiveness of control strategies in future.


Evaluation of the Predictive Value of Urine Leukocyte Esterase Test in Chlamydia trachomatis and Neisseria gonorrhoeae Infection Among Males Attending HIV/STI Clinics in Guangdong Province, China.
Leukocyte esterase test (LET) detection is a simple and inexpensive test performed by urinalysis. This study investigated the predictive value of LET for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection among men attending HIV and sexually transmitted infection (HIV/STI) clinics in Guangdong Province, China. A total of 5,509 urine samples were collected from HIV and sexually transmitted infection clinics in Guangdong Province between 2017 and 2019. Specimens from 5,464 males were tested by both LET and nucleic acid amplification test (NAAT). Of 5,464 males, 497 (9.1%) tested positive for CT or NG by NAAT, with respective prevalence rates of 6.4% (95% confidence interval [95% CI]: 5.8-7.1%) and 3.8% (95% CI: 3.3-4.3%), including 1.2% (95% CI: 0.9-1.4%) co-infected. Compared to the HIV-negative individuals, individuals living with HIV tend to have a higher prevalence of CT, NG and co-infection with CT and NG. The LET sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CT were 46.4% (95% CI: 41.2-51.7%), 92.0% (95% CI: 91.2-92.7%), 28.4% (95% CI: 24.8-32.1%), and 96.1% (95% CI: 95.6-96.7%), respectively. The LET sensitivity, specificity, PPV, and NPV for NG were 68.4% (95% CI: 62.1-74.7%), 91.8% (95% CI: 91.1-92.6%), 25.0% (95% CI: 21.4-28.5%), and 98.7% (95% CI: 98.3-99%), respectively. Compared to the HIV-negative individuals, higher sensitivity and specificity were observed for HIV-positive individuals, but there was no statistical difference. The incremental cost-effectiveness ratio (ICER) using economic costs per additional person CT positive and NG positive was -$238.74 and -$145.60 compared with LET positive, respectively. LET is a cost-effective test and will be valuable for predicting CT and NG infection, which is highly prevalent in low- and middle-income countries.


NiTiNol hernia device stability in inguinal hernioplasty without fixation.
To determine whether the NiTiNol frame of a novel hernia repair device utilizing polypropylene mesh for inguinal hernioplasty remains stable and intransient without fixation after a minimum of 6 months. Twenty patients had 27 inguinal hernias repaired using a novel hernia repair device that has a NiTiNol frame without any fixation. Initial single-view, postoperative X-rays were compared with a second X-ray obtained at least 6 months later. The NiTiNol frame, which can be easily visualized on a plain X-ray, was measured in 2 dimensions, as were anatomic landmarks. The measurements obtained and the appearances of the 2 X-rays were compared to determine the percentage of change in device size and device stability with regard to device location and shape. There were minimal changes noted between the 2 sets of measurements obtained with an overall trend towards a slight increase in the size of the hernia repair device. The devices demonstrated intransience of position and stability of shape. The NiTiNol frame of a novel hernia repair device utilizing polypropylene mesh exhibits radiographic evidence of size and shape stability and intransience of position without fixation when used in inguinal hernioplasty after a minimum follow-up of 6 months.


Psychoendocrine correlates of sociosexual responsivity in older premenopausal primates.
Cycling older premenopausal female bonnet macaques (17 to 18 years) show decreased attractivity (mounting indices) and responsivity to males in short-term pair-testing compared to younger, fully mature cycling females (9 to 13 years). Comparison of age-group mean circulating levels of estrogen, progesterone, and testosterone during four phases of the menstrual cycle shows a significant decrement in older females only in the height of the estrogen surge during the periovulatory (estrous) phase of the cycle. Supplementation of older females with an estradiol + testosterone preparation (Deladumone, Squibb) did not restore behavioral sexual interaction to the level of younger females. The data suggest a gradual decline in sexual responsivity or arousal in older females which precedes the major endocrine changes of menopause. Such a lowering of responsivity appears comparable to that observed in aging (albeit sexually functional) human males.


Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.
Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC). We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot. Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line. Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.


A comparison of provider perspectives on cultural competency training: A mixed methods study.
We aimed to identify differences in training among colorectal cancer physicians and advanced practice providers with high and low cultural competency METHODS: Using explanatory sequential mixed methods, we surveyed providers and dichotomized into high and low cultural competency (CC) groups, conducted qualitative interviews, and analyzed verbatim transcripts using deductive and inductive codes to compared findings across groups using a joint display. Fifty-four of 92 providers (59%) responded; 10 respondents from each group (20/36 invited) completed semi-structured interviews about previous CC trainings. Low CC providers' training included explanations of cultural differences that, in practice, improved awareness and utilization of communication tools, but they also desired decision-making tools and cultural exposure. High CC providers' training included action-oriented toolkits. In practice, they admitted failures, improved communication, and attributed patient behaviors to external factors. High CC providers desired performance evaluations. Behaviorally-oriented CC training offered a robust foundation for culturally competent care.


Accuracy of AJCC staging for breast cancer patients undergoing re-excision for positive margins. American Joint Committee on Cancer.
The current AJCC protocol for breast cancer staging does not include additional tumor found at the time of re-excision in the calculation of tumor size. We hypothesize that the AJCC protocol may result in understaging and undertreatment of breast cancer patients who have additional tumor found at re-excision. In a retrospective chart review of breast cancer patients, patients with tumor present at re-excision for positive margins were placed in group 1 (n=72); patients with no tumor present at re-excision, or who underwent a single, negative margin procedure were placed in group 2 (n=147). Patients in group 1 had a higher risk of nodal metastases when compared to patients in group 2. Mean tumor size did not differ significantly between the subgroups. Positive re-excision was strongly associated with lymph node metastases on multivariate analysis after correction for age, grade, stage, and lymphatic invasion (odds ratio=3.13, 95% CI=1.58 6.18, P=.0011). Current AJCC guidelines may result in undertreatment of breast cancer patients with positive re-excisions. The presence of additional tumor at the time of re-excision should be considered when determining the need for systemic therapy, and may be relevant in determining T stage.


Molecular association of adsorbed water with lignocellulosic materials examined by micro-FTIR spectroscopy.
For lignocellulosic materials, water adsorption is extremely important for its product performance. For gaining a deeper understanding of moisture adsorption mechanisms, the molecular interactions between adsorbed water and a typical lignocellulosic material (i.e., wood) were studied using in-situ microscopic Fourier transform infrared (micro-FTIR) spectroscopy and a specially designed sample cell. The spectral shifts of 1733 cm(-1), 1604 cm(-1) and 1236 cm(-1) and different spectra between the moist and dry spectra indicated that carbonyl CO and CO groups preferred to combine with water molecules to form hydrogen bonds. From component band analysis of the spectral range of 2900-3700 cm(-1), three peaks at 3178 cm(-1), 3514 cm(-1) and 3602 cm(-1) were identified and assigned to strongly, moderately and weakly hydrogen-bonded water molecules, respectively. According to the variation trend of these hydrogen-bonded water molecules, three sections were divided for the adsorption process. Furthermore, the molecular structure of water absorbed by hydrophilic groups of wood in each section was demonstrated.


Serial measurements of facial asymmetry using a wooden tongue depressor in patients with congenital microtia.
Congenital microtia may be associated with hemifacial microsomia, but little is known about their correlation and development with aging. Historically, facial asymmetry is easily assessed by observing the occlusal cant using a tongue depressor. We serially measured the occlusal cant in children with microtia to evaluate change in facial asymmetry with growth. Since 2011, frontal photographs of patients with congenital microtia biting a tongue depressor were obtained and reviewed. The occlusal angle was compared between the baseline and final photographs, and the change was compared between cant-positive (>3° at baseline) and cant-negative (<3° at baseline) groups. Multivariate analysis was conducted to determine variables associated with the change in occlusal angle. Overall, 105 patients were enrolled. With a mean age of 5.4 years at baseline and a mean follow-up of 3.9 years, clinically significant aggravation was observed in 15.4% and 24.2% of cant-positive and cant-negative patients, respectively. Hemifacial microsomia (OR, 4.825; p = 0.005) and occlusal angle at baseline (OR, 0.821; p = 0.045) were associated with aggravation, but the severity of microtia showed no significant association. When hemifacial microsomia was present, the occlusal cant seemed to be aggravated in children with microtia at later ages. When the occlusal cant was present without noticeable hemifacial microsomia, some compensation in facial asymmetry was expected. The use of a wooden tongue depressor is a simple, non-invasive, and radiologic hazard-free aid to detect notable change in facial asymmetry in children with microtia.


[Radiation disturbance of RNA metabolism during interphase death of lymphoid cells].
The data are reviewed concerning the radiation--induced disturbances of RNA metabolism in lymphoid cells. The role of the observed disorders in activation and realization of the interphase cell death program is discussed.


Countering the declining use of lithium therapy: a call to arms.
For over half a century, it has been widely known that lithium is the most efficacious treatment for bipolar disorder. Yet, despite this, its prescription has consistently declined over this same period of time. A number of reasons for this apparent disparity between evidence and clinical practice have been proposed, including a lack of confidence amongst clinicians possibly because of an absence of training and lack of familiarity with the molecule. Simultaneously, competition has grown within the pharmacological armamentarium for bipolar disorder with newer treatments promoting an image of being safer and easier to prescribe primarily because of not necessitating plasma monitoring, which understandably is appealing to patients who then exercise their preferences accordingly. However, these somewhat incipient agents are yet to reach the standard lithium has attained in terms of its efficacy in providing prophylaxis against the seemingly inevitable recrudescence of acute episodes that punctuates the course of bipolar disorder. In addition, none of these mimics have the additional benefits of preventing suicide and perhaps providing neuroprotection. Thus, a change in strategy is urgently required, wherein myths regarding the supposed difficulties in prescribing lithium and the gravity of its side-effects are resolutely dispelled. It is this cause to which we have pledged our allegiance and it is to this end that we have penned this article.


Effects of spatial memory on morphine CPP and locomotor sensitization in mice.
Drug addiction is associated with memory processes. We simultaneously measured conditioned place preference (CPP) and locomotor sensitization to investigate the influence of spatial memory retrieval on morphine reward and psychomotor excitement. According to their performance in space probe trial involving the Morris water maze mice were assigned to high (including morphine and saline subgroups, H-Mor and H-Sal) and low spatial memory retrieval ability groups (L-Mor and L-Sal). Morphine (10mg/kg) produced significant CPP in L-Mor and H-Mor mice, although, L-Mor mice showed a significantly greater response to morphine. During the development period of behavior sensitization, no significant group-by-day interaction was found. However, locomotor activities of L-Mor mice were also significantly higher than H-Mor mice during the expression period of behavior sensitization. Our findings suggested that the spatial memory retrieval ability of mice influences morphine CPP, as well as behavioral sensitization. Thus, spatial memory might be implicated in drug addiction.


Urinary nitrite excretion and urinary variables in patients with primary nocturnal frequency of micturition: effects of indomethacin suppositories.
Urinary nitrite excretion was measured in patients with primary nocturnal frequency of micturition (PNFM) and in normal individuals. Effects of indomethacin suppository on urine volume and other urinary variables were evaluated. The study comprised seven patients with PNFM and seven healthy control (age range 30-45 years). Nitrite was assayed in spot morning urine samples; urine volume, urine osmolality and electrolytes, serum osmolality and electrolytes and functional bladder capacity (FBC) were assayed. Both groups were then given 100 mg of indomethacin suppository daily for a maximum of 10 days and urinary variables were re-evaluated during day 10. Results showed that urinary nitrite excretion of patients with PNFM was greater than that of the normal subjects (230+/-62 umol/l vs. 42+/-30 umol/l, P<0.05). The mean (SD) 24 h urine volume and osmolality, the night urine volume and osmolality, serum osmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), and urinary excretion of glucose and potassium were lower in patients with PNFM as compared with normal individuals, although not statistically significantly so, except for FBC that was significantly lower in the patients. Urinary excretion of sodium, calcium, chloride, phosphorus, magnesium, day-night urinary volume ratio, spot morning osmolality, nocturnal index, and nocturnal polyuria index were higher in patients with PNFM. Indomethacin decreased the 24 h urinary volume by 21%, creatinine clearance by 12%, osmolar clearance by 14% and urinary protein excretion by 38% in the patients. These variables decreased by 26, 45, 17 and 12% respectively in the healthy subjects, whereas 24 h urinary protein excretion increased mildly by 9%. Indomethacin increased day-night urinary volume ratio by 73% in the healthy subjects. It might be concluded that urinary nitrite excretion, urinary excretion of sodium, chloride, phosphorus, calcium, and magnesium increased and FBC decreased in patients with PNFM; Indomethacin decreased urinary volume, FENa, FEK, osmolar clearance, and free water clearance in the healthy subjects and the patients. These might explain the mechanism of action of indomethacin to reduce frequency of voiding. The possible interaction of prostaglandin and NO in the pathogenesis of PNFM is discussed.


[Effect of nutritional status in childhood on health status in adulthood].
To investigate the effect of nutritional status in childhood on health status in adulthood. Data were collected from the China Health and Nutrition Survey in 1991, 1993, 1997, 2001, 2004 and 2006, and the subjects were older than 2 and no more than 18 year-old at the Survey in 1991 and remained in the same cohort with completed records through all six surveys. Mixed effect linear model was used to study the trajectory of BMI. Proportional hazards model was used to study the hazard risk of hypertension in adulthood. Generally, the thinness or overweight-obesity status in childhood followed a same trend till adulthood. Nutritional status in childhood and the educational level of their parents appeared to be related to risk factors of hypertension in adulthood. The hazard ratio of not developing hypertension for additional 1 gram of protein intake per day in male subjects was 0.991, and which for additional 1 kcal of energy intake per day in female subjects was 0.9997. The nutritional health status in childhood keeps the same trajectory till adulthood.


Induces vasodilatation of rat mesenteric artery in vitro mainly by inhibiting receptor-mediated Ca(2+)-influx and Ca(2+)-release.
The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1 microM, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the (alpha1-adrenoreceptor. The beta-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and CaCI2 in Ca(2+)-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular Ca2+ influx through the receptor-operated calcium channels and intracellular Ca2+ release from the Ca2+ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular Ca2+ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated Ca(2+)-influx and Ca(2+)-release, and partly from the endothelium mediated by EDHF.


Huntington's disease influences employment before and during clinical manifestation: A systematic review.
Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working. This systematic review focuses on summarizing which disease-specific characteristics influence employment and working capacity in HD. Twenty-three studies were identified and showed that while employment and working capacity in HD are negatively influenced by cognitive decline and motor impairments, apathy already plays a role in the prodromal stage. Moreover, the influence of HD transcends the clinical manifestation of the disease, as some people at risk are already experiencing the impact of HD on employment through fear of or actual genetic discrimination. Employment and working capacity are not influenced by predictive testing for HD in and of itself.


Temperature-dependent flagellar motility of demembranated, cytosol-free fowl spermatozoa.
A rapid and gentle procedure for preparing demembranated, cytosol-free sperm models was applied to fowl spermatozoa. Intact spermatozoa were introduced to a Triton X-100-containing extraction medium layered on top of a discontinuous Percoll gradient in a 1.5 ml microfuge tube. After brief exposure to the extraction medium, spermatozoa were separated from the plasma membrane and detergent-soluble components by centrifugation through a 55% Percoll layer, finally collecting on top of a 90% Percoll cushion from where they were recovered. Optimum conditions consisted of a Triton X-100 concentration in the extraction medium of 0.15%, duration of demembranation time of 1.5 min and ATP concentration in the reactivation medium of 0.5 mM. Demembranated sperm models obtained by this procedure could be reactivated, and the motility at 30 degrees C was more than 60%, but negligible at 40 degrees C. These values were similar to those obtained from the conventional method, in which centrifugation is not carried out, and which results in some of the cytosolic components being transferred to the reactivation medium along with the spermatozoa. Inhibition of motility was observed following the addition of EGTA or myosin light chain kinase (MLCK) substrate peptide at 30 degrees C, whilst the presence of protein phosphatase inhibitors, such as calyculin A or okadaic acid, permitted the restoration of motility at 40 degrees C. These results demonstrate that the axoneme and/or accessory cytoskeletal components are directly involved in the temperature-dependent regulatory system of fowl sperm motility in the absence of plasma membrane and/or soluble components of cytoplasm.


Bis[2,3-bis-(pyridin-2-yl)pyrazine-κ2 N 2,N 3]palladium(II) dinitrate aceto-nitrile monosolvate.
The title compound, [Pd(C14H10N4)2](NO3)2·CH3CN, consists of a cationic PdII complex, two anions and one lattice solvent mol-ecule, all in general positions. In the complex, the PdII cation is four-coordinated in a slightly distorted square-planar geometry defined by the four N atoms of two bidentate 2,3-di-2-pyridyl-pyrazine ligands. The complex, anions and solvent mol-ecule are linked by weak C-H⋯O inter-molecular hydrogen bonds. In the crystal, the complex mol-ecules are stacked in columns along the a axis.


Comparative study between peripherally and centrally acting sublethal and lethal doses of Leiurus quinquestriatus scorpion venom in rabbits: The usefulness of the sodium channel blocker lidocaine.
Scorpion envenomation is common among desert dwellers, affecting several systems and resulting in multiple organ dysfunction (MOD) or failure (MOF), mainly due to their action on Na(+) channels. Although scorpion venoms toxins do not pass the blood brain barrier, their CNS effects are prominent, occurring in conjunction with, or as an aftermath of peripheral actions of the venom. To determine the ability of venom of the common scorpion Leiurus quinquestriatus (LQQ) to induce MOD or MOF when injected into rabbits in micro quantities centrally (intracerebroventricularly, i.c.v.) or macro amounts peripherally (s.c. or i.v.). Also, to assess if the Na(+) channel blocker lidocaine can protect rabbits from the resultant manifestations. Rabbits were injected with LQQ venom centrally or peripherally, in either sublethal or lethal doses, and MOD or MOF determined by assessing: cardiac output (CO), estimated hepatic blood flow (EHBF), biochemical parameters indicative of cardiac/hepatic/renal and pancreatic functions, blood pressure (BP), survival, lung/body index (LBI, indicative of pulmonary edema), and/or histological changes in hearts, lungs, livers plus kidneys. In pre-treatment experiments, lidocaine was injected 40 min before venom and protective ability examined. LQQ venom in sublethal doses caused comparable significant reductions (vs control) in CO and EHBF when injected i.c.v. (2 μg kg(-1)) or s.c. (0.2 mg kg(-1)). Both routes caused gradual dose-related enhanced levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine, glucose and amylase, indicating MOD. Also, characteristic venom-induced changes in BP were evident after lethal doses of venom i.v. (0.5 mg kg(-1)) or i.c.v. (3 μg kg(-1)). Histological changes in the organs plus LBI were comparable after i.c.v. and i.v. venom injection, with animals ultimately exhibiting MOF. Lidocaine (1 mg kg(-1) i.v., then infusion 50 μg kg(-1) min(-1), 30 min before venom), protected the animals from MOF evoked by lethal doses of the venom (whether injected centrally or peripherally), as evidenced by the amelioration of the venom's effects on blood pressure, LBI, survival and multiple organ histopathological manifestations. LQQ venom, whether injected centrally or peripherally caused comparable systemic dose-dependent MOD or MOF, with the latter attenuated by the Na(+) channel blocker lidocaine, indicating a role for Na(+) channels.


Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.
Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. ClinicalTrials.gov, NCT01026818.


Complete genome sequence of a novel closterovirus isolated from Dregea volubilis.
The complete genome sequence of a putative novel closterovirus, tentatively named "Dregea volubilis closterovirus 1" (DvCV1, GenBank accession no. MZ779122), infecting Dregea volubilis in China was determined using high-throughput sequencing (HTS). The complete genome sequence of DvCV1 consists of 16,165 nucleotides (nt) and contains nine ORFs. The genome structure of DvCV1 is typical of members of the genus Closterovirus. Complete genome sequence analysis showed that DvCV1 shares 41.4-48.4% nucleotide sequence identity with other known closteroviruses. The putative RNA-dependent RNA polymerase (RdRp), heat shock protein 70-like protein (HSP70h), and coat protein (CP) of DvCV1 share 46.80-62.65%, 31.06-51.80%, and 28.34-37.37% amino acid sequence identity, respectively, with the RdRp, HSP70h and CP of other closteroviruses. Phylogenetic analysis based on HSP70h aa sequences placed DvCV1 alongside other members of the genus Closterovirus in the family Closteroviridae. These results suggest that DvCV1 is a new member of the genus Closterovirus. This is the first report of a closterovirus infecting D. volubilis.


Genetic parameter estimates for milkability traits and their relationship with somatic cell score in South African Holstein cattle.
Milkability is an important functional trait, which is directly related to milking costs and udder health. There are no milkability traits incorporated in the South African dairy cattle breeding objectives and genetic parameter estimates for these traits are not available in this population. The main objective of the study was, therefore, to estimate the genetic parameters for milkability traits and its correlation with somatic cell scores in South African Holstein cattle. Data consisted of production and milkability records of 2719 Holstein cows, from ten herds, collected from 2016 to 2018. Genetic parameters were estimated by a multi-trait animal model using the restricted maximum likelihood (REML) procedure. Means for milking time (MT), average milk flow (AMF), maximum milk flow (MMF), and somatic cell score (SCS) were 5.20 min, 1.91 kg/min, 2.99 kg/min, and 2.06, respectively. The heritability estimates were low to moderate from 0.19 ± 0.07, 0.24 ± 0.06, 0.36 ± 0.11, and 0.41 ± 0.12, respectively, for SCS, AMF, MT, and MMF. The genetic correlations were significant (P < 0.05) among the three milkability traits ranged from - 0.31 ± 0.05 between AMF and MT to 0.85 ± 0.02 between AMF and MMF. Positive genetic correlations were observed between AMF and MMF, while the correlations for MT with the remaining milkability traits were negative. Genetic correlations of SCS with AMF, MMF, and MT were - 0.13 ± 0.04, 0.13 ± 0.04, and - 0.25 ± 0.12, respectively. The mean estimated breeding value (EBV) was estimated using cattle birth dates, and there was an increase in AMF of 0.0001 kg/min EBV per year on cattle born during the period 2002 to 2014. Maximum milk flow also showed an increasing genetic trend of 0.0003 kg/min per year over the same period. On the other hand, the genetic trend for MT was undesirable, as it increased by 0.0003 kg/min per year. The moderate to high heritability estimates for milkability traits showed that selection for improvement was possible in South African Holstein cattle. High genetic correlation between AMF and MMF implied that these two may be regarded as the same trait. Milking time can contribute towards improving the accuracy of estimating EBVs for SCS in a multi-trait analysis, and vice versa, due to the moderate correlation between the two traits. The marginal genetic trend in milkability traits may be an interrelated response to selection of other traits already under selection in the population such as SCS. Results of the current study provided a basis for including milkability traits of South African Holstein cattle in the breeding objectives.


Sweet complementarity: the functional pairing of glycans with lectins.
Carbohydrates establish the third alphabet of life. As part of cellular glycoconjugates, the glycans generate a multitude of signals in a minimum of space. The presence of distinct glycotopes and the glycome diversity are mapped by sugar receptors (antibodies and lectins). Endogenous (tissue) lectins can read the sugar-encoded information and translate it into functional aspects of cell sociology. Illustrated by instructive examples, each glycan has its own ligand properties. Lectins with different folds can converge to target the same epitope, while intrafamily diversification enables functional cooperation and antagonism. The emerging evidence for the concept of a network calls for a detailed fingerprinting. Due to the high degree of plasticity and dynamics of the display of genes for lectins the validity of extrapolations between different organisms of the phylogenetic tree yet is inevitably limited.


[The Herbert system of screw osteosynthesis in fracture of the scaphoid bone].
Indications and different techniques in operating on fractures of the scaphoid are summarised. The "Herbert Scaphoid Bone Screw System" is described. Instrumentation, operative technique and typical clinical applications are shown. The advantages and disadvantages are discussed.


Revealing the ventral amygdalofugal pathway of the human limbic system using high spatial resolution diffusion tensor tractography.
The amygdala is known to have a role in core processes regulated by the limbic system such as motivation, memory, emotion, social behavior, self-awareness as well as certain primitive instincts. Several functional studies have investigated some of these brain tasks of the human limbic system. However, the underlying neuronal fiber connectivity of the amygdalo-diencephalon, as part of the limbic system, has not been delineated separately by prior diffusion-weighted imaging studies. The ability to trace the underlying fiber connections individually will be helpful in understanding the neurophysiology of these tracts in different functions. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine connections of the amygdala, hypothalamus, septum or other adjacent limbic structures have yet to be elucidated by diffusion-weighted tractography studies. We therefore aimed to further investigate these fine neuronal connections using fiber tractography and high spatial resolution diffusion tensor imaging on 3T on 15 healthy right-handed male human subjects (age range 24-37 years). The ventral amygdalofugal pathway, anterior commissure and stria terminalis are the three main efferent pathways of the amygdala. We delineated the detailed trajectories of the ventral amygdalofugal tract, anterior commissure and their connections bilaterally in 15 normal adult human brains. Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to demonstrate the trajectory of amygdalofugal tract and its connections to the hypothalamic and septal nuclei. We further revealed, for the first time, the close relationship of the amygdalofugal tract and anterior commissure with the fornix, stria terminalis and uncinate fasciculus bilaterally in 15 healthy adult human brains.


A macroevolutionary pathway to megaherbivory.
Several scenarios have been proposed to explain rapid net size increases in some early Cenozoic mammalian lineages: sustained and gradual directional change, successive occupation of adaptive zones associated with progressively larger body sizes, and nondirectional evolution associated with branching events in combination with higher diversification potential of the larger lineages. We test these hypotheses in brontotheres, which are among the first radiations of mammals that consistently evolved multitonne sizes. Body-mass evolution in brontotheres mainly occurred during speciation and had no preferential direction. Long-term directional change stemmed from the higher survival of larger lineages in less-saturated herbivore guilds. Our study emphasizes the role of differential species proliferation in explaining the long-term phenotypic trends observed in the fossil record, which are more than an accumulation of steady microevolutionary changes.


Age-related changes in hormones in impotent men. Jefferson Sexual Function Center.
A total of 818 impotent men were evaluated in a multidisciplinary Sexual Function Center for reproductive hormone levels. Data are presented demonstrating an overall rate of endocrinopathy at 19.3 percent. Various age-dependent trends in the incidence of abnormal levels are noted. Hypogonadism as well as hyperpituitarism appear to increase in incidence with increasing age. Hyperprolactinemia, however, seems to be relatively constant in occurrence. Because of the likelihood of detecting endocrine abnormalities, a recommendation is made for routine hormonal screening of all patients complaining of impotence.


Hepatic metallothionein in a teleost (Prochilodus scrofa) exposed to copper at pH 4.5 and pH 8.0.
Copper accumulation and induction of metallothionein (MT) were investigated in the liver of juvenile Prochilodus scrofa exposed to copper (96 h-LC50) at pH 4.5 (LC50=98+/-0.8 microg Cu l(-1)) and pH 8.0 (LC50=16+/-0.5 microg Cu l(-1)) at 20 degrees C. No significant difference was found in copper accumulated in the liver at either pH. The ratio between copper accumulation in the liver after 96 h exposure and the copper in the water at pH 4.5 and 8.0 was 5.1 and 34.4, respectively. MT in the liver of fish exposed to copper was isolated by DEAE-Sepharose chromatography and identified by SDS-PAGE. No MT was identified in the controls. MT concentration was 126.8+/-21.5 and 167.4+/-25.6 microg g(-1) wet mass in fish exposed to copper at pH 4.5 and pH 8.0 (P>0.05), respectively. The results indicate that the pH of the water is a determining factor in copper toxicity, and the increased concentration of MT in the liver of P. scrofa exposed to copper suggests the possibility of using MT as a biomarker to evaluate the biological response of this species to copper contamination in aquatic environments.


Tumorigenic adenovirus type 12 E1A inhibits phosphorylation of NF-kappaB by PKAc, causing loss of DNA binding and transactivation.
Human adenovirus type 12 (Ad12) E1A protein (E1A-12) is the key determinant of viral tumorigenesis. E1A-12 mediates major histocompatibility complex class I (MHC-I) shutoff by inhibiting the DNA binding of the transcriptional activator NF-kappaB (p50/p65) to the class I enhancer. This enables Ad12 tumorigenic cells to avoid class I recognition and lysis by cytotoxic T lymphocytes. In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase A (PKAc) is essential for NF-kappaB DNA binding and transactivation activity. Treatment with H89 and knockdown of PKAc in cells led to the inhibition of phosphorylation at p50 Ser(337) and p65 Ser(276) and loss of DNA binding by NF-kappaB. Importantly, NF-kappaB phosphorylation by PKAc was repressed by tumorigenic E1A-12, but not by nontumorigenic Ad5 E1A (E1A-5). The stable introduction of E1A-12 into Ad5 nontumorigenic cells resulted in a decrease in the phosphorylation of NF-kappaB, loss of NF-kappaB DNA binding, and the failure of NF-kappaB to activate a target promoter, as well as diminution of MHC-I transcription and cell surface expression. Significantly, the amount and enzymatic activity of PKAc were not altered in Ad12 tumorigenic cells relative to its amount and activity in nontumorigenic Ad5 cells. These results demonstrate that E1A-12 specifically prevents NF-kappaB from being phosphorylated by PKAc.


Citrulline as a diagnostic parameter and a major amino acid constituent of cerebrospinal fluid in hepatic coma.
Free amino acids of cerebrospinal fluid and serum in hepatic coma have been studied. Citrulline was found to form about 80% of the total free amino acids in cerebrospinal fluid, whereas serum contained slightly higher levels of tyrosine, methionine, phenylalanine and glutamine. The higher level of citrulline in cerebrospinal fluid may be attributed to the inhibition of argininosuccinic acid synthetase in this disease.


What is normal? A field approach to characterizing health and management of the nation's animal populations.
There is a growing demand for information about the health and well-being of animals on farms. Such information has many uses. In some instances such information is used locally by livestock owners and producers to gauge their position relative to their peers. In other instances the information can be used at a national or international level by policy makers and trade negotiators. Animal health companies use such information to target research and product development. Academicians and other educators use information on animal health to teach future members of the agricultural industries. In addition, consumers are asking more questions about the manner in which animals are raised and cared for on farms. With so many stakeholders with an interest in such information there is a need for objective data collected with credible methods covering a substantial proportion of the population of interest. Such efforts are unlikely to be accomplished by entities other than a nationally focused unit in the government. The United States Department of Agriculture's National Animal Health Monitoring System (NAHMS) has been providing management and health-related data on the United States livestock and poultry populations for nearly 20 years.


Quantitating aortic regurgitation by cardiovascular magnetic resonance: significant variations due to slice location and breath holding.
Compare variability in flow measurements by phase contrast MRI, performed at different locations in the aorta and pulmonary artery (PA) using breath-held (BH) and free-breathing (FB) sequences. Fifty-seven patients with valvular heart disease, confirmed by echocardiography, were scanned using BH technique at 3 locations in the ascending aorta (SOV = sinus of Valsalva, STJ = sinotubular junction, ASC = ascending aorta at level of right pulmonary artery) and 2 locations in PA. Single FB measurement was obtained at STJ for aorta. Obtained metrics (SV = stroke volume, FV = forward volume, BV = backward volume, RF = regurgitant fraction) were evaluated separately for patients with aortic regurgitation (AR, n = 31) and mitral regurgitation (n = 26). No difference was noted between the two measurements in the PA. Significant differences were noted in measured SV at different aortic locations. SV measurements obtained at ASC correlated best with the measurements obtained in the PA. Strongest correlation of AR was measured at the STJ. Measurements of flow volumes by phase contrast MRI differ depending on slice location. When using stroke volumes to calculate pulmonary to systemic blood flow ratio (Qp/Qs), ASC should be used. For quantifying aortic regurgitation, measurement should be obtained at STJ. • Aortic regurgitation can be accurately measured by MRI. • Aortic regurgitation measurement by MRI varies according to the location where measured. • Aortic regurgitation can also be measured by MRI without breath hold.


The use of light-cured material for immediate hollow obturator prosthesis.
Surgical obturator prostheses for oronasal defects frequently require major alterations because of rapid changes in the defect following surgery. When necessary, the closing of the superior surface of the obturator can be completed as an office procedure by using light-cured acrylic resin. A step-by-step method for this procedure is described. The nonporous nature of the material used prevents accumulation of mucous and debris in the hollow extension.


Synergistic antimicrobial effect of nisin whey permeate and lactic acid on microbes isolated from fish.
The antimicrobial activity of a combination of lactic acid and whey permeate fermented by a nisin-producing Lactococcus lactis strain was tested by the agar diffusion method using bacteria isolated from fish as test organisms. Lactic acid inhibited all bacterial strains studied, but nisin whey permeate inhibited Gram-positive bacteria only. The combination was more effective than lactic acid alone against Pseudomonas fluorescens and Staphylococcus hominis isolated from fish, and Pseudomonas aeruginosa ATCC9721 and Micrococcus luteus ATCC9341.


Misdiagnosis of a nasopalatine duct cyst: a case report.
Nonendodontic lesions misdiagnosed as pathoses of endodontic origin are often referenced in the literature. One of the most frequent nonodontogenic cysts of the oral cavity, the nasopalatine duct cyst (NPDC), can be misdiagnosed as endodontic in nature. A case is presented in which a patent NPDC was originally diagnosed as a sinus tract with subsequent endodontic nonsurgical retreatment and eventual extraction before endodontic consultation. After surgical treatment, a histopathologic diagnosis of an NPDC was confirmed. If diagnosed incorrectly, inappropriate endodontic treatment of a NPDC may be initiated to include unnecessary extraction. An increased understanding of anatomy, the use of appropriate diagnostic tests to include cone-beam computed tomography imaging, and key examination techniques to distinguish endodontic lesions from nonendodontic pathoses are imperative for an accurate differential diagnosis and appropriate treatment outcome.


[App-based self-monitoring in type 2 diabetes].
The success of self-monitoring in the treatment of type 2 diabetes mellitus has already been verified in several studies. To date there are a multitude of smartphone apps which support diabetic patients in systematically recording and analyzing relevant health data; however, most of these smartphone apps are primarily developed for a young target group. As part of this study we examined to what extent a smartphone app for self-monitoring is used by older diabetic patients. In this study 36 adults with type 2 diabetes mellitus older than 60 years were included. After a comprehensive training course the participants used the application for 3 months. Reminders for medication, physical activity and diet could be set and recorded health data, such as weight or blood sugar, could be entered into the app. After 3 months the data were analyzed concerning usage behavior and impact on overall health. Data analysis revealed intensive usage of the smartphone app (90 % on a daily basis). Furthermore, according to the patients, after the study period significant improvements in medication adherence and psychological well-being were recorded [t[35] = -2.24, p < 0.05). Additional motivational elements did not influence the usage behavior by older adults. Until now only a small proportion of older adults used smartphone health apps, despite the ubiquitous availability. These apps have to be tailored to the requirements of older adults so that the market will be opened up to them. Using self-monitoring apps can help older adults to structure their daily routine despite their disease.


Degradation performance of methylene blue in metal nanoparticle modified 3D mesoporous wood microchannels.
Wood has a rich three-dimensional pore structure and many bottom-up nanochannels. However, the structure of wood itself has limited ability to adsorb dyes, so the effective combination of the unique structure of wood and Pd NPs was studied to achieve efficient degradation of dyes. First, the three-dimensional structure of natural wood is optimized by combining the complex pore structure of wood with Pd NPs to improve the contact process between the dye and Pd NPs. Then, Pd (II) ion can be well reduced to Pd NPs by wood lignin. In addition, Pd NPs can be fixed by hydroxyl groups on cellulose in wood. The flow state inside Pd NPs/wood film and the contact area between catalyst and dye were discussed in detail by hydrodynamic simulation, which filled the gap. It provides reference for composite structure. When Pd NPs/wood membrane was used to treat methylene blue (MB), the degradation efficiency was up to 96.7%, which was 90% higher than that of natural wood. Its TOF value was 1.82 molMB molPd-1min-1, which was higher than that in the previous literature. Therefore, the novelty of this study is that the mechanism of catalytic degradation of MB by Pd nanoparticles/wood composites is reported for the first time. The internal flow mode and contact condition of the new material are understood, which has a good application prospect.


Child maltreatment prevalence and mental disorders outcomes among American Indian women in primary care.
To examine (1) the prevalence, types, and severity of child abuse and neglect (CAN) and (2) the relationship between CAN and lifetime psychiatric disorders among American Indian women using primary care services. A cross-sectional study was conducted among 234 American Indian women, age 18-45 who presented for outpatient ambulatory services at a community-based Indian Health Service Hospital in Albuquerque, New Mexico. Dependent measures included mood, substance abuse, and anxiety disorders as well as posttraumatic stress disorder (PTSD) as measured by the Composite International Diagnostic Interview. CAN was assessed using the Childhood Trauma Questionnaire. Approximately three-quarters of respondents (76.5%; 95% CI = 70.4, 81.7) reported some type of childhood abuse or neglect; over 40% reported exposure to severe maltreatment. Severity of child maltreatment was associated in a dose response manner with lifetime diagnosis of mental disorders. After adjusting for social and demographic correlates, severe child maltreatment was strongly associated with lifetime PTSD (prevalence ratio [PR] 3.9; 95% CI = 1.9, 8.0); and was moderately associated with lifetime substance use disorders (PR = 2.3; 95% CI = 1.6, 3.3); mood disorders (PR = 2.1; 95% CI 1.4, 3.2); and with two or more disorders (PR = 2.3; 95% CI = 1.6, 3.4). CAN was common in our sample of American Indian women in primary care and was positively associated with lifetime psychiatric disorders outcomes. Screening for CAN and psychiatric disorders would enhance the treatment of patients seeking primary care services. Primary prevention of child maltreatment might reduce the high prevalence of mental disorders among American Indian women.


Significance of location (anterior versus inferior) and type (Q-wave versus non-Q-wave) of acute myocardial infarction in patients undergoing percutaneous transluminal coronary angioplasty for postinfarction ischemia.
Predictors of increased risk for recurrent cardiac events and death after acute myocardial infarction include postinfarction myocardial ischemia, anterior location of the infarct, and non-Q-wave versus Q-wave infarction. Although coronary angioplasty is performed in patients with postinfarction ischemia to alleviate symptoms, the outcome according to location and type of infarction and the effect on prevention of subsequent myocardial infarction and death are not known. To determine if location and type of myocardial infarction provide prognostic information in patients with postinfarction ischemia, we analyzed morbidity and mortality during and after coronary angioplasty according to the location (anterior vs inferior) and type (Q-wave vs non-Q-wave) of myocardial infarction in 505 consecutive patients. The incidence of recurrent angina, repeat coronary angioplasty, coronary bypass surgery, reinfarction, and death during long-term follow-up after hospital discharge (mean 34 +/- 19 months) for the 440 patients with an initial successful angioplasty was also compared. During the procedure, there was no difference in the primary success rate or mortality among the different groups; however, more patients with anterior non-Q-wave myocardial infarction underwent emergent bypass grafting after unsuccessful coronary angioplasty (p = 0.001). Multivariate Cox proportional-hazards analyses controlling for age, gender, number of diseased vessels, location, type of infarction, and year of coronary angioplasty revealed that more patients with anterior infarction had > or = 1 cardiac event (repeat angioplasty, coronary artery bypass grafting, reinfarction, or death) than did those with inferior infarction (RR 1.80, 95% confidence interval [Ci] 1.22 to 2.65, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of the presentation of remote visual stimuli on visual responses of cat area 17 and lateral suprasylvian area.
Single units were recorded extracellularly from area 17 and lateral suprasylvian area (LSSA) in curarized cats. Visual stimuli, usually a 10 degree black spot, were introduced abruptly in the visual field remote from the discharge area of a neuron's receptive field and moved at a speed of about 30 degrees/sec. The effect of these remote stimuli (S2) on the reponse to a restricted visual stimulus (S1) crossing the discharge area was studied. It was found that most units in area 17 were not affected by the presentation of remote stimuli, the remainder being either slightly facilitated or slightly inhibited. In contrast the LSSA neurons were usually inhibited by the presentation of S2: this effect was strong, was present in all classes of LSSA neurons and was independent of the relative directions of movement of S1 and S2. On the basis of these data and those previously obtained from the superior colliculus it is concluded that the way the extrageniculate centres respond to a stimulus abruptly introduced in the visual field is substantially different from that of the striate cortex. Only in the extrageniculate centres a new stimulus, besides exciting the neurons which correspond to the position of the stimulus in the field, concomitantly decreases the responses of neurons located in positions of the visual field remote from that stimulus. Possible behavioral implications of the findings are discussed.


Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus.
Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological control of S. aureus. Mass spectrometric analysis reveals that the glycation state of C3 is the same regardless of glucose concentration over a one-hour time period. However, in conditions of elevated glucose C3 appears to undergo structural changes.


Synthesis and pharmacological evaluation of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.
A series of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for their bradycardic activities in isolated guinea pig right atria and in urethane-anesthetized rats. These efforts resulted in identification of the compound 8a, which exhibits potent bradycardic activity with minimal influence on mean blood pressure in urethane-anesthetized rats. Oral administration of compound 8a to conscious rats revealed increased potency and prolonged duration of action when compared to Zatebradine.


Mental disorders and risk of accidental death.
Little is known about accidental death risks among psychiatric patients. To examine this issue in the most comprehensive study to date. National cohort study of all Swedish adults (n = 6 908 922) in 2001-2008. There were 22 419 (0.3%) accidental deaths in the total population, including 5933 (0.9%) accidental deaths v. 3731 (0.6%) suicides among psychiatric patients (n = 649 051). Of persons who died from accidents, 26.0% had any psychiatric diagnosis v. 9.4% in the general population. Accidental death risk was four- to sevenfold among personality disorders, six- to sevenfold among dementia, and two- to fourfold among schizophrenia, bipolar disorder, depression or anxiety disorders, and was not fully explained by comorbid substance use. Strong associations were found irrespective of sociodemographic characteristics, and for different types of accidental death (especially poisoning or falls). All mental disorders were strong independent risk factors for accidental death, which was substantially more common than suicide.


An osmoregulatory syncytium and associated cells in a freshwater mosquito.
In embryological terms the anal papillae are the product of eversion of the hindgut tissues. The rectum and the anal papillae have the same origin and have a marked structural similarity. The insect hindgut is very labile being able to produce salt transporting or 'chloride cells' from any of the tissues of which it is composed. The hindgut consists of four distinct regions: the ileum and part of the anal canal have a mechanical function, the rectum and the posterior anal canal contain transporting cells. Two new types, 'interstitial' and 'tertiary' are reported in the rectum. The structure of the anal papillae changes with increased salinity. Changes in the plasma membranes alter the surface area for transport. Changes in the number of mitochondria are not accompanied by changes in oxygen consumption. If mitochondria are the site of oxidative metabolism then their number does not control the level of oxygen consumption. In Aedes aegypti the papillary epithelium appears to be a syncytium. Across the lumen of the papillae there are cellular sheets supporting the tracheoles. At the base of the papillae there is a cellular transition zone; circular muscles in this region may be used to occlude the papillae. The control of salt transport may be hormonal.


Quantitative peptidomics to measure neuropeptide levels in animal models relevant to psychiatric disorders.
Neuropeptides play many important roles in cell-cell signaling and are involved in the control of anxiety, depression, pain, reward pathways, and many other processes that are relevant to psychiatric disorders. Mass spectrometry-based peptidomics techniques can identify the precise forms of peptides that are present in a given tissue. Utilizing this technique, peptides with any posttranslational modifications can be identified, and the exact sequence of the peptides can be determined. Unlike radioimmunoassays, which are limited by specific antibodies and often cannot discriminate between different lengths of peptides from the same precursor, peptidomics reveals the precise sequence and allows for the identification of both known and novel peptides. The use of isotopic labels allows for quantitative peptidomics, which results in the ability to compare peptide levels between differently treated samples. These tags can be synthesized in five different isotopic forms, permitting multivariate analysis of up to five different groups of tissue extracts in a single liquid chromatography/mass spectrometry run; this is ideal for measuring changes in neuropeptides in animals subjected to drug treatments, or in comparing animal models of psychiatric disorders.


Systems of care: new partnerships for community psychology.
For almost two decades, the federal government has supported the development of integrated models of mental health service delivery for children and families, known as systems of care (SOCs), that strive to be child-centered, family-focused, community-based, and culturally competent. These efforts align well with the values and principles (e.g., empowerment, collaboration, strengths emphasis, focus on macro-level social/system change) central to community psychology (CP; Kloos et al. in Community psychology, Cengage Learning, Belmont, 2012). Despite the convergence of many core values, CPs have historically been underrepresented in key roles in SOC initiatives. However, this has changed in recent years, with increasing examples of community psychology skills and principles applied to the development, implementation, and evaluation of SOCs. Because successful and sustainable implementation of SOCs requires community and system-level change, and SOCs are increasingly being urged to adopt a stronger "public health" orientation (Miles et al. in A public health approach to children's mental health: a conceptual framework, Georgetown University Center for Child and Human Development, National Technical Assistance Center for Children's Mental Health, Washington, DC, 2010), there is great potential for CPs to play important roles in SOCs. This paper discusses opportunities and roles for CPs in SOCs in applied research and evaluation, community practice, and training.


Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas.
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma. PHZ was inactive on the same cells. Similar results were obtained when cells were grown in adherence or as 3D multicellular tumor spheroids. RTV treatment but not IDV treatment induced AMP-activated protein kinase (AMPKα) phosphorylation that paralleled the decrease in glycolytic activity and cell growth. IDV, but not RTV, induced an increase in GLUT1/SLC2A1 whose activity could compensate for the inhibition of GLUT4/SLC2A4 by IDV. RTV and IDV pass poorly the blood brain barrier and are unlikely to reach sufficient liquoral concentrations in vivo to inhibit glioblastoma growth as single agents. Isobologram analysis of the association of RTV or IDV and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide (TMZ) indicated synergy only with RTV on inhibition of glioblastoma cells. Finally, we tested in vivo the combination of RTV and BCNU on established GL261 tumors. This drug combination increased the overall survival and allowed a five-fold reduction in the dose of BCNU.


Protective mechanisms of melatonin against selenium toxicity in Brassica napus: insights into physiological traits, thiol biosynthesis and antioxidant machinery.
The ubiquitous signaling molecule melatonin (N-acetyl-5-methoxytryptamine) (MT) plays vital roles in plant development and stress tolerance. Selenium (Se) may be phytotoxic at high concentrations. Interactions between MT and Se (IV) stress in higher plants are poorly understood. The aim of this study was to evaluate the defensive roles of exogenous MT (0 μM, 50 μM, and 100 μM) against Se (IV) (0 μM, 50 μM, 100 μM, and 200 μM) stress based on the physiological and biochemical properties, thiol biosynthesis, and antioxidant system of Brassica napus plants subjected to these treatments. Se (IV) stress inhibited B. napus growth and biomass accumulation, reduced pigment content, and lowered net photosynthetic rate (Pn) and PSII photochemical efficiency (Fv/Fm) in a dose-dependent manner. All of the aforementioned responses were effectively alleviated by exogenous MT treatment. Exogenous MT mitigated oxidative damage and lipid peroxidation and protected the plasma membranes from Se toxicity by reducing Se-induced reactive oxygen species (ROS) accumulation. MT also alleviated osmotic stress by restoring foliar water and sugar levels. Relative to standalone Se treatment, the combination of MT and Se upregulated the ROS-detoxifying enzymes SOD, APX, GR, and CAT, increased proline, free amino acids, and the thiol components GSH, GSSG, GSH/GSSG, NPTs, PCs, and cys and upregulated the metabolic enzymes γ-ECS, GST, and PCS. Therefore, MT application attenuates Se-induce oxidative damage in plants. MT promotes the accumulation of chelating agents in the roots, detoxifies Se there, and impedes its further translocation to the leaves. Exogenous MT improves the physiological traits, antioxidant system, and thiol ligand biosynthesis in B. napus subjected to Se stress primarily by enhancing Se detoxification and sequestration especially at the root level. Our results reveal better understanding of Se-phytotoxicity and Se-stress alleviation by the adequate supply of MT. The mechanisms of MT-induced plant tolerance to Se stress have potential implications in developing novel strategies for safe crop production in Se-rich soils.


[Impact of ageing and related factors on death rate of diabetes mellitus in Beijing].
To analyze the ageing and related risk factors affecting the death rate of diabetes mellitus in Beijing, and make a correct assessment of risk factors in changing the death rate of diabetes mellitus. The changes of death rate on diabetes mellitus in the past 10 years, from 1991 to 2000 were analyzed and calculated as to making clear what is the effects resulting from the ageing and the risk factors. The death rate of diabetes mellitus was increased to 117.55%, from 1991 to 2000, in which 53.28% were attributing to the ageing and 46.72% to the risk factors. The effects of ageing and risk factors on death rate of diabetes mellitus should be different and the ageing should be a factor more important than the other risk factors.


Evaluation of ribosomal RNA gene restriction patterns for the classification of Bacillus species and related genera.
To identify Bacillus species and related genera by fingerprinting based on ribosomal RNA gene restriction patterns; to compare ribosomal RNA gene restriction patterns-based phylogenetic trees with trees based on 16S rRNA gene sequences; to evaluate the usefulness of ribosomal RNA gene restriction patterns as a taxonomic tool for the classification of Bacillus species and related genera. Seventy-eight bacterial species which include 42 Bacillus species, 31 species from five newly created Bacillus-related genera, and five species from five phenotypically related genera were tested. A total of 77 distinct 16S rRNA gene hybridization banding patterns were obtained. The dendrogram resulting from UPGMA analysis showed three distinct main genetic clusters at the 75% banding pattern similarity. A total of 77 distinct 23S and 5S rRNA genes hybridization banding patterns were obtained, and the dendrogram showed four distinct genetic clusters at the 75% banding pattern similarity. A third dendrogram was constructed using a combination of the data from the 16S rRNA gene fingerprinting and the 23S and 5S rRNA genes fingerprinting. It revealed three distinct main phylogenetic clusters at the 75% banding pattern similarity. The Bacillus species along with the species from related genera were identified successfully and differentiated by ribosomal RNA gene restriction patterns, and most were distributed with no apparent order in various clusters on each of the three dendrograms. Our data indicate that ribosomal RNA gene restriction patterns can be used to reconstruct the phylogeny of the Bacillus species and derived-genera that approximates, but does not duplicate, phylogenies based on 16S rRNA gene sequences.


The organization of endocytotic vesicles in lymphatic endothelium.
The lymphatic endothelium from renal hilar lymphatics in the rat was subjected to qualitative and quantitative ultrastructural analysis with emphasis on the extent and disposition of its vesicular component. The uncoated endocytotic vesicles had an average maximum diameter of 0.073 micron and occupied 7% of the cytoplasm. There were approximately 21 vesicles in each cubic micrometer of cytoplasm. In standard electron microscopic preparations of glutaraldehyde-fixed endothelium 50% of the vesicles appeared to lie free within the cytoplasm. The remainder were seen to touch or open onto the luminal or abluminal surface of the endothelium. The degree to which intracytoplasmic endocytotic vesicles remained discrete or communicated with the plasma membrane was examined using tannic acid and ruthenium red. These substances specifically bind to charged molecules on the cell surface and identify membranes continuous with it. When this technique was applied to aldehyde-fixed tissue nearly 90% of the vesicles that were apparently free within the cell could be shown to retain a connection with the surface, approximately equal numbers communicating with either the luminal or abluminal surface. At least 15% of these vesicles existed as intercommunicating clusters. These results suggest that many vesicles are not simple discrete units, but rather form parts of chains that reach either luminal or abluminal surface. Thus, apparently discrete vesicles may be parts of vesicular chains cut in cross section. The possible relation between chemical fixation and this plan of vesicular organization is discussed and it is concluded that while chemical fixation may result in an overestimation of the numbers of intercommunicating vesicles, the qualitative aspects of vesicle disposition seem largely unaffected. Although the functional significance of our observations has yet to be determined, should this plan of vesicular organization apply to initial lymphatics as well, the concept of vesicular transport solely by random movement of discrete vesicles across lymphatic endothelium should be modified.


Albumin, oral contraceptives, and venous thromboembolism risk in astronauts.
A venous thromboembolism (VTE) event occurred in a female astronaut during long-duration spaceflight. Multiple factors may have contributed to this risk, including the use of combined (progestin + estrogen) oral contraceptives (cOC). Biochemistry data from 65 astronauts were evaluated for associations with cOC use and with sex. The female astronauts who used cOCs had lower concentrations of serum albumin and higher concentrations of transferrin, a protein involved in the clotting cascade, than the male astronauts and the female astronauts who were not taking cOCs (P < 0.001). The women who used cOCs had higher serum concentrations of the acute phase reactant ceruloplasmin and cortisol during flight (P < 0.001) than the men and the women who were not taking cOCs; they also had higher calculated whole blood viscosity than women not taking cOCs (P < 0.001). Lower circulating concentrations of albumin, higher concentrations of transferrin, and elevated markers of inflammation all could contribute to an increased risk of VTE during spaceflight. These changes, in association with a higher blood viscosity, can directly affect endothelial glycocalyx integrity and hypercoagulability status, both of which contribute to VTE risk in terrestrial populations.NEW & NOTEWORTHY We report here evidence of an association between oral contraceptive use and serum albumin, among other factors, which potentially increase the risk of venous thromboembolism in astronauts. These findings highlight potential risks to astronaut health while providing potential alternative countermeasures for decreasing VTE risk during spaceflight. These findings also highlight an underrecognized potential mechanism for hypoalbuminemia to increase VTE risk in terrestrial populations.


Role of Protease-Activated Receptor-1 in Glioma Growth.
Activation of a thrombin receptor, protease-activated receptor-1 (PAR-1), induces angiogenesis, cell proliferation, and invasion in tumors. The present study examined the effect of host PAR-1 gene deletion on glioma growth in a mouse model. F98 glioma cells were implanted into the right caudate of either wild type (WT) or PAR-1 knockout (KO) mice. Mice underwent magnetic resonance imaging (MRI) and the brains were used for measurements of brain water content and tumor mass. Levels of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were also measured by ELISA (enzyme-linked immunosorbent assay). We found brain water content in the ipsilateral hemisphere and the tumor mass were significantly lower in PAR-1 KO than WT mice at day 12 after implantation of F98 cells (p < 0.05). HIF-1α protein levels in the ipsilateral hemisphere were higher in the WT mice (373 ± 25 pg/g brain tissue vs 333 ± 35 pg/g brain tissue in PAR-1 KO mice, p < 0.05) 7 days after F98 cell implantation. VEGF protein levels were also higher in the ipsilateral hemisphere of WT mice (219 ± 21 vs 166 ± 22 pg/g brain tissue in PAR-1 KO mice, p < 0.01). In conclusion, PAR-1 has a role in glioma growth and could be a new therapeutic target for gliomas.


Depression in hemodialysis patients.
Psychiatric evaluation of depression in medically ill patients using DSM-III-R or Research Diagnostic Criteria (RDC) is difficult because these diagnostic systems have not been validated for this population. Diagnosis of depression has been especially problematic in patients with end-stage renal disease (ESRD). This study found a 17.7% prevalence of RDC-defined minor depression and a 6.5% prevalence of major depression in 124 ESRD patients treated with hemodialysis. Vegetative symptoms of depression were less useful for discriminating between those with and without depression than were the psychological symptoms of suicidal ideation, depressed mood, and discouragement.


Significance and Potential Role of Eosinophils in Non-Cystic Fibrosis Bronchiectasis.
Bronchiectasis is a complex and heterogeneous disease with a myriad of pulmonary and extrapulmonary etiologies. Bronchiectasis has a predominantly neutrophilic inflammatory profile. However, eosinophilic inflammation has also been documented in both the airways and the systemic circulation. Various diseases (eg, asthma, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyps) characterized by heightened type 2 airway inflammatory responses, including blood or sputum eosinophilia, may coexist with bronchiectasis. Apart from those eosinophilic etiologies or comorbidities related to bronchiectasis, around 20% of patients with bronchiectasis have peripheral eosinophilia (at least 3% or 300 eosinophils/μL) with no identified concomitant disease (also termed "eosinophilic bronchiectasis"), whose roles have not been fully understood. The two key points regarding these observations are that eosinophils confer both bactericidal and antiviral properties against common pathogenic microorganisms that are usually detected in bronchiectasis, and that eosinophilic bronchiectasis has been associated with better therapeutic response to inhaled corticosteroids and other anti-TH2 profile treatments. In this review, we summarize the most significant evidence regarding the role of eosinophils in patients with bronchiectasis, including the association of bronchiectasis with eosinophilic diseases (as etiologies or comorbidities), and existing data on eosinophilic bronchiectasis not related to eosinophilic disorders.


[Assessment of a modified Hospital Emergency Appropriateness Evaluation Protocol].
Hospital Emergency inappropriate attendances need to be evaluated, including emergencies that can be solved in primary care. The study aim was to validate a Hospital Emergency Appropriateness Evaluation Protocol (HEAEP) having into account patient health care setting. An HEAEP with explicit criteria was developed. We randomly chose 100 emergency medical records among all patients attended at the Granada Hospital Ruiz de Alda in the first quarter of 2000. Records were evaluated by six emergency specialists to compare results provided by the HEAEP. The HEAEP identified as appropriate all attendances so classified by experts. As inappropriate, HEAEP only pointed out 69% of the emergency visits considered as inappropriate by experts. The modified HEAEP shown a good internal validity and high reproducibility. The main advantage is to point out as inappropriate emergency attendances that can be solved in primary care.


Impaired peripheral Th1 CD4+ T cell response to Escherichia coli proteins in patients with Crohn's disease and ankylosing spondylitis.
To clarify the impact of T cell responses towards enteric antigens for chronic intestinal inflammation, we determined T helper 1 reactivity towards conserved Escherichia coli proteins in patients with Crohn's disease (CD) and healthy individuals and patients with ankylosing spondylitis (AS), who also often show microscopic inflammatory lesions within the gut or even develop overt inflammatory bowel disease. We determined the frequency of IFNγ+CD40L+ cells/CD4+ T cells after stimulation of whole blood with pools of E. coli proteins. The E. coli-specific Th1 response was significantly reduced in CD patients and to a lower extent also in AS patients. E. coli is a target for polyclonal Th1 responses in healthy individuals. The impairment of these responses in CD and AS patients might be due to recruitment of enterobacteria-specific Th1 cells to the gut or might reflect inadequate priming of adaptive immune response.