Studies of complement activation and IgG subclass restriction of anti-thyroglobulin.
Using a sensitive radioimmunoassay, it was demonstrated that autoantibodies to human thyroglobulin (hTg) did not activate complement upon interaction with solid phase adsorbed hTg. Since IgG4 immunoglobulins do not activate complement, we studied sera containing large amounts of anti-thyroglobulin (anti-Tg) with a sensitive radioimmunoassay for IgG4 anti-Tg. Antibodies of the IgG4 subclass were detected in the sera of each of the eight patients studied and not in control subjects. Quantitative assays of IgG4 anti-Tg were performed by comparing the removal of anti-Tg and total IgG4 during immunoadsorption of anti-Tg. The contribution of IgG4 anti-Tg antibodies to the total quantity of anti-Tg ranged from 6 to 30%, an amount inadequate to explain the lack of complement activation by anti-Tg.


The risks of biomarker-based epidemiology: Associations of circulating calcium levels with age, mortality, and frailty vary substantially across populations.
Recent studies have shown contradictory associations between calcium levels and health outcomes. We suspected these conflicting results were the consequence of more general issues with how biomarkers are analyzed in epidemiological studies, particularly in the context of aging. To demonstrate the risks of typical analyses, we used three longitudinal aging cohort studies and their demographic subsets to analyze how calcium levels change with age and predict risk of mortality and frailty. We show that calcium levels either increase or decrease with age depending on the population, and positively or negatively predict frailty depending on the population and analysis; both age and frailty results showed substantial heterogeneity. Mortality analyses revealed few significant associations but were likely underpowered. Variation in population composition (demographics, diseases, diet, etc.) leads to contradictory findings in the literature for calcium and likely for other biomarkers. Epidemiological studies of biomarkers are particularly sensitive to population composition both because biomarkers generally have non-linear and often non-monotonic relationships with other key variables, notably age and health outcomes, and because there is strong interdependence among biomarkers, which are integrated into complex regulatory networks. Consequently, most biomarkers have multiple physiological roles and are implicated in multiple pathologies. We argue that epidemiological studies of aging using biomarkers must account for these factors, and suggest methods to do this.


Therapeutic effects of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cell transplantation on established autoimmune thyroiditis.
This study aimed to identify the beneficial effects of adipose tissue-derived mesenchymal stem cells (ASCs) and ASCs that overexpress the CTLA4Ig gene (CTLA4Ig-ASCs) on established autoimmune thyroiditis and to examine changes in clinical chemistry parameters and the presence of humoral responses upon repeated long-term administration of autologous ASCs. This study also aimed to acquire desirable results in a preclinical study by using large-sized lab animals and applying ASCs that overexpress therapeutic genes. Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Experimental dogs were divided into five groups: (i) ASC IT + IV, (ii) ASC IV, (iii) CTLA4Ig-ASC IT + IV, (iv) CTLA4Ig-ASC IV, and (v) control IT + IV (saline only), and they received intrathyroidal (IT; 10 million cells/250 µl saline per thyroid) administration one time or intravenous (IV; 20 million cells/5 ml) administration seven times within a 101-day period. Blood samples were collected every week, and thyroids were harvested on days 104-106. After serial ASC or CTLA4Ig transplantation, the levels of canine thyroglobulin autoantibodies (TgAA) in serum and the infiltration of T-lymphocytes between the follicles of the thyroid glands were decreased. The expression of FoxP3 in submandibular lymph nodes was significantly increased. Repeated long-term administration of autologous ASCs or CTLA4Ig-ASCs did not generate changes in clinical chemistry parameters or humoral responses.The TgAA test can detect autoimmune thyroiditis years before clinical signs of hypothyroidism occur. Thus, ASC and CTLA4Ig-ASC transplantation in that period can be attractive candidates to ameliorate autoimmune thyroiditis and prevent the development of hypothyroidism.


Effective medium theory for mechanical phase transitions of fiber networks.
Networks of stiff fibers govern the elasticity of biological structures such as the extracellular matrix of collagen. These networks are known to stiffen nonlinearly under shear or extensional strain. Recently, it has been shown that such stiffening is governed by a strain-controlled athermal but critical phase transition, from a floppy phase below the critical strain to a rigid phase above the critical strain. While this phase transition has been extensively studied numerically and experimentally, a complete analytical theory for this transition remains elusive. Here, we present an effective medium theory (EMT) for this mechanical phase transition of fiber networks. We extend a previous EMT appropriate for linear elasticity to incorporate nonlinear effects via an anharmonic Hamiltonian. The mean-field predictions of this theory, including the critical exponents, scaling relations and non-affine fluctuations qualitatively agree with previous experimental and numerical results.


Quality of life for patients with epithelial ovarian cancer.
Ovarian cancer is the sixth most common cancer worldwide and the seventh most common cause of deaths from cancer in women. Recent annual worldwide figures reflect 204,000 new cases of ovarian cancer and 125,000 deaths. Treatment of advanced ovarian cancer involves a combination of surgery and chemotherapy, both of which may impact a woman's physical, social, and emotional well-being. A woman's quality of life (QOL) is affected by disease site, and treatment-specific and patient-specific factors, but other common QOL issues include changes in physical functioning owing to side effects of treatment, psychological distress caused by fear and anxiety of recurrence, sexual dysfunction associated with anatomic and physiologic changes of treatment, and for younger women, loss of childbearing potential. As new diagnostic and treatment strategies for gynecologic malignancies are developed, research efforts should include QOL consequences. Further studies are needed to develop strategies for identifying women at risk for serious QOL disruption so that effective interventions to assist these women can be designed.


Thyroid hormone and the kidney.
Thyroid hormones affect both renal morphology and function. They are required for kidney growth and development, and thyroid deficiency results in decreased renal plasma flow and glomerular filtration rate and in impaired urinary concentration and dilution. Thyroid hormones also influence membrane transport and electrolyte metabolism, and alterations in mineral metabolism in hyperthyroidism frequently cause calcium nephropathy which affects renal function adversely. The kidney plays an important role in the peripheral metabolism of iodine and thyroid hormones, and thyroid function is altered in certain kidney diseases, particularly chronic renal failure. The pathogenesis of these alterations is currently under active investigation.


Psychosocial correlates of exercise in women with self-reported depressive symptoms.
Exercise effectively reduces symptoms of depression. However, correlates of regular exercise in depressed women are unknown. This study assessed psychosocial determinants of exercise in a sample of women with depressive symptoms. Sixty-one women completed demographic, depression, and exercise-related questionnaires. The average Primary Health Questionnaire-9 (PHQ-9) depression score was 12.1 (SD = 5.0), indicating moderate depressive symptoms. In the previous week, the women reported 12.8 metabolic equivalents (METs) of exercise. Low levels of self-efficacy and social support for exercise were also reported. Depressive symptoms were positively associated with barriers to exercise (r = .35, P < .01), and barriers were inversely related to exercise METs (r = -.37, P < .05). Barriers to activity and education level were significant determinants of exercise. Women with depressive symptoms report minimal exercise involvement, numerous barriers to exercise, and low exercise self-efficacy and social support for exercise.


The prevalence and age-related characteristics of pain in a sample of women veterans receiving primary care.
Women veterans are a growing but understudied population believed to be at increased risk for pain problems. Because of risk factors and clinical observations, we hypothesized that women veterans might have a high prevalence of pain and, thus, sought to determine the prevalence of (and age-related variations in) pain and to characterize several key pain dimensions in a sample of women veterans. Women with routine appointments at the VA Connecticut Women's Health Center were recruited for study. Participants completed a 59-item questionnaire that provided information about their demographic, clinical, and pain status, as well as use of health services. Of 236 women approached, 213 (89%) completed the questionnaire. The mean age was 52 years, and most (78%) reported an ongoing pain problem. For those reporting pain, the mean duration of pain was 6 years, average pain intensity was 6.3 (range 1-10), and commonly endorsed pain sites included lower extremity (68%), low back (63%), and shoulder (48%). The most frequently endorsed treatment (by 80%) was analgesic medication use. Across the four age categories (20-35, 36-50, 51-65, and > or =66 years), pain prevalences were 64%, 89%, 83%, and 69%, respectively. Although pain intensity levels did not vary across age groups, older women (> or =66) reported using fewer pain treatments, including analgesic medications. Finally, those with (vs. those without) pain reported a greater number of medical and mental health visits in the preceding year. This study documented a significantly high prevalence of pain among a sample of women veterans receiving primary care in a VA women's health clinic.


On-road facility to measure and characterize emissions from heavy-duty diesel vehicles.
In response to lingering concerns about the utility of dynamometer data for mobile source emissions modeling, the U.S. Environmental Protection Agency (EPA) has constructed an on-road test facility to characterize the real-world emissions of heavy-duty trucks. The facility was designed to effectively demonstrate the full range of vehicle operation and to measure the emissions produced. Since it began operation, the facility has been continuously upgraded to incorporate state-of-the-art technology. Its potential uses include collecting modal emissions data, validating dynamometer test parameters and results, and demonstrating new emission control technologies.


Iliopsoas hematoma associated with low-molecular-weight heparin use: A case report.
Iliopsoas hematoma is an uncommon clinical entity that may develop in association with anticoagulation states, coagulopathies and hemodialysis, or anticoagulant therapy. Here, we report a case of unilateral iliopsoas hematoma in a 60-year-old man who received low-molecular-weight heparin for anticoagulation due to continuous veno-venous hemofiltration. The patient presented with fever and productive cough for 2 days. He received continuous veno-venous hemofiltration due to rising blood urea nitrogen (22.7 mmol/L; normal references: 3.2-7.1 mmol) and creatinine (1345 µmol/L; normal references: 53-106 µmol/L). Low-molecular-weight heparin (enoxaparin, 3500-5500 Da, 5-10 IU/kg/h) was delivered continuously by pumps for anticoagulation therapy. At day 12 post heparin treatment, the patient complained left back pain. Platelet count (243 × 109/L) was normal, but both activated partial thromboplastin time (67.5 s) and prothrombin time (17.3 s) were prolonged. Abdominal computed tomography scan revealed left iliopsoas swelling with an indistinct border. Low-molecular-weight heparin was discontinued. Anti-Xa was not monitored throughout the treatment. No improvement was seen, and 3 days later, the patient died after his family decided to terminate therapy. This case highlights the needs for careful anticoagulation as well as close monitoring, and particularly the use of anti-Xa to guide the treatment.


Disparities in organ allocation and access to liver transplantation in the USA.
Liver transplantation has become the standard of care for the treatment of chronic liver disease. In 1986, the United Network for Organ Sharing (UNOS) was formed to ensure the just and equitable allocation of donor livers. At the time, UNOS decided to use the Childs-Turcotte-Pugh scoring system to determine the degree of liver disease in potential transplant patients. Unfortunately, it was shown that the Childs-Turcotte-Pugh system was easily manipulated and did not provide equal access to donor organs. Owing to this fact, the Model of End Stage Liver Disease (MELD) score was instituted by UNOS in February 2002. While the institution of MELD has shown an improvement in organ allocation and outcomes, disparities still exist. This article discusses UNOS and the MELD allocation system as well as the racial, geographic and gender disparities that occur despite the institution of the MELD system.


Characterization of a supernumerary marker derived from chromosome 17 by microdissection in an adult with MR/MCA.
We describe a 38-year-old adult who has a supernumerary marker chromosome in 40% of metaphase cells which was identified by reverse in situ hybridization with a DNA probe made by microdissection to be derived from chromosome 17. The breakpoints are estimated by G-banding and fluorescence in situ hybridization (FISH) to consist of the region from 17p11.1 to proximal 17q21. The propositus displayed severe growth retardation, kyphoscoliosis, bilateral cataracts, severe calcaneovalgus deformity of the feet, dysmorphic facies, profound mental retardation, and multiple medical problems requiring ongoing medical management. These problems included a mitral valve prolapse with regurgitation, recurrent upper and lower respiratory tract infections, and severe respiratory insufficiency. The relatively long survival of this patient enabled us to describe the natural history of this rare chromosomal mutation.


Preoperative Altered Spontaneous Brain Activity and Functional Connectivity Were Independent Risk Factors for Delayed Neurocognitive Recovery in Older Adults Undergoing Noncardiac Surgery.
Recently, it has been demonstrated that patients with subtle preexisting cognitive impairment were susceptible to delayed neurocognitive recovery (DNR). This present study investigated whether preoperative alterations in gray matter volume, spontaneous activity, or functional connectivity (FC) were associated with DNR. This was a nested case-control study of older adults (≥60 years) undergoing noncardiac surgery. All patients received MRI scan at least 1 day prior to surgery. Cognitive function was assessed prior to surgery and at 7-14 days postsurgery. Preoperative gray matter volume, amplitude of low-frequency fluctuation (ALFF), and FC were compared between the DNR patients and non-DNR patients. The independent risk factors associated with DNR were identified using a multivariate logistic regression model. Of the 74 patients who completed assessments, 16/74 (21.6%) had DNR following surgery. There were no differences in gray matter volume between the two groups. However, the DNR patients exhibited higher preoperative ALFF in the bilateral middle cingulate cortex (MCC) and left fusiform gyrus and lower preoperative FC between the bilateral MCC and left calcarine than the non-DNR patients. The multivariate logistic regression analysis showed that higher preoperative spontaneous activity in the bilateral MCC was independently associated with a higher risk of DNR (OR = 3.11, 95% CI, 1.30-7.45; P = 0.011). A longer education duration (OR = 0.57, 95% CI, 0.41-0.81; P = 0.001) and higher preoperative FC between the bilateral MCC and left calcarine (OR = 0.40, 95% CI, 0.18-0.92; P = 0.031) were independently correlated with a lower risk of DNR. Preoperative higher ALFF in the bilateral MCC and lower FC between the bilateral MCC and left calcarine were independently associated with the occurrence of DNR. The present fMRI study identified possible preoperative neuroimaging risk factors for DNR. This trial is registered with Chinese Clinical Trial Registry ChiCTR-DCD-15006096.


Management of apathy in nursing homes using a teaching program for care staff: the STIM-EHPAD study.
This study aimed to evaluate the effectiveness of a nursing home (NH) staff education to manage apathy in older individuals with a diagnosis of dementia. Sixteen NHs agreed to participate, and 230 demented apathetic residents were randomly assigned to the reference group (RG) or the intervention group (IG). IG received a month of weekly 4-h training. Qualitative evaluation was performed through interviews and questionnaires regarding work practices and knowledge about dementia. Quantitative evaluation was at baseline, at the end of the training program (week 4), and 3 months after the end of it with the use of the Neuropsychiatric Inventory (NPI), the Apathy Inventory, and two observation scales. In the qualitative evaluation, very few staff responded to the questionnaire. Concerning the difficulty that managing residents' behavioral symptoms presented, aggressiveness was ranked as the most difficult behavior to manage and apathy as the least difficult. In the quantitative evaluation, the results are as follows. NPI: the IG scores increased from baseline to week 4 more than the RG for symptoms belonging to the affective and the psychotic NPI item subgroup. Apathy Inventory: there was a significant decrease of the emotional blunting score dimension in the IG. Group Observation Scale: significant improvement was observed for the emotional blunting dimension in the IG only. Apathy is rarely identified as a problem in NH. Emotional blunting was the only dimension sensitive to change. Failure to improve residents' level of interest could be explained by the difficulties encountered in accessing information regarding the subjects' personal interests. But it remains possible to modify residents' emotional reactivity and staff's perceptions of residents' behaviors and emotions.


Enrichment versus biofilm culture: a functional and phylogenetic comparison of polycyclic aromatic hydrocarbon-degrading microbial communities.
The effect that culture methods have on the diversity of degradative microbial communities is not well understood. We compared conventional batch enrichment with a biofilm culture method for the isolation of polycyclic aromatic hydrocarbon (PAH)-degrading microbial communities from a PAH-contaminated soil. The two methods were assessed by comparing: (i) the diversity of culturable bacteria; (ii) the diversity of PAH-catabolic genes in isolated bacteria; (iii) the inter- and intraspecific diversity of active PAH-catabolic gene classes; (iv) the diversity of bacteria present in 16S rRNA gene libraries generated from RNA extracted from the two communities and soil; and (v) the estimated diversity of active bacteria in the soil and culture systems. Single-strand conformation polymorphism analysis showed that the biofilm culture yielded 36 bacterial and two fungal species compared with 12 bacterial species from the enrichment culture. Application of accumulation and non-parametric estimators to clone libraries generated from 16S rRNA confirmed that the biofilm community contained greater diversity. Sequencing of clones showed that only species from the Proteobacteria were active in the enrichment culture, and that these species were expressing an identical nahAc-like naphthalene dioxygenase. 16S rRNA clones generated from the biofilm community indicated that species from the Cytophaga/Flavobacterium, high G+C bacteria and Proteobacteria were active at the time of sampling, expressing cndA-, nahAc- and phnAc-like naphthalene dioxygenases. The diversity of active species in the biofilm culture system closely matched that in the PAH-contaminated source soil. The results of this study showed that biofilm culture methods are more appropriate for the study of community-level interactions in PAH-degrading microbial communities. The study also indicated that cultivation of microbial communities on solid media might be the primary source of bias in the recovery of diverse species.


Structures of the promoter and operator of the glpD gene encoding aerobic sn-glycerol-3-phosphate dehydrogenase of Escherichia coli K-12.
The nucleotide sequence of a 690-base-pair DNA segment containing the control region for the glpD gene encoding aerobic sn-glycerol-3-phosphate dehydrogenase was determined. An ATG translation initiation codon with an adjacent ribosome-binding site was found which preceded an open reading frame continuing 61 codons to the end of the DNA that was sequenced. The start site for transcription, identified by using primer extension analysis, was located 42 base pairs upstream from the proposed Met start codon. The transcription start site was preceded by a region containing typical -10 and -35 sequences found in bacterial promoters. A binding site for the cyclic AMP-cyclic AMP receptor protein complex (identified by comparison with the consensus-binding sequence and verified by using DNase I footprinting) was located just upstream from the -35 sequence, centered at position -63. The interaction site for the glp repressor was identified by using DNase I footprinting. It consisted of a 49-base-pair region which started at the -10 sequence and continued to position +38. This region contained two directly repeated sequences, each possessing hyphenated dyad symmetry, which suggests that the operator is tandemly repeated. The presence of two adjacent operators may explain why expression of the glpD gene is the most sensitive to repressor when compared with expression of the other operons that are members of the glp regulon.


Gene expression and biomarkers in renal transplant ischemia reperfusion injury.
The incidence of postischemic acute renal allograft failure (ARF) occurs in roughly 25% of cadaveric donor kidney recipients. This high rate remained virtually unchanged over the last decades despite modification in recipient management and modern immunosuppressive strategies. It has recently been shown that among other reasons, the systemic inflammation in the brain death cadaveric organ donor contributes to subsequent ARF in the recipient. This review focuses on the consequences of ischemia and reperfusion on the cellular level and offers potential solutions for the reduction of ARF. Genome-wide gene expression analysis together with sophisticated biostatistical analysis made it possible to identify several candidate gene products and proteins that may act as specific and sensitive biomarker for renal inflammation and ischemia. These markers may be very helpful in the clinical management of patients with a high a priori risk of subsequent ARF such as recipients of marginal donor kidneys. Ongoing clinical trials will evaluate whether immunosuppression of the cadaveric organ donor before organ harvest will have the potential to reduce inflammation in the transplant kidney and subsequently lead to a reduction in the rate of ARF.


Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer.
Bladder cancer is a common malignancy in the United States. Although urine cytology is a useful adjunct in both diagnosis and follow-up and is highly sensitive for detecting high-grade tumors, it is limited by decreased sensitivity in detecting low-grade tumors, which constitute the majority of new diagnoses. Additional screening tests with high sensitivity and specificity for urothelial tumors of all grades are indicated to help improve the diagnostic ability of urine cytology as well as to reduce the need for frequent cystoscopies, especially in those with low-risk disease. Several assays have been developed, with the ImmunoCyt/uCyt+ test (DiagnoCure, Inc., Québec, Canada) being especially promising. Recent studies on the applicability and efficacy of ImmunoCyt/uCyt+ testing are reviewed, as are its sensitivity, specificity, and predictive value in the follow-up and screening of urothelial malignancies.


Insulin-degrading enzyme haplotypes affect insulin levels but not dementia risk.
Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia. We examined the association of IDE haplotypes with dementia and insulin levels in a single well-characterized cohort of Japanese-American men born between 1900 and 1919 and followed since 1965. In 1991, a fasting insulin was obtained; dementia cases were ascertained in 1991 and 1994 in a multi-stage procedure, diagnoses were made according to international guidelines. Five single-nucleotide polymorphisms were genotyped and used for haplotype analysis in a sample of 179 Alzheimer's disease cases, 104 vascular dementia cases and 516 controls nested in the total cohort. The global test for the haplotype effect on insulin levels was significant (p < 0.0001), adjusting for age, education, apolipoprotein epsilon4 status and fasting glucose. There was no association of IDE haplotypes with the risk of dementia. This study suggests IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimer's.


Differential effects of cocaine on extracellular signal-regulated kinase phosphorylation in nuclei of the extended amygdala and prefrontal cortex of psychogenetically selected Roman high- and low-avoidance rats.
Roman high (RHA)- and low (RLA)-avoidance rats are selectively bred for rapid vs. poor acquisition of active avoidance, respectively, and differ markedly in emotional reactivity, coping style, and behavioral and neurochemical responses to morphine and psychostimulants. Accordingly, acute cocaine induces more robust increments in locomotion and dopamine output in the nucleus accumbens shell (AcbSh) of RHA than of RLA rats. Cocaine induces short- and long-term neuronal plasticity via activation of the extracellular signal-regulated kinase (ERK) pathway. This study compares the effects of acute cocaine on ERK phosphorylation (pERK) in limbic brain areas of Roman rats. In RHA but not RLA rats, cocaine (5 mg/kg) increased pERK in the infralimbic prefrontal cortex and AcbSh, two areas involved in its acute effects, but did not modify pERK in the prelimbic prefrontal cortex and Acb core, which mediate the chronic effects of cocaine. Moreover, cocaine failed to affect pERK immunolabeling in the bed nucleus of stria terminalis pars lateralis and central amygdala of either line but increased it in the basolateral amygdala of RLA rats. These results extend to pERK expression previous findings on the greater sensitivity to acute cocaine of RHA vs. RLA rats and confirm the notion that genetic factors influence the differential responses of the Roman lines to addictive drugs. Moreover, they support the view that the Roman lines are a useful tool to investigate the molecular underpinnings of individual vulnerability to drug addiction.


Overexpression of the sis oncogene in a canine osteosarcoma cell line.
Specific oncogenes that contribute to the pathogenesis of canine osteosarcoma (OS) have not been identified. In the process of characterizing four OS cell lines, we have found one cell line, CO8, that overexpresses the sis oncogene, which encodes the platelet-derived growth factor (PDGF)-beta. The expression of an important downstream transcriptional target of the PDGF signaling pathway, c-myc, is also elevated fourfold. Conditioned medium from CO8 alone specifically induces tyrosine phosphorylation and therefore the activation of the PDGF-alpha and PDGF-beta receptors on murine 3T3 cells. All of the canine OS lines tested contain PDGF receptors and therefore are capable of responding to PDGE Given the importance of PDGF in promoting cell proliferation, migration, and cell survival, the activation of the sis oncogene and the resultant growth factor autocrine loop potentially contribute to the pathogenesis of a subset of canine osteosarcomas.


Provisional bifurcation stenting.
Obstructive coronary lesions involving a branch origin or extending into the branch itself, remain one of the main challenges in the rapidly developing world of interventional cardiology. Acutely, these lesions are prone to the complications resulting in significant residual stenosis or loss of one of the branches. Long-term follow up has also been disappointing with a high incidence of restenosis. Numerous techniques have been developed, aimed at optimizing the acute and long-term results by adapting standard angioplasty hardware, with limited success, particularly in the long term. This article describes a fully dedicated system for bifurcation lesions with stenting of the main vessel to the main branch, yet ensuring side branch patency, with limited risk of branch origin stenosis or stent jailing, allowing for provisional stenting of the branch as dictated by the angiographic outcome.


A cross-sectional study of prevalence and etiology of signs and symptoms of temporomandibular disorders in high school and university students.
The aim of this study was to evaluate the prevalence and need for treatment of temporomandibular disorders (TMD) in students living in Bauru, Brazil. The role of occlusal and emotional factors was also addressed. The presence and severity of TMD was determined by using a self-reported anamnestic questionnaire composed of 10 questions regarding common TMD symptoms. The symptoms were transposed into a severity classification according to the number and frequency of positive responses. Occlusal evaluation included an analysis of retruded contact position, intercuspal position, anterolateral guidance, and nonworking side contacts during mandibular movements. Palpation of the muscles and temporomandibular joints were performed to detect clinical signs of TMD. A chi square test was used to compare clinical and occlusal data with the presence and severity of TMD. A total of 0.65% of the subjects had severe TMD symptoms, 5.81% had moderate symptoms, and 34.84% had mild symptoms. Those with severe and moderate symptom levels were interpreted to be in need of treatment. Symptoms were found significantly more frequently in females than in males (P < .01). Self-reported emotional tension and parafunctional habits demonstrated strong associations with TMD (P < .01). Occlusion did not seem to influence the presence or severity of TMD. Based on these results, the efficacy of some traditional TMD treatments should be reconsidered, and reversible and conservative procedures should be the first choice for managing TMD patients.


High-performance ZnCo₂O₄@CeO2₂₄ core@shell microspheres for catalytic CO oxidation.
In this paper, we report a self-assembly method to synthesize high-quality ZnCo2O4@CeO2 core@shell microspheres with tunable CeO2 thickness. ZnCo2O4 spheres were first synthesized as the core, followed by a controlled CeO2 shell coating process. The thickness of CeO2 shell could be easily tuned by varying the feeding molar ratio of Ce/Co. Transmission electron microscope (TEM) images and scanning transmission electron microscope (STEM) image have identified the core@shell structure of these samples. In CO oxidation tests these ZnCo2O4@CeO2 core@shell microspheres exhibited promising catalytic performance, and the catalytic activity of the best sample is even close to the traditional noble metal-CeO2 system, attaining 100% CO conversion at a relatively low temperature of 200 °C. Cycling tests confirm their good stability of these core@shell microspheres besides activity. Their high catalytic performance should be attributed to the core@shell structure formation, and moreover further H2-temperature-programmed reduction (TPR) results revealed the possible synergistic effects between the two components of ZnCo2O4 and CeO2.


Influence of dialysis on prednisolone kinetics.
Six patients with end-stage renal disease were given prednisolone, 0.7-1.0 mg/kg/b.wt. parenterally. Prednisolone kinetics were investigated during dialysis, in 3 patients on hemodialysis and in 3 on continuous peritoneal dialysis, and also on days without dialysis. Mean plasma half-life was 250 min in five patients and 690 min in one patient who also suffered from intermittent porphyria. No change was found in prednisolone kinetics when the dialysis-free period was compared to the dialysis periods.


In vitro and in vivo activity of 3-(1-methyl 1-5-nitro-2-imidazolylmethylideneamino)-2-oxazolidinone against Pasteurella.
Furazolidone was more active than 3-(1-methyl)-5-nitro-2-imidazolyl-methylideneamino)-2-oxazolidinone (MABN) against a series of 34 isolates of Pasteurella and 11 of Yersinia (formerly designated Pasteurella). However, the nitroimidazole was superior to furazolidone by both subcutaneous and oral routes against a series of mouse infections incited by strains of Pasteurella. It also was superior to furazolidone and sulfaquinoxaline when administered in the diet against two Pasteurella strains in a fowl cholera model infection in chickens. The good in vitro activity of MABN plus its low toxicity suggest its further study as an agent for fowl cholera and the shipping fever complex of cattle.


Immunohistological analysis of CD1a langerhans cells and CD57 natural killer cells in healthy and diseased human gingival tissue: A comparative study.
Cell interaction between dendritic cells (DC) and natural killer (NK) cells in the periodontal milieu is not yet fully known, although these cells are individually known to contribute to the pathogenesis of periodontal disease. Fifty subjects (25 males and 25 females) were included in the study. The subjects were divided into three groups: Group A comprised 16 subjects with clinically healthy gingiva; group B 17 subjects with gingivitis; and group C 17 subjects with gingivitis; and group C 17 subjects with moderate periodontitis (PPD >/= 5 mm and CAL >/= 3 mm in at least six sites). Gingival samples were collected and immunohistochemical study was done using CD57 and CD1a antibody. Statistical analysis was done using analysis of variance (ANOVA), followed by Tukey-Kramer multiple comparison for CD1a and Tukey's highly significant difference (HSD) test for CD57. The study showed an inverse relationship between the CD1a(+) (langerhans) cells and CD57(+) (natural killer) cells. There was a significant increase in CD57(+) cells and reduction in CD1a levels as periodontal disease progressed. The significant reduction in CD1a levels in periodontal disease when compared to health could possibly be a result of NK cells down regulating it. Reduction in CD1a levels may result in a low inflammatory response subsequently resulting in tissue destruction.


A method for reducing the time required to match protein sequences with tandem mass spectra.
An algorithm for reducing the time necessary to match a large set of peptide tandem mass spectra with a list of protein sequences is described. This algorithm breaks the process into multiple steps. A rapid survey step identifies all protein sequences that are reasonable candidates for a match with a set of tandem mass spectra. These candidates are then used as models, which are refined by detailed analysis of the set of tandem mass spectra for evidence of incomplete enzymatic hydrolysis, non-specific hydrolysis and chemical modifications of amino acid residues resulting from either post-translational modifications or sample handling. Compared with current one-step methods for matching proteins to mass spectra, this multiple-step method can decrease the time required for the calculation by several orders of magnitude.


Complement Alternative Pathway׳s Activation in Patients With Lupus Nephritis.
The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed. Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = -0.412, P < 0.001 and r = -0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group. Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.


Actuating critical care therapeutics.
Viewing the intensive care unit (ICU) as a control system with inputs (patients) and outputs (outcomes), we focus on actuation (therapies) of the system and how to enhance our understanding of status of patients and their trajectory in the ICU. To incorporate the results of these analytics meaningfully, we feel that a reassessment of predictive scoring systems and of ways to optimally characterize and display the patient's "state space" to clinicians is important. Advances in sensing (diagnostics) and computation have not yet led to significantly better actuation, and so we focus on ways that data can be used to improve actuation in the ICU, in particular by following therapeutic burden along with disease severity. This article is meant to encourage discussion about how the critical care community can best deal with the data they see each day, and prepare for recommendations that will inevitably arise from application of major federal and state initiatives in big data analytics and precision medicine.


A Comparative Study of Abnormal Heating Composite Insulators.
The abnormal heating of composite insulators on transmission lines frequently occurs, seriously threatening the power grid's safe and stable operation. For different types of abnormal heating composite insulators, undifferentiated replacement wastes a lot of labor and material resources. This study explores the abnormal heating composite insulators under different environmental humidity and wind speed conditions. The heating and discharge of composite insulators are observed, and the heating range, heating shape, and temperature rise (ΔT) are analyzed. The abnormal heating of the sheath-aging composite insulator is related to the aging of the silicone rubber and the environmental humidity. The partial discharge caused by the core rod's defect is the primary source of the temperature rise in the decay-like insulator. The heating range of the contaminated insulator is connected to the environmental humidity, and the ΔT increases with the salt density. The ΔT and heating range of the three types of abnormal heating increase with the ambient humidity. The heating phenomenon under low humidity is an important characteristic that distinguishes decay-like and contaminated insulators from sheath-aging insulators. Therefore, the on-site infrared inspection should be carried out in sunny and windless weather to prevent the impact of high humidity and wind speed on infrared temperature measurement.


Does the presence of endometriosis cause a challenge for transvaginal oocyte retrieval? A comparison between patients with and without endometriosis
The aim of the study was to compare patients with and without endometriosis regarding performance rates, difficulties, and complications associated with transvaginal oocyte retrieval (TVOR) procedures. A prospective cohort study was conducted at the In Vitro Fertilization Unit of the Division of Reproductive Endocrinology and Infertility Department of a university hospital. Fifty-eight patients with endometriosis and 61 patients without endometriosis underwent TVOR procedures consecutively. Primary outcome measures were; number of needle entries per patient and performance rating defined as the total number of oocytes retrieved per vaginal needle entry. The requirement for manual compression of the abdominal wall (assistance) to reach the ovaries, procedure-related pain, and procedural complications were also evaluated. The median number of needle entries through the vaginal wall per patient was comparable between the two groups (p=0.45). Performance rates were higher in the control group (p=0.001). Performance rates and total number of the needle entries through the vaginal wall were not significantly correlated with ovarian endometrioma (OMA) diameter (r=0.28; p=0.68; r=0.275, p=0.068, respectively) in the endometriosis group. Body mass index (BMI) scores were found to be correlated with the number of the needle entries and higher BMI scores were associated with higher numbers of vaginal wall punctures (p<0.001). The requirement for manual compression of the abdominal wall was significantly higher in the control group (57.4% vs 27.6%, p=0.001). A similar proportion of women needed analgesic medications after the TVOR procedure in both groups (10.3% vs 16.4%, p=0.33). Hospital readmissions for any symptoms were also comparable between the two groups (p=0.22). Three women were treated for pelvic infection, all of whom were in the endometriosis group. Endometriosis seems to cause a challenge for TVOR that may have reflection on individual surgeon's performance rates for the procedure, independently from the diameter of a pre-existing OMA or ovarian adhesions. Obesity is another factor that may present a challenge for the procedure.


Unsupervised Facial Action Representation Learning by Temporal Prediction.
Due to the cumbersome and expensive data collection process, facial action unit (AU) datasets are generally much smaller in scale than those in other computer vision fields, resulting in overfitting AU detection models trained on insufficient AU images. Despite the recent progress in AU detection, deployment of these models has been impeded due to their limited generalization to unseen subjects and facial poses. In this paper, we propose to learn the discriminative facial AU representation in a self-supervised manner. Considering that facial AUs show temporal consistency and evolution in consecutive facial frames, we develop a self-supervised pseudo signal based on temporally predictive coding (TPC) to capture the temporal characteristics. To further learn the per-frame discriminativeness between the sibling facial frames, we incorporate the frame-wisely temporal contrastive learning into the self-supervised paradigm naturally. The proposed TPC can be trained without AU annotations, which facilitates us using a large number of unlabeled facial videos to learn the AU representations that are robust to undesired nuisances such as facial identities, poses. Contrary to previous AU detection works, our method does not require manually selecting key facial regions or explicitly modeling the AU relations manually. Experimental results show that TPC improves the AU detection precision on several popular AU benchmark datasets compared with other self-supervised AU detection methods.


Combinatorial therapy with three-dimensionally cultured adipose-derived stromal cells and self-assembling peptides to enhance angiogenesis and preserve cardiac function in infarcted hearts.
Even though stem cell therapy is a promising angiogenic strategy to treat ischaemic diseases, including myocardial infarction (MI), therapeutic efficacy is limited by low survival and retention of transplanted cells in ischaemic tissues. In addition, therapeutic angiogenesis depends on stimulating host angiogenesis with paracrine factors released by transplanted cells rather than on direct blood vessel formation by transplanted cells. In the present study, to overcome these limitations and to enhance the therapeutic efficacy of MI treatment, combinatorial therapy with three-dimensional cell masses (3DCMs) and self-assembling peptides (SAPs) was tested in a rat MI model. Spheroid-type 3DCMs, which are vascular differentiation-induced cells, were prepared by culturing human adipose-derived stromal cells on a fibroblast growth factor-immobilized surface. The SAPs were used as the carrier material to increase engraftment of transplanted cells. After coronary artery ligation, 3DCMs were combined with SAPs and were transplanted into ischaemic lesions. The therapeutic potential was evaluated 4 weeks after treatment. By combining 3DCMs and SAPs, survival and retention of transplanted cells increased threefold when compared with treatment with 3DCMs alone and transplanted cells established vascular networks in infarcted hearts. In addition, the size of the infarct in the 3DCM + SAP group was reduced to 6.09 ± 2.83% by the promotion of host angiogenesis and cardiac function was preserved, as demonstrated by a 54.25 ± 4.42% increase in the ejection fraction. This study indicates that combinatorial therapy with 3DCM and SAPs could be a promising strategy for therapeutic angiogenesis to treat MI. Copyright © 2016 John Wiley & Sons, Ltd.


Chirality in nonlinear optics.
The past decade has witnessed the emergence of new measurement approaches and applications for chiral thin films and materials enabled by the observations of the high sensitivity of second-order nonlinear optical measurements to chirality. In thin films, the chiral response to second harmonic generation and sum frequency generation (SFG) from a single molecular monolayer is often comparable with the achiral response. The chiral specificity also allows for symmetry-allowed SFG in isotropic chiral media, confirming predictions made approximately 50 years ago. With these experimental demonstrations in hand, an important challenge is the construction of intuitive predictive models that allow the measured chiral response to be meaningfully related back to molecular and macromolecular structure. This review defines and considers three distinct mechanisms for chiral effects in uniaxially oriented assemblies: orientational chirality, intrinsic chirality, and isotropic chirality. The role of each is discussed in experimental and computational studies of bacteriorhodopsin films, binaphthol, and collagen. Collectively, these three model systems support a remarkably simple framework for quantitatively recovering the measured chiral-specific activity.


Nonorganic failure to thrive in infancy: an update on nutrition, behavior, and growth.
Failure to thrive (FTT) has been defined in a number of ways, but most definitions include a weight less than the 5th percentile on the growth chart or a decreasing rate of weight gain. Nonorganic failure to thrive (NOFTT), i.e., FTT not due to organic disease, is the most common category of FTT in the United States and is associated with delayed growth and development and abnormal behaviors. Factors extrinsic to the infant are primarily responsible for NOFTT. That acute undernutrition may be a cause of the poor weight gain is suggested by anthropometric studies and by the observation that NOFTT infants often gain weight when food is supplied. Yet, decreased caloric intake has been documented in only a few infants, and not all infants immediately gain weight when given adequate calories. Current thinking attributes lack of weight gain in NOFTT to probably mixed interacting causes, including decreased nutrition, and abnormal hormonal mechanisms associated with abnormal behavior. That behavior and nutrition are related is recognized, but their interactions have not been adequately documented or explained. It is unknown whether behavior affects growth directly through nutrition or independently of nutrition. Until the cause or causes of poor growth and development in NOFTT are understood, permanently reversing the process will be difficult. This report reviews what is presently known about nutrition and growth in NOFTT.


The Role of SATB2 as a Diagnostic Marker of Sinonasal Intestinal-type Adenocarcinoma.
Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses is an uncommon tumor associated with exposure to wood and leather dust, nickel, and possibly smoking. ITAC shares phenotypical features with colorectal carcinoma. In contrast to most non-intestinal-type sinonasal adenocarcinomas, ITAC is an aggressive adenocarcinoma with poor clinical outcome; therefore, its reliable separation from non-ITAC is very important. The use of a combination of immunohistochemical markers of intestinal differentiation was tested in a cohort of sinonasal carcinomas of different types. The aim of this study was to explore a new intestinal marker, SATB2, in conjunction with CDX2 and CK20 in differential diagnosis of sinonasal adenocarcinomas. Seven ITACs, 66 non-ITACs, and 1 case of extensive intestinal metaplasia (IM) of the nasal mucosa were included in the study and stained with SATB2, CK20, CDX2, and CK7 antibodies. Detection of mismatch repair proteins was performed in all cases of ITAC. All 7 sinonasal ITACs have been tested for KRAS, NRAS, and BRAF gene mutations. All ITACs showed positive expression for SATB2, whereas all non-ITAC cases were negative. The only 1 case of IM was found to be positive for SATB2, whereas the same case showed negative expression of CK20 and only focal immunostaining for CDX2. The genetic analysis showed that only 1 sinonasal ITAC (1/7) showed KRAS c.35G>C, p.(Gly12Ala) mutation, whereas BRAF and NRAS genes were wild type. Four ITACs revealed wild-type KRAS, NRAS, and BRAF, and 2 remaining cases were not analyzable. All ITACs showed preserved nuclear expression of mismatch repair proteins. SATB2 in combination with CDX2 and CK20 differentiates sinonasal ITAC from non-ITAC with increased diagnostic sensitivity and specificity and detects IM in the sinonasal tract more easily.


Public Understanding and Attitudes towards Meat Chicken Production and Relations to Consumption.
Little is known about public knowledge of meat chicken production and how it influences attitudes to birds' welfare and consumer behaviour. We interviewed 506 members of the public in SE Queensland; Australia; to determine how knowledge of meat chicken production and slaughter links to attitudes and consumption. Knowledge was assessed from 15 questions and low scores were supported by respondents' self-assessed report of low knowledge levels and agreement that their knowledge was insufficient to form an opinion about which chicken products to purchase. Older respondents and single people without children were most knowledgeable. There was uncertainty about whether chicken welfare was adequate, particularly in those with little knowledge. There was also evidence that a lack of empathy towards chickens related to lack of knowledge, since those that thought it acceptable that some birds are inadequately stunned at slaughter had low knowledge scores. More knowledgeable respondents ate chicken more frequently and were less likely to buy products with accredited labelling. Approximately half of the respondents thought the welfare of the chicken was more important than the cost. It is concluded that the public's knowledge has an important connection to their attitudes and consumption of chicken.


Assistive devices caregivers use and find helpful to manage problem behaviors of dementia.
Use of assistive devices in caring for individuals with dementia has not been systematically examined, particularly as it concerns managing behavioral symptoms. We tested a nonpharmacologic intervention to manage behaviors that involved instructing families in effective communication techniques, simplifying tasks and the home environment and using assistive devices. This paper describes the assistive devices provided to families assigned to intervention, extent of use of issued devices, their perceived helpfulness, and cost. Following each treatment session, occupational therapists (OT) documented time spent training in the use of strategies to manage problem behaviors. For families receiving assistive devices, OTs asked caregivers after 4 months whether they continued to use the device (yes/no), and extent to which it helped manage the targeted problems (not at all, somewhat, very helpful). We also tracked the costs associated with ordering, delivering and installing devices. Of 272 caregiver-patient dyads enrolled in the original trial, 136 were randomized to the intervention group, of whom 63 received one or more assistive devices. Of 13 intervention sessions, an average of 4 (31%) involved discussing or training caregivers in using assistive devices. A total of 197 devices (3 per dyad) were issued of which 87.6% were reported in use at 4 months. Caregivers reported that overall, devices were somewhat to very helpful. Devices ranged in cost from US$4.80 to US$282.93 with an average cost per dyad of US$152.52(SD=US$102.70) which included the device, its ordering, delivery and installation.


An innovative approach to the recovery of phenolic compounds and volatile terpenes from the same fresh foliar sample of Rosmarinus officinalis L.
Rosmarinus officinalis L. is a plant of relevant commercial interest because of its volatile fraction and also its phenolic constituents which are both well known for their numerous properties. Nevertheless, an extractive method suitable to recovering both the aromatic and phenolic fractions from the same fresh foliar tissue has not yet been reported. In this work we have optimized a two-step procedure able to recover first the phenolic compounds and successively the volatile terpenes from the same foliar sample. The recovery of the whole phenolic fraction, partially degraded using a traditional extractive method, was guaranteed and we observed a significant increment in the amount of volatile terpenes compared to a traditional extraction procedure. We also highlight crucial information on the enzymatic activity of the endogenous oxidases that rapidly transform the phenolic substrates, mainly the rosmarinic acid. Our results suggest that this extractive procedure could also be used for other aromatic plants, thus providing a useful tool for more complete analyses of the main phytochemicals available in fresh foliar samples and creating the possibility of incrementing yields of volatile compounds.


Stimulus generalization and return of fear in C57BL/6J mice.
Return of fear following successful exposure therapy is a common problem. More insight into the characteristics of extinction learning is crucial in enhancing the efficiency of therapeutic interventions. In particular, understanding the mechanisms that underlie the generalization of extinction learning to other discrete stimuli is indispensable. Presently, little is known about the molecular and genetic mechanisms underlying this phenomenon. In this study, we attempt to develop a new conditioning protocol to study return of fear, caused by a stimulus change after extinction, in the most commonly used mouse strain of behavioral genetics, C57BL/6J. Perceptual changes to an auditory fear conditioned stimulus led to return of fear after initially successful fear-reduction, relative to appropriate control treatment. We argue that this protocol will be a useful tool to unravel the neurobiological underpinnings that regulate generalization of extinction and return of fear. Key questions for future research include the identification of crucial brain structures, neurotransmitters and signaling pathways that underly this behavioral phenomenon. Arguably, such research will open up new perspectives for neurobiological therapy augmentation.


[Hereditary hyperferritinemia-cataract syndrome].
Symptom-free brother and sister of Italian descent (age: 31 and 28 years), under examination to exclude haemochromatosis, were found to have increased serum ferritin levels. Both had cataracts removed, as had their mother. Physical examination had been normal in both siblings. Serum ferritin levels were raised to 926 and 956 ng/ml, respectively, while blood and differential counts, blood sugar and serum iron levels, iron binding capacity and transaminases were within normal limits. Liver sonography was normal and biopsies excluded haemochromatosis in both cases. The serum ferritin levels were elevated in all family members who had a cataract. Family history, greatly elevated serum ferritin levels and cataracts established diagnoses of hereditary hyperferritinaemia-cataract syndrome. The autosomally inherited hyperferritinaemia-cataract syndrome is a new condition that should be included in the differential diagnosis of hereditary hyperferritinaemia. A single measurement of the serum ferritin level and ophthalmological examination are sufficient to make the diagnosis; liver biopsy is unnecessary and blood letting contraindicated, because it would quickly cause microcytic iron-deficiency anaemia.


Glutamine deamidation: differentiation of glutamic acid and gamma-glutamic acid in peptides by electron capture dissociation.
Due to its much slower deamidation rate compared to that of asparagine (Asn), studies on glutamine (Gln) deamidation have been scarce, especially on the differentiation of its isomeric deamidation products: alpha- and gamma-glutamic acid (Glu). It has been shown previously that electron capture dissociation (ECD) can be used to generate diagnostic ions for the deamidation products of Asn: aspartic acid (Asp) and isoaspartic acid (isoAsp). The current study explores the possibility of an extension of this ECD based method to the differentiation of the alpha- and gamma-Glu residues, using three human Crystallin peptides (alphaA (1-11), betaB2 (4-14), and gammaS (52-71)) and their potentially deamidated forms as model peptides. It was found that the z(*)-72 ions can be used to both identify the existence and locate the position of the gamma-Glu residues. When the peptide contains a charge carrier near its N-terminus, the c+57 and c+59 ions may also be generated at the gamma-Glu residue. It was unclear whether formation of these N-terminal diagnostic ions is specific to the Pro-gamma-Glu sequence. Unlike the Asp containing peptides, the Glu containing peptides generally do not produce diagnostic side chain loss ions, due to the instability of the resulting radical. The presence of Glu residue(s) may be inferred from the observation of a series of z(n)(*)-59 ions, although it was neither site specific nor without interference from the gamma-Glu residues. Finally, several interference peaks exist in the ECD spectra, which highlights the importance of the use of high performance mass spectrometers for confident identification of gamma-Glu residues.


Metabolic profiling of different wild and cultivated Allium species based on high-resolution mass spectrometry, high-performance liquid chromatography-photodiode array detector, and color analysis.
Many plants of the genus Allium are widely cultivated and consumed for their nutraceutical and health-enhancing bioactive components effective in many metabolic and infectious diseases. In particular, Allium sativum L. (garlic), the most economically important Allium species, is known to present volatile, comparatively polar sulfur-containing compounds responsible for both the typical garlic aroma and antimicrobial property. More recently, the (moderately) polar portion of garlic metabolome, rich of polyphenols and amino acids, is gaining increasing interest as a source of antioxidants and primary nutrients. In this study, we have explored the chemical diversity of eight different hydroalcoholic extracts obtained by microwave-assisted extraction of white and red crop A. sativum and wild Allium triquetrum, Allium roseum, and Allium ampeloprasum, all originating from the Mediterranean Basin. The aim is to appraise their potential dietetic and healing value through an in-depth chemical characterization and contribute to preserve and exploit natural resources. The multimethodological method applied here is based on an untargeted metabolic profiling by means of high-resolution electrospray ionization Fourier-transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry. More than 850 by ESI(+) and 450 by ESI(-) putative metabolites have been annotated covering all main classes of primary and secondary metabolites, including amino acids, alkaloids, organic and fatty acids, nucleotides, vitamins, organosulfur compounds, and flavonoids. The pigment and polyphenol components have been separated and quantified by a targeted chromatographic high-performance liquid chromatography-photodiode array detector (HPLC-PDA) and CIEL*a*b* colorimetric assay, showing characteristic yellow and red components in each extract, related to a different milieu of anthocyanins and flavonoids as assigned by high-resolution mass spectrometry (MS).


Complications of transvaginal silicone-coated polyester synthetic mesh sling.
To report a premarket multicenter trial to test the feasibility of a transvaginal silicone-coated polyester synthetic mesh sling in women with anatomic incontinence. Fifty-one patients in four centers underwent transvaginal placement of a silicone-coated polyester synthetic mesh sling (American Medical Systems) during an 8-month period. Of the 51 patients, 31 were part of a prospective institutional review board-approved feasibility trial in three centers funded by American Medical Systems (group 1) and 20 underwent implantation by a single surgeon and their data were retrospectively reviewed (group 2). The studies were done concomitantly, and all slings were fixed transvaginally with bone anchors. All patients in group 1 were followed up at 4 weeks, 6 months, and 1 year (as applicable) with repeat questionnaires, physical examinations, and pad tests. In group 1, 20 patients completed 6 months of follow-up. Ten patients (32%) required a second surgical procedure at an average of 183 days (range 68 to 343) postoperatively. Eight patients (26%) had vaginal extrusion of the mesh, one (3%) required sling lysis, and one (3%) required sling removal because of infection. In group 2, 8 patients (40%) underwent sling removal for vaginal extrusion at a mean of 160 days (range 83 to 214). Transvaginally placed silicone-coated mesh slings used for the treatment of urinary incontinence demonstrated an unacceptably high vaginal extrusion rate in this study. Once identified, this study was immediately terminated, and this product was not marketed for this application in the United States.


A transgenic mouse model of hemoglobin S Antilles disease.
Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human Hb but causes a more severe phenotype than Hb S. Two homozygous viable Hb S Antilles transgene insertions from Tg58Ru and Tg98Ru mice were bred into MHOAH mice that express high oxygen affinity (P50 approximately 24.5 mm Hg) rather than normal (P50 approximately 40 mm Hg) mouse Hbs. The rationale was that the high oxygen affinity MHOAH Hb, the lower oxygen affinity of Hb S Antilles than Hb S (P50 approximately 40 v 26.5 mm Hg), and the lower solubility of deoxygenated Hb S Antilles than Hb S (approximately 11 v 18 g/dL) would favor deoxygenation and polymerization of human Hb S Antilles in MHOAH mouse red blood cells (RBCs). The Tg58 x Tg98 mice produced have a high and balanced expression (approximately 50% each) of h alpha and h beta(S Antilles) globins, 25% to 35% of their RBCs are misshapen in vivo, and in vitro deoxygenation of their blood induces 30% to 50% of the RBCs to form classical looking, elongated sickle cells with pointed ends. Tg58 x Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.


Protein-protein interaction detection in vitro and in cells by proximity biotinylation.
We report a new method for detection of protein-protein interactions in vitro and in cells. One protein partner is fused to Escherichia coli biotin ligase (BirA), while the other protein partner is fused to BirA's "acceptor peptide" (AP) substrate. If the two proteins interact, BirA will catalyze site-specific biotinylation of AP, which can be detected by streptavidin staining. To minimize nonspecific signals, we engineered the AP sequence to reduce its intrinsic affinity for BirA. The rapamycin-controlled interaction between FKBP and FRB proteins could be detected in vitro and in cells with a signal to background ratio as high as 28. We also extended the method to imaging of the phosphorylation-dependent interaction between Cdc25C phosphatase and 14-3-3epsilon phosphoserine/threonine binding protein. Protein-protein interaction detection by proximity biotinylation has the advantages of low background, high sensitivity, small AP tag size, and good spatial resolution in cells.


Early chest tube removal after video-assisted thoracic surgery lobectomy with serous fluid production up to 500 ml/day.
In fast-track pulmonary resections, we removed chest tubes after video-assisted thoracic surgery (VATS) lobectomy with serous fluid production up to 500 ml/day. Subsequently, we evaluated the frequency of recurrent pleural effusions requiring reintervention. Data from 622 consecutive patients undergoing VATS lobectomy from January 2009 to December 2011 were registered prospectively in an institutional database. Data included age, gender, lobe(s) resected, bleeding and duration of surgery. Follow-up was 30 days from discharge. All complications requiring pleurocentesis or reinsertion of a chest tube, and all readmissions were registered. Twenty-three patients were excluded due to missing data, in-hospital mortality and loss to follow-up, leaving 599 for final analysis. Our primary outcome was the number of patients requiring reintervention due to recurrent pleural effusion. Secondary outcomes included time of chest tube removal and time to discharge. The incidence of recurrent pleural effusions requiring reintervention was compared between three groups according to the postoperative day (POD) of chest tube removal (Day 0-1, 2-3 and ≥4, respectively) using Fisher's exact test. Pleural effusion after chest tube removal required reintervention in 17 patients (2.8%). Of these, 7 needed readmission. Median time from surgery to chest tube removal was 2 days, and median time from surgery to discharge was 4 days. No statistically significant association was found between the incidence of reinterventions due to recurrent pleural effusion and the POD of chest tube removal (P=0.50). The median time from chest tube removal to discharge was 1 day in all groups. Of the patients who needed reintervention, none had complications regarding this, except one who developed pneumothorax after pleurocentesis. Our findings suggest that chest tube removal after VATS lobectomy is safe despite volumes of serous fluid production up to 500 ml/day. The proportion of patients who developed pleural effusion necessitating reintervention was low (2.8%), and a complication of the reintervention was seen in only 1 patient.


The Application of the Rare Earths to Magnesium and Titanium Metallurgy in Australia.
Rare earth elements (REEs) have found application in metallurgical processes for nearly a century due to their unique chemical and physical properties but have gained increased attention in recent decades. Notably, the use of these elements may assist in the development of advanced magnesium and titanium products for applications spanning biomedicine, aerospace, and the automotive industry. To this end, current progress in this area, highlighting work done in Australian research organizations with particular academic expertise, is reviewed. Two areas that require further research are identified: the application of Sc and the heavy lanthanides to the development of novel magnesium alloys and the use of REEs as additives in the development of additive manufacturing of titanium parts.


Use of Fluoroscopy and Potential Long-Term Radiation Effects on Cataract Formation.
The lens of the eye is extremely susceptible to radiation and long-term exposure can induce cataract formation. Our objective was to explore the risk of cataract formation for urologists at our institution. A retrospective review of a multisurgeon database of fluoroscopic cases between October 2013 to December 2014 was queried. Procedures were performed by different subspecialties and ranged from stent insertion/ureteroscopy to percutaneous nephrolithotomy. Fluoroscopic parameters were recorded from all cases and the radiation dosimetry was calculated through methods described by the National Council on Radiation Protection. The data were extrapolated to determine the risk of cataract formation. The technical specifications of the GE OEC 990 mobile C-arm unit were used for calculations. A total of 780 cases were analyzed, of which 182 were endourology cases. Average fluoroscopic time was 34.86 seconds per case. Average tube potential and current were 86.84 kV and 1.95 mA, respectively. Pediatric urologists utilized fluoroscopy the least, 11.84 seconds per case (p = 0.0022). Endourology trained faculty had fluoroscopy exposure of 68.35 seconds per case (p < 0.0001), whereas others were exposed 26.24 seconds per case (p < 0.0001). For the highest exposed urologist, the estimated dose to the eyes was 5.64 μGy per case. Total estimated cumulative dose over the study timeframe was 997.58 μGy, or 748.19 μGy per year. The defined threshold in the absorbed dose for cataract formation is 0.5 Gy. Resident exposure was the highest, at 11% of the annual limit, and the most exposed urologists had an estimated dose of 5% of the annual limit. At current exposure levels, it would not be feasible to reach the stated safety limit during 50 to 60 years of practice. However, changing exposure guidelines could result in stricter safety limits.


Marine anti-biofouling efficacy of amphiphilic poly(coacrylate) grafted PDMSe: effect of graft molecular weight.
There is currently strong motivation due to ecological concerns to develop effective anti-biofouling coatings that are environmentally benign, durable, and stable for use by the maritime industry. The antifouling (AF) and fouling-release (FR) efficacy of amphiphilic, charged copolymers composed of ~52% acrylamide, ~34% acrylic acid, and ~14% methyl acrylate grafted to poly(dimethyl siloxane) (PDMSe) surfaces were tested against zoospores of the green alga Ulva linza and the diatom Navicula incerta. The biofouling response to molecular weight variation was analyzed for grafts ranging from ~100 to 1,400 kg mol-1, The amphiphilic coatings showed a marked improvement in the FR response, with a 55% increase in the percentage removal of diatoms and increased AF efficacy, with 92% reduction in initial attachment density of zoospores, compared to PDMSe controls. However, graft molecular weight, in the range tested, was statistically insignificant. Grafting copolymers to PDMSe embossed with the Sharklet™ microtopography did not produce enhanced AF efficacy.


Hypoperfusion intensity ratio as a predictor of outcomes after thrombectomy triage: A call for data homogeneity.
Collateral blood flow markers have been associated with outcomes after thrombectomy in patients presenting with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Hypoperfusion intensity ratio (HIR), a metric reflecting tissue level collaterals, is one such marker with the potential to delineate patients who do and do not do well after thrombectomy. We determined if HIR correlated with successful reperfusion after thrombectomy. Using Nested Knowledge, we screened literature for studies comparing patients with favorable versus unfavorable HIR, distinguished by a cutoff of 0.4, who underwent thrombectomy triage. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction ≥2b and secondary outcomes included rate of symptomatic intracranial hemorrhage, mortality at 90 days, and modified Rankin scale scores 0-2 at 90 days. A random effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Three studies with 973 patients, 496 with favorable HIR, and 477 with unfavorable HIR were included in this meta-analysis. The odds of reperfusion success were not significantly different between patients who had favorable versus unfavorable HIR (OR 0.96, 95% CI: 0.31-3.04) across two of the studies. Analysis of the remaining outcome variables was precluded by significant heterogeneity in data element reporting. This meta-analysis was considerably limited by heterogeneity. Future meta-analyses on this topic, and other topics in the field of neurointervention would benefit from improved harmonization of study design and data element reporting.


Positive Feelings After Casual Sex: The Role of Gender and Traditional Gender-Role Beliefs.
The purpose of this study was to identify predictors of positive and negative affect following casual sex. Specifically, the primary goal was to investigate how traditional gender-role beliefs, peer approval of casual sex, perceptions of others, sexual assertiveness, and sexual pleasure influence affective experiences. Second, we aimed to determine the extent to which these associations were comparable for men and women. Although we expected mean differences on many of these constructs (e.g., men perceiving more peer approval), we expected the relationships between these constructs to be comparable for women and men. Participants ages 18 to 35 (N = 585) were recruited from a large university and Amazon Mechanical Turk (MTurk) and described their most recent casual sex experience in a self-report questionnaire. Structural equation modeling (SEM) analyses indicated that gender-role beliefs were significantly associated with less sexual assertiveness and more negative perceptions of others; for women they were also associated with less peer approval of casual sex. For women and men, sexual assertiveness predicted sexual pleasure; and sexual pleasure was associated with affect. To decrease the gender discrepancy in positive affect and sexual pleasure, it is important to develop a comprehensive understanding of the interrelationships among norms, casual sex experiences, and affect.


Vascular arrangement in the skin of tropical cattle.
The vascular arrangement in the skin of some tropical breeds of cattle and of temperate cattle in a tropical environment is reported. Four vascular plexuses were observed in the skin of all breeds of cattle studied. The first horizontal plexus was observed between the subcutaneous and reticular layers, the second at mid-reticular layer level, and the third and most prominent at the level of the hair papillae and sweat glands. The fourth plexus arose as a branch from the third, extended upwards to the sebaceous gland and upper hair follicle region and gave off twigs to the dermo-epidermal junction. The sweat glands and hair follicles were profusely supplied with blood vessels. The branches of the fourth plexus extended closer to the epidermis in the tropical breeds than in the Friesian.


Revising recognition judgments during noisy recognition evidence accumulation: The dynamics of losses versus gains.
Outside the laboratory, we sometimes revise our recognition judgments of others-realizing, for example, that we have accidentally failed to greet an acquaintance we just passed in the hallway. These recognition reversals have rarely been studied. Here, using a basic noisy-accumulation framework, we simulated recognition response reversals in which initial speeded recognition judgments were followed by an opportunity to revise the initial judgment. The simulation predictions were compared to empirical data from two experiments in which we gave participants the opportunity to revise each of their initial speeded recognition judgments. The speeded old-new responses were restricted to either 300-800 ms (Exp. 1) or 200-600 ms (Exp. 2) after each probe's onset, and the second response was self-paced in both experiments. The noisy-accumulation framework correctly anticipated three findings. First, gain rates (incorrect followed by correct responses) always exceeded loss rates (correct followed by incorrect responses). Second, despite being corrective, the raw gain rates exhibited a modest negative correlation with overall recognition skill. Third, when gain rates were conditioned on the opportunity to correct an initial error (conditional gain rate), they were then positively correlated with recognition skill but were less diagnostic than the conditional loss rates. Thus, the mechanics of noisy accumulation naturally predict that skilled recognizers will demonstrate infrequent corrective behavior but a high probability of correction, should an initial error occur.


Benzoxazole-based heterometallic dodecanuclear complex [Dy(III)4Cu(II)8] with single-molecule-magnet behavior.
Three Cu-Ln (Ln = Dy, Gd, Y) dodecanuclear clusters assembled by a novel ligand of the benzoxazole type are reported. The dysprosium cluster exhibits a frequency dependence of the alternating-current susceptibility and hysteresis loop at low temperature, indicating single-molecule-magnet behavior.


Incidence trends and risk factors of lung cancer in never smokers: Pooled analyses of seven cohorts.
The trends in incidence of lung cancer in never smokers are unclear as well as the significance of risk factors. We studied time trends in the incidence and risk factors of lung cancer in never smokers in Finland in a large, pooled cohort. We pooled data from seven Finnish health cohorts from the period between 1972 and 2015 with 106 193 never smokers. The harmonised risk factors included education, alcohol consumption, physical activity, height and BMI. We retrieved incident lung cancers from the nation-wide Finnish Cancer Registry. We estimated average annual percent change (AAPC) and the effects of risk factors on cause-specific hazard ratios (HRs) of lung cancer using Poisson regression. We detected 47 lung cancers in never smoking men (n = 31 859) and 155 in never smoking women (n = 74 334). The AAPC of lung cancer incidence was -3.30% (95% confidence interval [CI]: -5.68% to -0.88%, P = .009) in never smoking men and 0.00% (95% CI: -1.57% to 1.60%, P = .996) in never smoking women. Of the five studied risk factors only greater height in women had a statistically significant increased risk of lung cancer (multivariate HR = 1.84, 95%CI: 1.08 to 3.12). It is plausible that tobacco control measures focused on working places have reduced passive smoking among men more than among women, which could explain the declining trend in lung cancer incidence in never smoker men but not in never smoker women. As tobacco control measures have not been targeted to domestic environments, it is likely that women's exposure to passive smoking has continued longer.


Mimicking enzymatic transaminations: attempts to understand and develop a catalytic asymmetric approach to chiral alpha-amino acids.
Attempts are made to build a bridge between asymmetric catalysis and enzymatic reactions by mechanistic investigations and the development of a catalytic and enantioselective approach to amination of alpha-keto esters by primary amines catalyzed by chiral Lewis acids as a model for transamination enzymes. Different Lewis acids can catalyze the half-transamination of alpha-keto esters using primary amine nitrogen sources such as pyridoxamine and 4-picolylamine. The mechanistic studies of the Lewis-acid catalyzed half-transamination using deuterium-labelled compounds show the incorporation of deuterium atoms in several positions of the alpha-amino acid derivative, indicating that the enol of the alpha-keto ester plays an important role along the reaction path. The catalytic enantioselective reactions are dependent on the pKa-value of the solvent since enantioselectivities were only obtained in solvents with high pKa-values relative to methanol. However, stronger acidic conditions generally gave better yields, but poor enantioselectivities. A series of chiral Lewis acids were screened as catalysts for the enantioselective half-transamination reactions and moderate yields and enantioselectivities of up to 46% ee were obtained.


Future diagnostic agents.
Timely and specific diagnosis of infectious diseases can be clinically challenging but essential for the patient's outcome. Laboratory tests, such as a blood culture or urine specimen, can detect the responsible micro-organism but cannot discriminate between sterile inflammatory disease and truly infectious disease. Imaging tests, like scintigraphic techniques, can pinpoint the infection in the body. There are a number of clinical scintigraphic tests from which to choose, and no single test is optimal for the various presentations of clinical infectious disease. The currently available radiopharmaceuticals often are not capable of distinguishing between sterile inflammation, and bacterial or fungal infections. Neutrophil-mediated processes, characteristic for both inflammatory and infectious processes, can be targeted in situ by radiolabeled leukocytes, antibodies or fragments, or even by cytokines and (18)F-fluorodeoxyglucose. Unfortunately those techniques are not infection-specific markers, and ongoing research is in progress to tackle this problem. The most promising option in this respect is directly targeting bacteria or fungi with radiolabeled antibiotics or antimicrobial peptides. These theoretically highly infection-specific radiopharmaceuticals could be used for monitoring the success of antimicrobial therapy of infectious disease. Although results from preclinical experiments and pilot studies in patients are promising, radiolabeled anti-infective agents are not currently in routine clinical use and studies are continuing to prove their effectiveness for diagnostic imaging of infections in the future.


Characterization of murine monoclonal antibodies against Helicobacter pylori lipopolysaccharide specific for Lex and Ley blood group determinants.
The cell envelope of Helicobacter pylori contains lipopolysaccharide (LPS), the O-chain of which expresses type 2 Lex and Ley blood group antigens, which mimic human gastric mucosal cell-surface glycoconjugates and may contribute to the survival of H. pylori in gastric mucosa. Here we describe the generation of monoclonal antibodies specific for Lex and Ley blood group determinants and the characterization of their binding properties using purified, structurally defined H. pylori LPS, synthetic glycoconjugates, and H. pylori cells. Analysis of oligosaccharide binding by SPR provided a rapid and reliable means for characterization of antibody affinities. One of the antibodies, anti-Lex, was of IgG3 subclass and had superior binding characteristics as compared with the commercially available anti-Lex IgM. These antibodies could have potential in the immunodiagnosis of certain types of cancer, in serotyping of H. pylori isolates, and in structure-function studies.


Nonradiative decay dynamics of methyl-4-hydroxycinnamate and its hydrated complex revealed by picosecond pump-probe spectroscopy.
The lifetimes of methyl 4-hydroxycinnamate (OMpCA) and its mono-hydrated complex (OMpCA-H(2)O) in the S(1) state have been measured by picosecond pump-probe spectroscopy in a supersonic beam. For OMpCA, the lifetime of the S(1)-S(0) origin is 8-9 ps. On the other hand, the lifetime of the OMpCA-H(2)O complex at the origin is 930 ps, which is ∼100 times longer than that of OMpCA. Furthermore, in the complex the S(1) lifetime shows rapid decrease at an energy of ∼200 cm(-1) above the origin and finally becomes as short as 9 ps at ∼500 cm(-1). Theoretical calculations with a symmetry-adapted cluster-configuration interaction (SAC-CI) method suggest that the observed lifetime behavior of the two species is described by nonradiative decay dynamics involving trans → cis isomerization. That is both OMpCA and OMpCA-H(2)O in the S(1) state decay due to the trans → cis isomerization, and the large difference of the lifetimes between them is due to the difference of the isomerization potential energy curve. In OMpCA, the trans → cis isomerization occurs smoothly without a barrier on the S(1) surface, while in the OMpCA-H(2)O complex, there exists a barrier along the isomerization coordinate. The calculated barrier height of OMpCA-H(2)O is in good agreement with that observed experimentally.


Proposal to modify the Note to Rule 61 of the International Code of Nomenclature of Prokaryotes.
In view of the current difficulty to make minor typographical or orthographic corrections to incorrectly formed names of taxa, we propose a change in the text of the Note to Rule 61 of the International Code of Nomenclature of Prokaryotes, to be applied retroactively from August 2009. The proposed change will enable the List Editors of the International Journal of Systematic and Evolutionary Microbiology and others to correct minor errors without having to refer each case to the Judicial Commission of the International Committee for Systematics of Prokaryotes.


[Disturbances in volume and electrolytes with intestinal and kidney diseases].
The intestines and kidney are the most important excretion organs. Both organ systems are key players in keeping the homeostatic balance regarding hydration and electrolytes. Disturbances of function can lead to enormous and sometimes life-threatening complications. Intestinal diseases lead often to diarrhoea, which can be associated with fluid loss of up to 20 l per day. The accompanying electrolyte disturbances can be hypo- or hypernatremia in combination with hypokalemia. The therapy is substitution guided by knowledge of the pathophysiology. Kidney diseases lead to excessive volume and electrolyte balances, depending on the underlying molecular or pathological defect, but deficiencies can also be found. In case of kidney impairment with 30-50% total loss of function, calcium and phosphate metabolism is impaired.


Abietane Diterpenoids with Antioxidative Damage Activity from Rosmarinus officinalis.
Nine new and nineteen known compounds were isolated and identified from Rosmarinus officinalis under the guidance of bioassay and LCMS. They all belonged to abietane diterpenoids which enriched the types of compounds in R. officinalis, especially the discovery of a series of 20-norabietane diterpenoids (4, 6-9, and 26-27). The antioxidative damage activity of the compounds was tested on H2O2 damaged SH-SY5Y cells. Compounds 5, 6, and 7 presented moderate ability for promoting the growth of damaged cells. Compounds 10, 11, 13-20, 27, and 28 displayed a high antioxidative damage effect whose cell viability rates were more than 80%. The antioxidative damage effect of 11, 16, 18, and 20 were higher than that of EGCG (positive control) in which 11, 18, and 20 were the acetylated derivatives of carnosic acid (10), 7α-methoxy-isocarnosol (16), and carnosol (19), respectively. It suggested that 10-carboxyl/formyl of abietane diterpenoids was essential for maintaining the antioxidative damage activity and the adjacent hydroxyl groups on the benzene ring was less important for holding the bioactivity. These acetylated derivatives with high bioactivity and stability could be regarded as new sources of antioxidants or antioxidative damage agents being used in the food and medical industry.


Spouses in mixed-orientation marriage: a 20-year review of empirical studies.
Empirical studies on mixed-orientation marriage in social science journals from 1988 to 2008 were reviewed. Fifteen articles published in eight peer-reviewed journals were identified and discussed in terms of sampling, design, measures, rigor, theoretical framework, and literature review. An overview of each study is provided along with a summary of critical findings. Implications and recommendations for future research and education are offered.


Prevalence of M75 Streptococcus pyogenes Strains Harboring slaA Gene in Patients Affected by Pediatric Obstructive Sleep Apnea Syndrome in Central Italy.
Recently we reported an association between pediatric obstructive sleep apnea syndrome (OSAS) and Group A streptococcus (GAS) sub-acute chronic tonsil colonization. We showed that GAS may contribute to tonsil hyperplasia via a streptolysin O (SLO)-dependent cysteinyl leukotrienes (CysLTs) production, which can trigger T and B cell proliferation. In the present study, we characterized the GAS strains isolated from pediatric OSAS patients in comparison with a panel of age and sex matched GAS strains unrelated to OSAS, but isolated in the same area and during the same period ranging from 2009 to 2013. We found that slaA gene, previously reported to be associated to CysLTs production pathway, was significantly associated to GAS OSAS strains. Moreover, the most numerous group (32%) of the GAS OSAS strains belonged to M75 type, and 6 out of 7 of these strains harbored the slaA gene. Multilocus Sequence Typing (MLST) experiments demonstrated that the clone emm75/ST49/ smeZ, slaA was associated to OSAS cases. In conclusion, we found an association between slaA gene and the GAS OSAS strains, and we showed that the clone emm75/ST49 harboring genes smeZ and slaA was exclusively isolated from patients affected by OSAS, thus suggesting that this genotype might be associated to the pathogenesis of OSAS, although further studies are needed to elucidate the possible role of SlaA in tonsil hypertrophy development.


Effect of compressive force on the production of prostaglandin E(2) and its receptors in osteoblastic Saos-2 cells.
In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We examined the effect of compressive force (CF) on PGE(2) production, PGE receptors (Ep1-4) expression, phosphorylation of protein kinase A (p-PKA), and calcium content in Saos-2 cells. PGE(2) production increased as CF strength. Applying CF of 98 or 294 Pa caused the cells to produce approximately 700 and 1,400 pg/mL PGE(2), respectively. CF of 98 Pa increased Ep2 gene expression, and 98 and 294 Pa CF increased Ep4. Immunohistochemical staining showed strong expression of Ep2 under 98 Pa and Ep4 under 98 and 294 Pa. The p-PKA increased as the strength of CF or PGE(2) concentration. The calcium content was increased by the addition of 700 pg/mL PGE(2) but was decreased by 1400 pg/mL. Thus, mechanical stress controls bone formation by stimulating PGE(2) production and Ep2 and/or Ep4 expression in osteoblasts.


FOXO transcription factors protect against the diet-induced fatty liver disease.
Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls. However, the HFC diet led to more severe liver injury and fibrosis compared to the HFD diet. At the molecular levels, hepatic Foxo1/3/4 deficiency triggered a significant increase in the expression of inflammatory and fibrotic genes including Emr1, Ccl2, Col1a1, Tgfb, Pdgfrb, and Timp1. Thus, our data suggest that FOXO transcription factors play a salutary role in the protection against the diet-induced fatty liver disease.


Biochemical conservation and evolution of germacrene A oxidase in asteraceae.
Sesquiterpene lactones are characteristic natural products in Asteraceae, which constitutes approximately 8% of all plant species. Despite their physiological and pharmaceutical importance, the biochemistry and evolution of sesquiterpene lactones remain unexplored. Here we show that germacrene A oxidase (GAO), evolutionarily conserved in all major subfamilies of Asteraceae, catalyzes three consecutive oxidations of germacrene A to yield germacrene A acid. Furthermore, it is also capable of oxidizing non-natural substrate amorphadiene. Co-expression of lettuce GAO with germacrene synthase in engineered yeast synthesized aberrant products, costic acids and ilicic acid, in an acidic condition. However, cultivation in a neutral condition allowed the de novo synthesis of a single novel compound that was identified as germacrene A acid by gas and liquid chromatography and NMR analyses. To trace the evolutionary lineage of GAO in Asteraceae, homologous genes were further isolated from the representative species of three major subfamilies of Asteraceae (sunflower, chicory, and costus from Asteroideae, Cichorioideae, and Carduoideae, respectively) and also from the phylogenetically basal species, Barnadesia spinosa, from Barnadesioideae. The recombinant GAOs from these genes clearly showed germacrene A oxidase activities, suggesting that GAO activity is widely conserved in Asteraceae including the basal lineage. All GAOs could catalyze the three-step oxidation of non-natural substrate amorphadiene to artemisinic acid, whereas amorphadiene oxidase diverged from GAO displayed negligible activity for germacrene A oxidation. The observed amorphadiene oxidase activity in GAOs suggests that the catalytic plasticity is embedded in ancestral GAO enzymes that may contribute to the chemical and catalytic diversity in nature.


Mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymers.
Majority of infectious microorganism make their gateway to the host through mucosal surfaces, such as gastrointestinal tract, nasal and vaginal tract. Mucosal immune response structured as sIgA can effectively prevent the attachment and invasion of the microorganism from mucosal surface and thereby serves as an efficient tool against infectious disease. There has been an increased demand for the development of novel vaccine that leads to the induction of immune response in systemic circulation as well as at mucosal surfaces against infectious disease. Mucosal delivery of vaccine provides basis for induction of both mucosal as well as systemic immune responses against the infectious organisms. However, a variety of factors such as mucociliary clearance, presence of deteriorating enzymes, pH extremes (GIT), low permeation and metabolic degradation limit the mucosal delivery of vaccine. Numerous strategies have been explored in the meadow of mucosal vaccination for the purpose of efficient antigen delivery through mucosal route(s). Polymeric carrier(s) such as nanoparticles and microparticles loaded with the antigen can serve as the basis for creation of important formulations for improved vaccine. Biodegradable and mucoadhesive polymeric carrier(s) seems to be most promising candidate for mucosal vaccine delivery. Several polymers from natural and synthetic origin, such as polylactide-co-glycolide, chitosan, alginate, carbopol, gelatin etc., have been explored for the efficient mucosal vaccine delivery and significant results have been obtained. This review outlines the polymers used in mucosal vaccine delivery with special reference to mucoadhesive/biodegradable polymers. This article also covers the recent patent granted in the field on polymeric carrier mediated mucosal vaccination.


[Controversies and prospects for surgical treatment of pancreatic neuroendocrine neoplasms with liver metastases].
The incidence of pancreatic neuroendocrine neoplasm(pNEN) increased over the past two decades. Liver metastasis, the most common type of distal metastasis, is also one of the most important prognostic factors. Although several medical treatments, including biotherapy, chemotherapy, targeted therapy, peptide receptor radionuclide therapy and locoregional therapy, are available for pNEN with liver metastases, surgery is still the only possible treatment for cure. Currently, there are several controversies as regards surgical treatment for pNEN with liver metastases. These controversies include, but are not limited to, whether surgical resection is appropriate for pancreatic neuroendocrine tumor G3 with liver metastases, how to classify primary lesion and hepatic metastases comprehensively and accurately, what is the optimal surgical strategy for type Ⅱ liver metastases, who can benefit greatly from cytoreduction, and how to refine the Milan criteria for liver transplantation. This article aims to discuss those main controversies and provide prospects for future clinical trials.


Genetic genealogy comes of age: perspectives on the use of deep-rooted pedigrees in human population genetics.
In this article, we promote the implementation of extensive genealogical data in population genetic studies. Genealogical records can provide valuable information on the origin of DNA donors in a population genetic study, going beyond the commonly collected data such as residence, birthplace, language, and self-reported ethnicity. Recent studies demonstrated that extended genealogical data added to surname analysis can be crucial to detect signals of (past) population stratification and to interpret the population structure in a more objective manner. Moreover, when in-depth pedigree data are combined with haploid markers, it is even possible to disentangle signals of temporal differentiation within a population genetic structure during the last centuries. Obtaining genealogical data for all DNA donors in a population genetic study is a labor-intensive task but the vastly growing (genetic) genealogical databases, due to the broad interest of the public, are making this job more time-efficient if there is a guarantee for sufficient data quality. At the end, we discuss the advantages and pitfalls of using genealogy within sampling campaigns and we provide guidelines for future population genetic studies.