Global-, Regional-, and Country-Level Economic Impacts of Dental Diseases in 2015.
Up-to-date information about the economic impact of dental diseases is essential for health care decision makers when seeking to make rational use of available resources. The purpose of this study was to provide up-to-date estimates for dental expenditures (direct costs) and productivity losses (indirect costs) due to dental diseases on the global, regional, and country level. Direct costs of dental diseases were estimated using a previously established systematic approach; indirect costs were estimated using an approach developed by the World Health Organization Commission on Macroeconomics and Health and factoring in 2015 values for gross domestic product and disability-adjusted life years from the Global Burden of Disease Study. The estimated direct costs of dental diseases amounted to $356.80 billion and indirect costs were estimated at $187.61 billion, totaling worldwide costs due to dental diseases of $544.41 billion in 2015. After adjustment for purchasing power parity, the highest levels of per capita dental expenditures were found for High-Income North America, Australasia, Western Europe, High-Income Asia Pacific, and East Asia; the highest levels of per capita productivity losses were found for Western Europe, Australasia, High-Income North America, High-Income Asia Pacific, and Central Europe. Severe tooth loss was found to imply 67% of global productivity losses due to dental diseases, followed by severe periodontitis (21%) and untreated caries (12%). From an economic perspective, improvements in population oral health may be highly beneficial and could contribute to further increases in people's well-being given available resources.


Barriers, support, and resilience of prospective first-in-family university students: Australian high school educators' perspective.
First-in-family (FiF) university students-or first generation students-are recognised to have disadvantages and lack social and cultural capital compared with non-FiF students. The challenges FiF students encounter at university are well understood, however, their journey begins while still in high school. We call this high school cohort prospective FiF (PFiF) students and young people whose parents never attended university. This qualitative study explored the perspectives of 10 high school educators from Melbourne, Australia about the barriers and supports PFiF students encounter as they navigate the path to university. Participants identified that family inexperience, unsupportive attitudes at home and at school, lack of financial capacity and invisibility represented barriers. However, participants also explained that PFiF students can be resilient and motivated, especially when combined with appropriate support from schools, family, and university programmes. The findings highlight the challenges for PFiF and bring much-needed attention to their challenges and needs in the early transition to higher education.


Dry eye syndrome, posttraumatic stress disorder, and depression in an older male veteran population.
To evaluate whether veterans with posttraumatic stress disorder (PTSD) or depression have differences in dry eye symptoms and signs compared to a population without these conditions. Male patients aged ≥50 years with normal eyelid, conjunctival, and corneal anatomy were recruited from the Miami Veterans Affairs Eye Clinic (N = 248). We compared dry eye symptoms (determined by the Dry Eye Questionnaire 5 [DEQ5] score) to tear film indicators obtained by clinical examination (i.e., tear osmolarity, corneal staining, tear breakup time, Schirmer's, meibomian gland quality, orifice plugging, lid vascularity) between patients with PTSD or depression and those without these conditions. Student's t-tests, χ(2) analyses, and linear and logistic regressions were used to assess differences between the groups. DEQ5 scores were higher in the PTSD (mean = 13.4; standard error [SE] = 1.1; n = 22) and depression (mean = 12.0; SE = 0.8; n = 40) groups compared to the group without these conditions (mean = 9.8; SE = 0.4; n = 186; P < 0.01 and P = 0.02, respectively). More patients in the PTSD and depression groups had severe dry eye symptoms, defined as a DEQ5 score ≥ 12 (77% and 63% vs. 41%; P < 0.01 and P = 0.02, respectively). No significant differences in tear film indicators were found among the three groups. Multivariable logistic regression indicated that a PTSD diagnosis (odds ratio [OR] = 4.08; 95% confidence interval [CI] = 1.10-15.14) and use of selective serotonin reuptake inhibitors (OR = 2.66; 95% CI = 1.01-7.00) were significantly associated with severe symptoms. Patients with PTSD have ocular surface symptoms that are not solely explained by tear indicators. Identifying underlying conditions associated with ocular discomfort is essential to better understand the mechanisms behind ocular pain in dry eye syndrome.


Black Pod Syndrome of Lupinus angustifolius Is Caused by Late Infection with Bean yellow mosaic virus.
Black pod syndrome (BPS) causes devastating losses in Lupinus angustifolius (narrow-leafed lupin) crops in Australia, and infection with Bean yellow mosaic virus (BYMV) was suggested as a possible cause. In 2011, an end-of-growing-season survey in which L. angustifolius plants with BPS were collected from six locations in southwestern Australia was done. Tissue samples from different positions on each of these symptomatic plants were tested for BYMV and generic potyvirus by enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction (RT-PCR). Detection was most reliable when RT-PCR with generic potyvirus primers was used on tissue taken from the main stem of the plant just below the black pods. Partial coat protein nucleotide sequences from eight isolates from BPS-symptomatic L. angustifolius plants all belonged to the BYMV general phylogenetic group. An initial glasshouse experiment revealed that mechanical inoculation of L. angustifolius plants with BYMV after pods had formed caused pods to turn black. This did not occur when the plants were inoculated before this growth stage (at first flowering) because BYMV infection caused plant death. A subsequent experiment in which plants were inoculated at eight different growth stages confirmed that BPS was only induced when L. angustifolius plants were inoculated after first flowering, when pods had formed. Thus, BYMV was isolated from symptomatic L. angustifolius survey samples, inoculated to and maintained in culture hosts, inoculated to healthy L. angustifolius test plants inducing BPS, and then successfully reisolated from them. As such, Koch's postulates were fulfilled for the hypothesis that late infection with BYMV causes BPS in L. angustifolius plants.


A compositional and dynamic model for face aging.
In this paper, we present a compositional and dynamic model for face aging. The compositional model represents faces in each age group by a hierarchical And-Or graph, in which And nodes decompose a face into parts to describe details (e.g., hair, wrinkles, etc.) crucial for age perception and Or nodes represent large diversity of faces by alternative selections. Then a face instance is a transverse of the And-Or graph-parse graph. Face aging is modeled as a Markov process on the parse graph representation. We learn the parameters of the dynamic model from a large annotated face data set and the stochasticity of face aging is modeled in the dynamics explicitly. Based on this model, we propose a face aging simulation and prediction algorithm. Inversely, an automatic age estimation algorithm is also developed under this representation. We study two criteria to evaluate the aging results using human perception experiments: 1) the accuracy of simulation: whether the aged faces are perceived of the intended age group, and 2) preservation of identity: whether the aged faces are perceived as the same person. Quantitative statistical analysis validates the performance of our aging model and age estimation algorithm.


Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.
Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23 and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial.


Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.
Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels.


Cannabis and psychiatric disorders: it is not only addiction.
Since the discovery of the endocannabinoid system, a growing body of psychiatric research has emerged focusing on the role of this system in major psychiatric disorders like schizophrenia (SCZ), bipolar disorder (BD), major depression and anxiety disorder. Continuing in the line of earlier epidemiological studies, recent replication studies indicate that frequent cannabis use doubles the risk for psychotic symptoms and SCZ. Further points of clinical research interest are alterations of endocannabinoids and their relation to symptoms as well as postmortem analyses of cannabinoid CB(1) receptor densities in SCZ. A possible neurobiological mechanism for the deleterious influence of cannabis use in SCZ has been suggested, involving the disruption of endogenous cannabinoid signaling and functioning. Even though the number of studies is still limited for affective and anxiety disorders, previous results suggest these diseases to be exciting objectives of cannabinoid-associated research. Therefore, it became apparent that cannabis use is not only frequent in patients suffering from BD, but that it also induces manic symptoms in this group. In addition, prior antipsychotic treatment decreased the numerical density of CB(1) immunoreactive glial cells in bipolar patients. Although the data on the influence of cannabis use on the development of major depression is controversial, cannabinoid compounds could display a new class of medication, as suggested by the antidepressive effects of the fatty acid amino hydrolase inhibitor URB597 in animal models. With numerous open questions and controversial results, further research is required to specify and extend the findings in this area, which provides a promising target for novel pharmacotherapeutic interventions.


Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED; OMIM 240300) is a rare autosomal recessive disorder defined by a variable combination of endocrine failure, chronic mucocutaneous candidiasis (CMC), and dystrophy of the dental enamel and nails. APECED is caused by mutations in the autoimmune regulator gene (AIRE). Alopecia areata (AA) and vitiligo are diseases with autoimmune pathogeneses, and have been recognized as part of the APECED complex. There are rare reports of other cutaneous manifestations. We sought to delineate the dermatological features of APECED in an Irish case series with emphasis on timing of their appearance and association with disease severity. Furthermore, we looked for evidence of genotype: phenotype correlation. Finally, we wanted to determine if the ectodermal changes described represent a primary ectodermal dysplasia or whether the ectodermal manifestations are secondary phenomena. Irish patients with APECED were invited to attend a multidisciplinary clinic (Dermatology, Endocrinology, Dentistry and Ophthalmology) held in Our Lady's Hospital for Sick Children, Dublin. Clinical data were compiled from case notes and questionnaires. All patients had a detailed cutaneous examination. Blood samples were obtained for mutational analysis. Eighteen patients (seven males and 11 females) from 15 families were interviewed and examined. The mean age at diagnosis was 6 years (range 8 months-18 years). All patients had evidence of CMC, 13 (72%) had candidal onychomycosis or paronychia, six (33%) had AA and two had vitiligo. In the case of two patients the diagnosis was made on recognition of dermatological manifestations and confirmed by mutational analysis. Both patients developed Addison's disease on follow-up. CMC was an early feature, often predating diagnosis (10 of 18). AA and vitiligo presented later, and may reflect more severe disease in these cases. There was no correlation between the AIRE mutations identified on mutational analysis and the clinical presentation. We found no evidence of an isolated nail dystrophy or features consistent with a primary ectodermal dysplasia. APECED is a rare but complex and potentially life-threatening autoimmune disease. CMC is a common and early feature; diagnosis at this stage may pre-empt life-threatening endocrinological crises. It is important for dermatologists to be aware of this association as they are likely to be the earliest clinicians who encounter these children. AA and vitiligo in our series occurred in the setting of established disease. The term "ectodermal dystrophy" is misleading as the ectodermal features described in our series and in the literature are most likely to be secondary phenomena.


Analysis of Giant Intraventricular and Extraventricular Epidermoids, Defining Risk Factors for Recurrence, an Institutional Experience.
Multicompartmental intraventricular epidermoids behave differently from multicompartmental extraventricular lesions and localized lesions during its management. Few studies are available which have analyzed risk factors separately in these groups of cases for recurrence of these lesions and time to recur. In this retrospective observational study, 72 cases of intracranial epidermoid were treated over a span of 7 years. Cases were categorized into three groups. Group 1 comprised 15% (11/72) of cases with intraventricular multicompartmental, Group 2 with 22% (16/72) extraventricular giant tumors with multicompartmental involvement and size >4.5 cm, and Group 3 comprised 63% (45/72) of patients with lesions <4.5 cm and localized. Data pertaining to demography, clinical and radiological features, surgery performed, postoperative complication, histology, and follow-up were obtained from medical records available in the institute. The average duration to treat was 1.86 ± 0.52 (standard deviation [SD]) years, with headache as a major complaint in all the groups. Combined endoscope-assisted microsurgery was performed in 38.8% (28/72), microsurgery in 54.1% (39/72), and endoscopic excision in 6.9% (5/72) of cases. Tumor calcification was found in 23.6% (17/72) and preoperative capsular enhancement was seen in 19.4% (14/72) which persisted in 79% (11/14) of cases postoperatively on subsequent follow-up suggesting recurrence. On stepwise logistic regression analysis, preoperative capsular enhancement was a strong predictor of recurrence of tumor (P = 0.001). The average follow-up was 46 ± 14.92 (SD) months in Group 1, 52.34 ± 11.45 (SD) months in Group 2, and 63.36 ± 18.42 (SD) months in Group 3. Although the intracranial epidermoid is known to recur after long interval, tumor with specific characteristics can recur in short span of 5-6 years. Tumor characteristics such as preoperative capsular enhancement, multicompartmental distribution in vertebrobasilar territory, large size, and presence of calcification are strong predictors for recurrence. Performing endoscope-assisted microsurgery can decrease the postoperative morbidities but does not reduce the recurrence risk.


Nervous system and neural maps in gastropod Helix lucorum L.
The present review summarizes the literature and provides new data concerning nervous system structure and the identification of individual neurons in the snail Helix lucorum. Information about especially well-known neurons is provided in a table, and maps of the identifiable neuron's location in ganglia are correlated with the results of retrograde staining via various cerebral and subesophageal nerves. References concerning the morphology of snail central nervous system and identifiable neurons are given.


Effect of Milk Fermented with Lactobacillus fermentum on the Inflammatory Response in Mice.
Currently, the effect of fermented milk on the T-helper 17 response in inflammatory bowel diseases (IBDs) is unknown. The aim of the present study was to evaluate the effect of milks fermented with Lactobacillus fermentum on the Th1/Th17 response in a murine model of mild IBD. Exopolysaccharide (EPS), lactic acid (LA), and total protein (TP) contents and bacterial concentration were determined. Male C57Bl/6 mice intragastrically received either raw (FM) or pasteurized (PFM) fermented milk before and during a dextran sulfate infusion protocol. Blood, spleen, and colon samples were collected at Weeks 6 and 10. IL-6, IL-10, and TNFα were determined in serum, and IL-17, IL-23, and IFNγ were determined in intestinal mucosa and serum. The FM groups did not differ in cell concentration, LA, or TP content (p > 0.05); FM-J28 had the highest EPS content. Spleen weight and colon length did not differ among the FM groups (p > 0.05). In the FM-J20 and PFM-J20 groups, IL-17 and IFNγ decreased, and the IL-10 concentration was enhanced (p < 0.05) at Week 6. IL-6, TNFα, IL-23, and IFNγ did not differ in serum and mucosa (p > 0.05), and IL-17 was lowest in FM-J28 and FM-J20. Therefore, FM appears to potentially play a role in decreasing the Th17 response. However, further studies are needed to elucidate the FM-mediated anti-inflammatory mechanisms in IBD.


Pros and cons of different stunning methods from a Halal perspective: a review.
There has always been a debate about the acceptability of stunning methods for preparing Halal slaughtered meat. Throughout the last few decades, stunning methods have become acceptable for Halal slaughtering due to an increasing majority of Muslim countries issuing Fatwas (religious rulings) that approve of stunning methods for the Halal slaughtering of food animals. With an increasing Muslim population worldwide, Halal meat provision is important for Muslims both economically and ethically. Moreover, there have been concerns regarding traditional Halal slaughter without the use of stunning from the standpoint of the animal's welfare. This article reviews the different stunning methods available and the associated processing practices, addressing their pros and cons in the commercial production of Halal meat.


Detection of the gp43 gene and (1-3)-beta-D-glucan of Paracoccidioides brasiliensis in the blood of experimentally infected mice.
Paracoccidioidomycosis (PCM) is a deep mycosis caused by the thermo-dependent dimorphic fungus Paracoccidioides brasiliensis and is prevalent in Latin American countries. Diagnosis of PCM is sometimes difficult outside the endemic countries, thus a rapid and conclusive method for diagnosis of PCM has been anticipated. We compared the sensitivities of a nested PCR method for detecting the gp43 gene and a commercial kit for detecting (1-3)-beta-D-glucan in the blood of experimentally infected mice. Blood samples were collected from mice at 0 (soon after inoculation), 6, 12, 24, 48, and 72 hours and 5, 7, 10, 14, 17, 21, 24, 28 and 56 days after the intravenous inoculation of 10(6) yeast cells of P. brasiliensis, and were separated into clots and plasma. The (1-3)-beta-D-glucan detection kit in the plasma showed positive reactions in some samples within 7 days and 28 and 56 days after infections. In contrast, the PCR method was more sensitive than the (1-3)-beta-D-glucan detection kit throughout the observation period. The clot samples yielded more sensitive PCR-results than did the plasma samples. Although 24 hours is required for the PCR detection, it was confirmed to provide an accurate diagnosis of PCM.


Downregulation of TBC1 Domain Family Member 24 (BC1D24) Inhibits Breast Carcinoma Growth via IGF1R/PI3K/AKT Pathway.
BACKGROUND TBC1 domain family member 24 (TBC1D24) pathogenic mutations affect its binding to ARF6 and then result in severe impairment of neuronal development. However, there are no reports about the expression and function of TBC1D24 in cancer. The aim of the present study was to evaluate the effect of proliferation, migration, and invasion after silencing TBC1D24 expression in breast cancer MCF-7 cells, and to elucidate the potential mechanism of TBC1D24 in breast cancer. MATERIAL AND METHODS The expression of TBC1D24 in breast cancer tissues and the adjacent non-tumor tissues was determined by S-P immunohistochemistry. The malignant behavior, including proliferation, migration, and invasion ability, was determined after silencing TBC1D24 in breast cancer MCF-7 cells. The expression of IGF1R was determined after silencing TBC1D24. The expression of TBC1D24 and IGF1R was detected after transfecting miR-30a mimics or inhibitors. The effect of TBC1D24 on MCF-7 cells growth in vivo was evaluated by a tumor xenograft study. RESULTS TBC1D24 expression was elevated and was associated with poor outcome in breast carcinoma. TBC1D24 high expression was significantly correlated with unfavorable OS and RFS for breast cancer patients (p<0.05). Silencing TBC1D24 inhibited the proliferation, migration, and invasion ability of MCF-7 cells. TBC1D24 and IGF1R expression were decreased when transfected with miR-30a mimics. However, TBC1D24 and IGF1R expression were increased when transfected with miR-30a inhibitors (p<0.05). Knockdown of TBC1D24 inhibited the expression of IGF1R, PI3K, and p-AKT (p<0.05). Knockdown of TBC1D24 abolished tumorigenicity of MCF-7 cells. The average volume and weight of tumors was lower after silencing TBC1D24 expression (P<0.05). CONCLUSIONS Silencing TBC1D24 inhibited MCF-7 cells growth in vitro and in vivo. TBC1D24 promoted breast carcinoma growth through the IGF1R/PI3K/AKT pathway. TBC1D24 is a potential therapeutic target for breast cancer.


Improving Risk Identification of Adverse Outcomes in Chronic Heart Failure Using SMOTE+ENN and Machine Learning.
This study sought to develop models with good identification for adverse outcomes in patients with heart failure (HF) and find strong factors that affect prognosis. A total of 5004 qualifying cases were selected, among which 498 cases had adverse outcomes and 4506 cases were discharged after improvement. The study subjects were hospitalized patients diagnosed with HF from a regional cardiovascular hospital and the cardiology department of a medical university hospital in Shanxi Province of China between January 2014 and June 2019. Synthesizing minority oversampling technology combined with edited nearest neighbors (SMOTE+ENN) was used to pre-process unbalanced data. Traditional logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) were used to build risk identification models, and each model was repeated 100 times. Model discrimination and calibration were estimated using F1-score, the area under the receiver-operating characteristic curve (AUROC), and Brier score. The best performing of the five models was used to identify the risk of adverse outcomes and evaluate the influencing factors. The SME-XGBoost was the best performing model with means of F1-score (0.3673, 95% confidence interval [CI]: 0.3633-0.3712), AUC (0.8010, CI: 0.7974-0.8046), and Brier score (0.1769, CI: 0.1748-0.1789). Age, N-terminal pronatriuretic peptide, pulmonary disease, etc. were the most significant factors of adverse outcomes in patients with HF. The combination of SMOTE+ENN and advanced machine learning methods effectively improved the discrimination efficacy of adverse outcomes in HF patients, accurately stratified patients at risk of adverse outcomes, and found the top factors of adverse outcomes. These models and factors emphasize the importance of health status data in determining adverse outcomes in patients with HF.


Links between motor control and classroom behaviors: Moderation by low birth weight.
It is unclear from past research on effortful control whether one of its components, motor control, independently contributes to adaptive classroom behaviors. The goal of this study was to identify associations between early motor control, measured by the walk-a-line task at age 3, and teacher-reported learning-related behaviors (approaches to learning and attention problems) and behavior problems in kindergarten classrooms. Models tested whether children who were vulnerable to poorer learning behaviors and more behavior problems due to having been born low birth weight benefited more, less, or the same as other children from better motor control. Data were drawn from the national Fragile Families and Child-Wellbeing Study (n = 751). Regression models indicated that motor control was significantly associated with better approaches to learning and fewer behavior problems. Children who were low birth weight benefitted more than normal birth weight children from better motor control with respect to their approaches to learning, but equally with respect to behavior problems. Additionally, for low but not normal birth weight children, better motor control predicted fewer attention problems. These findings suggest that motor control follows a compensatory model of development for low birth weight children and classroom behaviors.


Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain.
The zinc-binding Bbox1 domain in protein MID1, a member of the TRIM family of proteins, facilitates the ubiquitination of the catalytic subunit of protein phosphatase 2A and alpha4, a protein regulator of PP2A. The natural mutation of residue A130 to a valine or threonine disrupts substrate recognition and catalysis. While NMR data revealed the A130T mutant Bbox1 domain failed to coordinate both structurally essential zinc ions and resulted in an unfolded structure, the unfolding mechanism is unknown. Principle component analysis revealed that residue A130 served as a hinge point between the structured β-strand-turn-β-strand (β-turn-β) and the lasso-like loop sub-structures that constitute loop1 of the ββα-RING fold that the Bbox1 domain adopts. Backbone RMSD data indicate significant flexibility and departure from the native structure within the first 5 ns of the molecular dynamics (MD) simulation for the A130V mutant (>6 Å) and after 30 ns for A130T mutant (>6 Å). Overall RMSF values were higher for the mutant structures and showed increased flexibility around residues 125 and 155, regions with zinc-coordinating residues. Simulated pKa values of the sulfhydryl group of C142 located near A130 suggested an increased in value to ~9.0, paralleling the increase in the apparent dielectric constants for the small cavity near residue A130. Protonation of the sulfhydryl group would disrupt zinc-coordination, directly contributing to unfolding of the Bbox1. Together, the increased motion of residues of loop 1, which contains four of the six zinc-binding cysteine residues, and the increased pKa of C142 could destabilize the structure of the zinc-coordinating residues and contribute to the unfolding.


Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic, immunohistochemical, and clinical analyses.
Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.


The effects of laparoscopic urologic surgery on cardiac functions: A pulse wave velocity study.
The aim of this study is to evaluate the effects of laparoscopic urologic surgery on cardiac functions by the parameter pulse wave velocity (PWV), a noninvasive method. Between July 2012 and February 2013, a total of 47 patients were included in this prospective controlled study. Patients who have been scheduled for laparoscopic surgery (LS) (n=30) and open surgery (n=17) were enrolled in the study. Preoperative, perioperative, and postoperative cardiovascular parameters were measured by a PWV instrument, and the results were compared between laparoscopic (L) group and open (C) group. In the L group, compared to preoperative values, perioperative systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure increased considerably, by 2.6%, 7.9%, and 4.7%, respectively. This was in contrary to reductions in these parameters by 9.5%, 5.7%, and 10%, respectively, in the C group. For the L group, cardiac output (CO) and cardiac index (CI) were increased in the perioperative period and decreased in the postoperative period. For the C group, there were no changes in measurements of perioperative and postoperative CO and CI. However, these changes in CO and CI were not significantly different between the L and C groups. Postoperative large artery elasticity index decreased in both groups. However, these changes did not represent significant difference between groups. Compared to open surgery, LS may cause increases in perioperative blood pressures. In addition, increased blood pressures may last even on the first postoperative day. These effects may be more important for patients with high cardiovascular risk.


The sensitivity of cardiac markers: an evidence-based approach.
The aim of this study was to determine whether, using an evidence-based approach, the results of the papers found in the literature are valid and sufficiently scientifically rigorous to be used to definitely address the problem of cardiac marker sensitivity in detection of acute myocardial infarction. In particular, the diagnostic sensitivities of myoglobin, creatine kinase (CK)-MB isoenzyme, determined as mass concentration, CK-MB isoforms, and of the two cardiac troponins, troponin I and troponin T, were reviewed using a priori formulated inclusion/exclusion criteria for judging the eligibility of studies to be included in the analysis. A clear final message derived from this systematic analysis is the unacceptably poor diagnostic sensitivity of all evaluated markers at patient admission, with substantial failure rate to rule out myocardial infarction at this time. Myoglobin is at present the most sensitive of the markers studied for excluding early AMI with an optimum timing of sampling at patient presentation and approximately 4 h later. However, this marker cannot be used by itself as a proportion of patients admitted to the hospital with a late infarction could be missed. The early rate of rise of CK-MB mass and troponin T is similar. Maximum sensitivity of these two parameters is achieved by the analysis of a second sample 6 to 12 h after admission. Additional larger studies are needed to address the question which troponin shows earlier release after myocardial damage, and to clarify the role of CK-MB isoforms as a possible early marker of myocardial infarction.


Water mass and depth determine the distribution and diversity of Rhodobacterales in an Arctic marine system.
Marine Rhodobacterales are recognized as a widespread, abundant, and metabolically versatile bacterial group in the world's oceans. They also show a nearly universal conservation of the genes for production of gene transfer agents (GTAs), virus-like particles that mediate genetic exchange between cells. It is not yet clear what factors determine the distribution of the various taxonomic subgroups of this order. To address this question, we analyzed the Rhodobacterales communities in 10 seawater samples from northern Baffin Bay collected during September 2008. A conserved gene from the GTA gene cluster was used to characterize the Rhodobacterales community structure. A total of 320 clones from 10 clone libraries were sequenced, and 22 operational taxonomic units representing putative species and 13 clusters representing putative genera were identified. A cluster related to Octadecabacter comprised 59% of total clones from the northern Baffin Bay. Phylogenetic analysis of the clones showed that the Rhodobacterales communities had distinct compositions in the different water masses that were sampled. A change in community structure related to depth was also observed. Therefore, in northern Baffin Bay where two ocean currents meet and mix, the Rhodobacterales community structures were primarily determined by water mass and depth.


[Radionuclide methods in planning treatment for uterine cancer].
Indirect low radionuclide lymphography with 113mIn-coindium and serial renoscintigaphy with 131mI-hippuran were done to 103 patients with cancer of the uterus. A high diagnostic value of radionuclide methods was shown. In a comparative analysis of radiolymphography and direct roentgenocontrast lymphography with the results of a morphological study of the lymph nodes the informative value was 70.7% for the radionuclide and 75% for the x-ray studies of the lymphatic system. A higher sensitivity of serial renoscintigraphy as compared to excretory urography (34.2% and 27.6% respectively) was shown in the diagnosis of pathology of the urinary system. Taking into account the absence of counterindications to and the simplicity of radionuclide studies it is recommended that they should be included in the complex of diagnostic procedures for patients with cancer of the uterus.


Rehabilitation of asyntactic comprehension in post-stroke aphasic individuals: A systematic review of the literature
Asyntactic comprehension corresponds to a disorder in the comprehension of sentences, which is one of the difficulties that can arise in a context of aphasia following a stroke. To date, rehabilitation of asyntactic comprehension is divided into three main groups of approaches, centered on the structure of the sentence, on the memory or on the verb and its thematic roles. The present study aims to assess the effectiveness of the existing treatments to rehabilitate asyntactic comprehension in post-stroke aphasic individuals, in terms of post-treatment improvements, generalization, long-term maintenance and transfer effects to daily life activities. A systematic review of the literature was carried out and twenty-four studies presenting seven different treatments, were selected, involving a total of 148 post-stroke aphasic patients. The methodological quality of each study has been analyzed following the Santiago-Delefosse grid or the MMAT grid. In general, the analysis of the measures of effectiveness (post-treatment improvement, generalization, maintenance, and transfer effects) showed that the treatments whose approach was centered on the structure of the sentence or on the working memory are those allowing to significantly improve syntactic comprehension for individuals with aphasia. The short-term memory approach did not show improvement in syntactic comprehension but remains little studied. And the approach based on the verb and its thematic roles is so far too understudied to draw a clear conclusion. The present study contributes to the advancement of knowledge on syntactic rehabilitation in the context of post-stroke aphasia leadind to various clinical implications for an informed choice. The few studies available on the subject as well as the few data collected constitute, among other things, a limit to this study.


Root structure and functioning for efficient acquisition of phosphorus: Matching morphological and physiological traits.
Global phosphorus (P) reserves are being depleted, with half-depletion predicted to occur between 2040 and 2060. Most of the P applied in fertilizers may be sorbed by soil, and not be available for plants lacking specific adaptations. On the severely P-impoverished soils of south-western Australia and the Cape region in South Africa, non-mycorrhizal species exhibit highly effective adaptations to acquire P. A wide range of these non-mycorrhizal species, belonging to two monocotyledonous and eight dicotyledonous families, produce root clusters. Non-mycorrhizal species with root clusters appear to be particularly effective at accessing P when its availability is extremely low. There is a need to develop crops that are highly effective at acquiring inorganic P (Pi) from P-sorbing soils. Traits such as those found in non-mycorrhizal root-cluster-bearing species in Australia, South Africa and other P-impoverished environments are highly desirable for future crops. Root clusters combine a specialized structure with a specialized metabolism. Native species with such traits could be domesticated or crossed with existing crop species. An alternative approach would be to develop future crops with root clusters based on knowledge of the genes involved in development and functioning of root clusters. Root clusters offer enormous potential for future research of both a fundamental and a strategic nature. New discoveries of the development and functioning of root clusters in both monocotyledonous and dicotyledonous families are essential to produce new crops with superior P-acquisition traits.


Management of tracheal stenosis after corrosive acid ingestion: A case report.
Although corrosive injury of the digestive tract is a well-known clinical entity, damages of the airway and a critically life-threatening condition, have not been clearly documented. Tracheal stenosis is very rare associated with corrosive acid ingestion. We report the case of a 4-year-old girl child who presented to the emergency department three weeks after accidentally drinking an acidic cleaning agent stored in an unlabeled bottle. Rigid bronchoscopy was administered to observe the stenosis. She was treated by serial dilation, repair of tracheal laceration, and placement of a temporary polyurethane-coated nitinol stent. Careful and accurate stent placement may provide significant and life-saving airway improvement as observed in the presenting pediatric case.


Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis.
According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684-0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462-0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2-7% risk of 2 grades misclassification. These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy.


[Community structure of macrozoobenthos and its relationship with environmental factors in Lake Gehu, Jiangsu, China.]
A survey on macrozoobenthos was conducted seasonally and 14 aquatic physicochemical parameters were monitored monthly to reveal the community characteristics of macrozoobenthos and their relationship with aquatic environmental factors at 20 sampling sites in the Lake Gehu from July 2013 to December 2014. A total of 25 macrozoobenthos species including 3 species (12% of total) of Mollusca, 12 species (48%) of Chironomidae, 4 species (16%) of Oligochaeta, 4 species (16%) of Crustacean were identified. The dominant species were Limnodrilus hoffmeisteri, Branchiuras owerbyi, Tanypus chinensis, and Propsilocerus taihuensis. Density and biomass of Chironomid larvae and Oligochata had significant spatial and seasonal changes. The state of aquatic environment was mainly affected by the nitrogen, phosphorus and water temperature in the Lake Gehu, and TN, NO3--N and DO changed significantly with space and season. The Spearman correlation analysis indicated that TN and NO3--N played a key role in the community structure characteristics of the macrozoobenthos in the Lake Gehu. The environmental variables could well explain the changes of main macrobenthic species.


Decomposing total IR spectra of aqueous systems into solute and solvent contributions: a computational approach using maximally localized Wannier orbitals.
The theoretical principles underpinning the calculation of infrared spectra for condensed-phase systems in the context of ab initio molecular dynamics have been recently developed in literature. At present, most ab initio molecular dynamics calculations are restricted to relatively small systems and short simulation times. In this paper we devise a method that allows well-converged results for infrared spectra from ab initio molecular dynamics simulations using small systems and short trajectories characteristic of simulations typically performed in practice. We demonstrate the utility of our approach by computing the imaginary part of the dielectric constant epsilon"(omega) for H2O and D2O in solid and liquid phases and show that it compares well with experimental data. We further demonstrate that maximally localized Wannier orbitals can be used to separate the individual contributions of different molecular species to the linear spectrum of complex systems. The new spectral decomposition method is shown to be useful in present-day ab initio molecular dynamics calculations to compute the magnitude of the "continuous absorption" generated by excess protons in aqueous solutions with good accuracy even when other species present in the solutions absorb strongly in the same frequency window.


Impact of peak estradiol levels on reproductive outcome of intracytoplasmic sperm injection.
To observe effect of peak estradiol (E2) levels on outcome after intra cytoplasmic sperm injection (ICSI). Quasi experimental design conducted in "Islamabad Clinic Serving Infertile Couples" from June 2010 till August 2011. Down regulation with mid luteal suppression of 564 females aged 18-41 years was done with gonadotrophin releasing hormone agonist followed by controlled ovarian stimulation, ovulation induction (OI), oocytes pickup and embryo transfer. Samples for peak serum E2 at the time of OI was estimated by Enzyme Linked Immuno Sorbent Assay. The association of peak E2 with outcome groups of Intracytoplasmic sperm injection (ICSI) (Group I) beta hCG <5 m IU/ml, (Group II) with beta hCG>5 mI U/ml and no cardiac activity and (Group III) with beta hCG>5mIU/ml and cardiac activity on trans vaginal scan was identified. Statistical comparison by one way analysis of variance (ANOVA) via SPSS version 15 was done. A clinical pregnancy rate of 36% was achieved, pregnant females(Group III) had higher peak E2 2269 ± 80.97 as compared to 1419 ± 37.07 and 1807±90.28 pg/ml (mean ± SD) in Groups I and II respectively (p<0.0001) Elevated serum E2 was significantly associated with better oocyte recovery, fertilization, cleavage and implantation rates (p<0.0001) . A high serum E2 measured on OI day can predict success of treatment after ICSI. Females who had high peak E2 had greater number of retrieved, mature and fertilized oocytes with thick endometrial lining that helped in implantation and clinical pregnancy.


Gut Microbiota and Lifestyle Interventions in NAFLD.
The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed "dysbiosis", has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gut microbiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host-microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gut microbiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gut microbiota and how this impacts upon NAFLD prognosis.


The effect of therapeutic exercise and mobilization on patients with shoulder dysfunction : a systematic review with meta-analysis.
Systematic review with meta-analysis. To pool and summarize the published research evidence examining if the combination of therapeutic exercise and joint mobilization is more beneficial than therapeutic exercise alone in patients with shoulder dysfunction. Therapeutic exercise is an effective intervention for patients with shoulder dysfunction, which is often supplemented by joint mobilization techniques. Numerous studies have examined the effects of the combination of therapeutic exercise and joint mobilization on patients with shoulder dysfunction. Six databases were searched for randomized controlled trials. All the randomized controlled trials published in English that have studied the effectiveness of therapeutic exercise and joint mobilization on adults with either clinically or radiographically confirmed shoulder dysfunction resulting in pain, restriction of range of motion (ROM), and/or limitation in function, were included in this review. Effect size was calculated in the form of standardized mean difference and 95% confidence interval (CI) for each variable, then combined to represent weighted standardized mean differences (WSMDs) and 95% CIs. Seven studies that met the inclusion criteria were identified, with a total of 290 participants. The WSMDs and CIs, which combined the results of all the studies for a particular variable, revealed equivocal results for all variables. The resulting WSMD (95% CI) for each of the variables was 0.2 (-0.68, 1.08) for pain, 0.15 (-0.67, 0.97) for abduction ROM, -0.04 (-0.65, 0.57) for flexion ROM, 0.01(-0.79, 0.81) for internal and external rotation ROM, and 0.09 (-0.46, 0.64) for function and disability. Even after elimination of sources of heterogeneity, the new WSMDs and CIs continued to overlap zero, giving equivocal results. The current evidence is inconclusive with respect to the beneficial effects of the combination of therapeutic exercise and joint mobilization versus therapeutic exercise alone for reducing pain, increasing ROM and function, and limiting disability in patients with shoulder dysfunction. Therapy, level 1a-.


Spatial patterns of gene expression in the extramatrical mycelium and mycorrhizal root tips formed by the ectomycorrhizal fungus Paxillus involutus in association with birch (Betula pendula) seedlings in soil microcosms.
Functional compartmentation of the extramatrical mycelium of ectomycorrhizal (ECM) fungi is considered important for the operation of ECM associations, although the molecular basis is poorly characterized. Global gene expression profiles of mycelium colonizing an ammonium sulphate ((NH4)2SO4) nutrient patch, rhizomorphs and ECM root tips of the Betula pendula-Paxillus involutus association were compared by cDNA microarray analysis. The expression profiles of rhizomorphs and nutrient patch mycelium were similar to each other but distinctly different from that of mycorrhizal tips. Statistical analyses revealed 337 of 1075 fungal genes differentially regulated among these three tissues. Clusters of genes exhibiting distinct expression patterns within specific tissues were identified. Genes implicated in the glutamine synthetase/glutamate synthase (GS/GOGAT) and urea cycles, and the provision of carbon skeletons for ammonium assimilation via beta-oxidation and the glyoxylate cycle, were highly expressed in rhizomorph and nutrient patch mycelium. Genes implicated in vesicular transport, cytoskeleton organization and morphogenesis and protein degradation were also differentially expressed. Differential expression of genes among the extramatrical mycelium and mycorrhizal tips indicates functional specialization of tissues forming ECM associations.


Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity.
NP-1, a candidacidal peptide purified from rabbit granulocytes, bound extensively and with biphasic kinetics to Candida albicans. The primary phase of binding was temperature independent and occurred even at 0 degrees C. This primary binding was relatively specific, reversible, saturable, and of high capacity. It was inhibited by increased salt concentrations in the incubation medium, but was relatively unaffected by increasing the calcium ion concentration or by lowering the incubation temperature to 0 degrees C. The secondary phase of binding was only noted under conditions that supported candidacidal activity. Secondary binding was inhibited by millimolar concentrations of calcium, but not magnesium, ions and did not occur at 0 degrees C or when subtoxic concentrations of NP-1 were tested. NP-2 and NP-3a, other potent candidacidal peptides from rabbit granulocytes, also bound directly and extensively to C. albicans and competed for binding with NP-1. NP-4 and NP-5, less candidacidally active homologs of the aforementioned peptides, showed relatively little direct binding activity and competed poorly for binding with NP-1 or NP-2. NP-3b, another less candidacidal homolog, bound extensively to C. albicans, but did not compete effectively with NP-1 or NP-2. By comparing candidacidal and binding activity of the peptides, we conclude that the candidacidal activity of NP-1 involves primary binding to C. albicans followed by postbinding events that are temperature dependent and inhibitable by calcium ions.


ABCD-treatment of a propagating doughnut beam generated by a spiral phase plate.
We apply the Collins-Huygens integral to analytically describe propagation of a doughnut beam generated by a spiral phase plate. Measured beam profiles in free space and through an ABCD-lens system illustrate excellent agreement with theory. Applications range from the creation of optical beams with angular momentum to microscopy to trapping neutral atoms. The method extends to other beam shaping components, too.


Artificially modified magnetic anisotropy in interconnected nanowire networks.
Interconnected or crossed magnetic nanowire networks have been fabricated by electrodeposition into a polycarbonate template with crossed cylindrical nanopores oriented ±30° with respect to the surface normal. Tailor-made nanoporous polymer membranes have been designed by performing a double energetic heavy ion irradiation with fixed incidence angles. The Ni and Ni/NiFe nanowire networks have been characterized by magnetometry as well as ferromagnetic resonance and compared with parallel nanowire arrays of the same diameter and density. The most interesting feature of these nanostructured materials is a significant reduction of the magnetic anisotropy when the external field is applied perpendicular and parallel to the plane of the sample. This effect is attributed to the relative orientation of the nanowire axes with the applied field. Moreover, the microwave transmission spectra of these nanowire networks display an asymmetric linewidth broadening, which may be interesting for the development of low-pass filters. Nanoporous templates made of well-defined nanochannel network constitute an interesting approach to fabricate materials with controlled anisotropy and microwave absorption properties that can be easily modified by adjusting the relative orientation of the nanochannels, pore sizes and material composition along the length of the nanowire.


Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease.
There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.


DNA typing of the human MN and Ss blood group antigens in amniotic fluid and following massive transfusion.
Although red blood cell (RBC) antigen typing by agglutination is generally useful, several situations exist where this approach is difficult or impossible. For example, following a massive transfusion, a patient's residual RBCs are mixed with transfused normal donor RBCs. In this case, typing by hemagglutination primarily detects the antigens on the heterogeneous population of transfused RBCs. Agglutination testing is also of limited use for determining the phenotype of a fetus at risk for hemolytic disease of the newborn because fetal RBCs must be obtained by periumbilical blood sampling. Determining the genotype of an individual by analyzing genomic DNA isolated from peripheral blood nucleated cells or amniocytes is an alternative approach for determining the RBC antigen type. In this report, the allele specific polymerase chain reaction (AS-PCR) was used to identify the alleles at the MN and Ss loci that encode the corresponding antigens on glycophorin A (GPA) and glycophorin B (GPB), respectively. This method was used to type these alleles in peripheral blood samples obtained from normal individuals and from patients following massive transfusion. Of 23 peripheral blood specimens analyzed, all were correctly typed by this method. The allele specific polymerase chain reaction was also used to determine these alleles using amniotic fluid samples. Of 11 amniotic fluid specimens analyzed, 8 were correctly typed at both loci. Mistyping of three amniotic fluid specimens was explained by possible maternal blood contamination.


Career choices of the first seven cohorts of JCU MBBS graduates: producing generalists for regional, rural and remote northern Australia.
Generalism in the health workforce has been established as an important strategy to address health workforce maldistribution. Thus, to best serve the medical needs of northern Australia, the James Cook University (JCU) College of Medicine and Dentistry has a mission to produce graduates who both practise in the region and have a generalist orientation. This study investigated the postgraduate qualifications and key factors that shaped the current career choice of JCU medical graduates, and whether JCU graduates are more likely to choose generalist careers than other Australian medical practitioners of a similar level of experience. JCU medical graduate data were obtained via cross-sectional survey of 298 early career JCU medical graduates from postgraduate year (PGY) 4 to PGY 10 (the first seven cohorts) who had consented to be contacted for further studies and were still contactable (n=180, response rate=60%). Australian medical graduate data were obtained via the National Health Workforce Dataset released by the Department of Health. Compared to a group of Australian medical graduates with similar years of experience, JCU medical graduates are significantly more likely to choose careers as 'generalists' (general practitioners/rural generalists (p=0.044)) or 'generalist specialists' in general surgery (p=0.008), general paediatrics (p=0.008), obstetrics and gynaecology (p=0.038) and emergency medicine (borderline significance p=0.058). However, they are less likely to be 'specialist specialists' such as pathologists/radiologists (p=0.003) or a physician subspecialty (p=0.004). Key factors identified as influencing current career choice included 'interest developed or strengthened during undergraduate training', 'interest developed from early postgraduate career experiences', 'specialty has a good work-life balance', 'specialty involves continuity of care with patients', 'interest in rural practice', 'enjoy a wide scope of practice/being a generalist' and 'mentors'. The JCU medical school produces significantly more graduates with a generalist rather than specialist career focus compared to a similarly experienced group of Australian medical practitioners. Contributing factors may include the JCU selection process, and the curricular focus on providing students with a wide range of generalist experiences and exposure to rural, remote, Indigenous and tropical health. Developing approaches that facilitate local vocational training and subsequent specialist practice is also an important part of the regional, rural and remote training pathway. Lastly, the findings suggest JCU medical graduates choose a career that is not only compatible with regional, rural or remote practice, but also involves continuity of care with patients, a wide scope of practice and a good work-life balance, and that this choice has been influenced by a combination of undergraduate and early career experiences. These findings are in line with international evidence and have implications for other jurisdictions planning an educational and workforce strategy to meet the needs of their own regional, rural and remote locations.


Evidence for a novel role for dachshund in patterning the proximal arthropod leg.
The branchiopod crustacean Triops longicaudatus has paddlelike thoracic appendages with few joints and multiple marginal lobes. Here, we explore the degree to which the Triops limb is patterned by the same network of genes known to pattern the uniramous, multi-jointed insect appendage. Insect leg patterning proceeds through a process of subdividing the leg into proximal, intermediate, and distal regions by the activity of the transcription factors hth/exd, dac, and Dll. The immature Triops limb is subdivided into large, discrete regional domains (proximal and distal) as defined by nuclear-EXD and DLL. We show that HTH expression in Triops overlaps cell-to-cell with n-EXD expression. In addition, dac is expressed in two domains: (1) adjacent to and partially overlapping the distal Dll domain and (2) along the medial margin of the developing leg. The DAC domain adjacent to the distal Dll domain supports the early establishment of the expected intermediate domain of DAC expression. The medial expression domain resolves over time into a series of reiterated stripes located on the lower side of each medial lobe. Later, this expression pattern correlates with the sclerotized regions associated with limb flexion. We propose that these stripes of DAC expression play a role in forming reiterated medial lobes. Unlike Drosophila, where the proximal distal patterning of the leg is coincident with patterning of reiterated structures (segments), we hypothesize that the patterning in Triops may reflect an ancestral state where the patterning of reiterated medial structures was not coincident with proximodistal limb patterning.


Surface plasmon fluorescence measurements of human chorionic gonadotrophin: role of antibody orientation in obtaining enhanced sensitivity and limit of detection.
This paper describes the determination of limits of detection (LODs) of interactions between an antigen, human chorionic gonadotrophin (hCG), and antibodies, anti-alpha-hCG and anti-beta-hCG, using a sandwich assay by surface plasmon field-enhanced fluorescence spectroscopy (SPFS). Randomly biotinylated antibodies were adsorbed onto a structured self-assembled monolayer (SAM)-streptavidin matrix, tethered to gold via a SAM consisting of biotinylated thiol molecules interspersed with hydroxyalkanethiol molecules. The influence of the concentration of biotinylated thiol on the binding of biotinylated antibody and its functionality, in terms of its ability to bind to the hCG antigen, was studied. This allowed determination of the optimum biotin-thiol mole fraction in the mixed thiol solution and consequently in the SAM, to maximize binding of hCG of the streptavidin-bound antibody. SPFS studies of the binding of a secondary fluorescently labeled antibody to hCG immobilized on the optimized SAM-streptavidin-antibody layer showed that a LOD of hCG of 2 mIU mL(-1) (4 x 10(-12) mol L(-1)) could be realized. The system was further optimized by using a more oriented and organized surface by adsorbing monobiotinylated Fab-hCG in place of the whole antibody. A LOD of 0.3 mIU mL(-1) (6 x 10(-13) mol L(-1)) was achieved for this system. This work illustrates the importance of antibody orientation, both on the planar surface and in terms of position of binding site, in maximizing sensor sensitivity.


Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility.
Ca2+ influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here, we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+ indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+ along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+ signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+ transients: short-duration 'sparkles' and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.


Development and validation of nomogram to predict risk of survival in patients with laryngeal squamous cell carcinoma.
To the best of our knowledge, this is the first study established a nomogram to predict survival probability in Asian patients with LSCC. A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application. Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intent surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in the present study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models' concordance. The C-index of the nomogram was 0.73 (0.68-0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage. A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.


Mexiletine or catheter ablation after amiodarone failure in the VANISH trial.
In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.


Transcriptional and proteomic analysis of the Aspergillus fumigatus ΔprtT protease-deficient mutant.
Aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. The fungus invades the lungs and other organs, causing severe damage. Penetration of the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases to degrade the host structural barriers. The A. fumigatus transcription factor PrtT controls the expression of multiple secreted proteases. PrtT shows similarity to the fungal Gal4-type Zn(2)-Cys(6) DNA-binding domain of several transcription factors. In this work, we further investigate the function of this transcription factor by performing a transcriptional and a proteomic analysis of the ΔprtT mutant. Unexpectedly, microarray analysis revealed that in addition to the expected decrease in protease expression, expression of genes involved in iron uptake and ergosterol synthesis was dramatically decreased in the ΔprtT mutant. A second finding of interest is that deletion of prtT resulted in the upregulation of four secondary metabolite clusters, including genes for the biosynthesis of toxic pseurotin A. Proteomic analysis identified reduced levels of three secreted proteases (ALP1 protease, TppA, AFUA_2G01250) and increased levels of three secreted polysaccharide-degrading enzymes in the ΔprtT mutant possibly in response to its inability to derive sufficient nourishment from protein breakdown. This report highlights the complexity of gene regulation by PrtT, and suggests a potential novel link between the regulation of protease secretion and the control of iron uptake, ergosterol biosynthesis and secondary metabolite production in A. fumigatus.


[Cytogenetic study of synapsis and crossing-over in male mice heterozygous for reciprocal translocation T(14; 15)6Ca].
Synapsis and crossing over in male mice heterozygous for reciprocal translocation T (14; 15)6Ca were studied. The translocated multivalent undergoes the synaptic adjustment in the course of meiotic prophase. Translocated distal region of the 14th chromosome forms inproportionally long lateral element of synaptonemal complex. The number of chiasmata in the 14th chromosome increases from 1.02 0.02 in normal karyotype to 1.41 0.03 in heterozygous mice. The density of chiasmata in translocated, distal region is ten times higher than in the other part of the 14th chromosome.


The menstrual cycle and drug metabolism.
Within the field of drug metabolism, when addressing quantitative aspects, an average value is traditionally quoted, commonly the arithmetic mean with perhaps an indication of spread. Better still a range of values may be given, thereby acknowledging that various factors may precipitate differences between individuals. A single subject, however, usually only merits a single value. Nevertheless, events such as an acute illness or concurrent drug therapy serve to alert that this value may change substantially over a relatively short time-period, although any potential effects of naturally occurring phenomena, such as the female menstrual cycle, are often overlooked or disregarded. Are the biochemical and physiological changes that occur during the menstrual cycle able to influence xenobiotic metabolism? Is the idea of a stable and unwavering baseline within a single healthy individual flawed? Is it time to reassess our thinking with regards to such aspects? This brief review explores these issues and examines information available within the literature for evidence of potential influences of menstrual cycle events upon drug metabolism, defined as the actual chemical alteration of the parent molecule into another chemical species.


Nitric oxide initiates progression of human melanoma via a feedback loop mediated by apurinic/apyrimidinic endonuclease-1/redox factor-1, which is inhibited by resveratrol.
It is well recognized that nitric oxide (NO) is involved in tumor progression, including melanoma. Measurement of proliferative and metastatic capacity by MTS and Matrigel invasion assays, respectively, was done and showed that NO-treated melanoma cells exhibited a higher capacity compared with control, especially metastatic Lu1205 cells. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) is a multifunctional protein and its role in tumor biology has attracted considerable attention. To determine whether APE/Ref-1 plays a role in mediating NO stimulation of melanoma progression, we investigated the effect of DETA/NO on levels of APE/Ref-1 and related downstream targets [activator protein-1 (AP-1)/JunD, matrix metalloproteinase-1 (MMP-1), Bcl-2, and inducible nitric oxide synthase (iNOS)] by Western blot and reverse transcription-PCR analysis. Following DETA/NO treatment, APE/Ref-1 and other downstream molecules were induced. Knockdown of APE/Ref-1 or AP-1/JunD by specific small interfering RNA markedly reversed the induction by NO stress of target proteins. These results present evidence for the existence of a functional feedback loop contributing to progression and metastasis of melanoma cells. Resveratrol has been shown to be an APE/Ref-1 inhibitor and significant decreases in AP-1/JunD, MMP-1, Bcl-2, and iNOS protein levels occurred after exposure to resveratrol. This phenolic antioxidant may be an appropriate choice for combining with other compounds that develop resistance by up-regulation of these molecules.


Schwannoma on the nasal dorsum and tip with sensory changes.
Schwannomas, which originate from Schwann cells in the peripheral nervous system, are slowgrowing and uncommon benign tumors. Most schwannomas (90%) occur in isolation, and multiple occurrences are a characteristic feature of neurofibromas. Schwannomas of the nose and nasal tip are particularly unusual. Although a few cases of schwannomas of the sinusoidal tract and nasal septum have been reported, schwannomas arising from the nasal dorsum area and tip are extremely rare. Sensory abnormalities are also a very rare symptom. We excised a schwannoma on the nasal dorsum through direct incision and a schwannoma on the nasal tip through open rhinoplasty. No postoperative complications involving recurrence, hematoma, or infection occurred. The possibility of neurological changes should be considered in cases of an abnormality in the peripheral nervous system. Schwannoma must be kept in mind as a possible cause of neurological changes localized to a specific dermatome, and should always be considered in the differential diagnosis of a mass on the nose.


A schizophrenia locus may be located in region 10p15-p11.
In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.


The pancreatic β cell and type 1 diabetes: innocent bystander or active participant?
Type 1 diabetes mellitus (T1DM) is a chronic disease resulting from destruction of insulin-producing pancreatic β cells. Genetic and environmental factors contribute to T1DM onset. Use of high-throughput DNA sequencing has allowed geneticists to perform genome-wide association studies (GWAS) to identify novel gene loci associated with T1DM. Interestingly, >50% of these genes encode products that are expressed in β cells. These studies, coupled with emerging molecular evidence that β cells are impaired by gain-of-function or loss-of-function of these loci, suggest an active role for the β cell in eliciting its own demise. Although immune dysregulation plays a vital role in T1DM pathogenesis, understanding the mechanisms contributing to β cell failure may lead to new strategies to preserve or improve β cell function in patients with T1DM.


Antimicrobial resistance: an overview.
Increased antimicrobial resistance in bacteria that are important pathogens of humans, and spread of resistance from the closed environment of hospitals into open communities are increasingly perceived as a threat to public health. Any antimicrobial use, whether in humans, animals, plants or food processing technology, could lead to bacterial resistance. Use of antimicrobials in livestock production is suspected to significantly contribute to this phenomenon in species of bacteria which are common to humans and animals. Further research is required into the specific use conditions that govern the selection and dissemination of resistant bacteria. International travel and trade in animals and food increase the risks of antimicrobial resistance world-wide. Countries are considering import restrictions for products deemed a risk to public health. The Office International des Epizooties, a World Trade Organization reference organisation for the Agreement on the Application of Sanitary and Phytosanitary Measures, develops international standards on antimicrobial resistance which, as is the case for national measures, must be based on risk analysis. The scientific background and problems of resistance in human medicine are reviewed. Current knowledge, missing information and actions to be taken are identified.


Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity.
Major long-term complications in patients with diabetes are related to oxidative stress, caused by the hyperglycaemia characteristic for diabetes mellitus. The anti-oxidant coenzyme Q10 (CoQ10) has therefore been proposed as a beneficial supplement to diabetes treatment. Apart from its anti-oxidative function, CoQ10 appears to modulate immune functions by largely unknown mechanisms. The aim of this study was therefore to investigate the effect of CoQ10 on antimicrobial peptides and natural killer (NK) cells, both innate immune components implicated in the pathogenesis of diabetes and diabetes-associated long-term complications such as cardiovascular disease. We determined serum levels of antimicrobial peptides and the phenotype of NK cells isolated from peripheral blood of patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and from healthy controls. In addition, the same parameters were determined in diabetic patients after a 12-week period of CoQ10 supplementation. Two antimicrobial peptides, the human cathelicidin antimicrobial peptide (CAMP) and the human beta defensin 1 (hBD1), were reduced in serum from patients with T1DM. This defect was not reversible by CoQ10 supplementation. In contrast, CoQ10 reduced the levels of circulating hBD2 in these patients and induced changes in subset distribution and activation markers in peripheral NK cells. The results of the present study open up novel approaches in the prevention of long-term complications associated to T1DM, although further investigations are needed.


Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up.
The role of risk stratification in normotensive patients with acute pulmonary embolism (PE) is still unclear. We evaluated, in these patients, the usefulness of six prognostic markers for predicting in-hospital adverse events related to PE and 3-month mortality. Two hundred and one consecutive patients with confirmed acute PE and normal blood pressure, who were administered conventional anticoagulation, were recruited in a multicentre prospective cohort study with 3 months of follow-up. At baseline, they received a comprehensive risk-evaluation including echocardiographic assessment of right ventricular dysfunction, determination of troponin I, brain natriuretic peptide and D-dimer, arterial blood gas analysis and a clinical score. Primary outcome of the study was PE-related in-hospital death or clinical deterioration. Secondary outcomes were in-hospital and 3-month all-cause mortality. The primary outcome occurred in one patient (0.5%), who died from PE during hospitalization. The in-hospital and 3-month all-cause mortality were 2% and 9%, respectively. None of the prognostic markers was predictive of the primary outcome. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality (P = 0.02, 0.01 and < 0.01, respectively). Clinical score (HR, 4.7; 95% CI, 1.9-12.0), D-dimer (4.8; 1.4-16.3), hypoxemia (5.7; 2.1-15.1) and troponin I (7.5; 2.5-22.7) were predictors of 3-month all-cause mortality on univariate analysis. On multivariate analysis clinical score and troponin I remained independently predictive. We did not find prognostic markers useful as predictors of in-hospital PE-related adverse events. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality. Clinical score and troponin I independently predicted 3-month all-cause mortality.


Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies.
Tandem mass spectrometry (MS/MS) has been introduced in several newborn screening programs for the detection of a large number of inborn errors of metabolism, including fatty acid oxidation disorders (FAOD). Early identification and treatment of FAOD have the potential to improve outcome and may be life-saving in some cases; an estimated 5% of sudden infant deaths are attributable to undiagnosed disorders of fatty acid oxidation. We report very early neonatal presentations of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (TFP) deficiencies confirmed by molecular analysis. Both patients had cardiorespiratory collapse and hypoglycemia, without a history of maternal pregnancy complications. Retrospective MS/MS analysis of the original newborn screening blood spots revealed characteristic acylcarnitine profiles. These cases are among the earliest reported presentations of LCHAD and TFP deficiencies and further illustrate the potential of MS/MS as a valuable tool for newborn screening of FAOD. However, timely analysis and reporting of results to clinicians are essential, because these disorders can manifest in the first few days of life.


[The effect of hormones regulating calcium metabolism on the growth and metastasis of experimental tumors].
Injection of parathormone and thyrocalcitonin into rats with DMBA induced sarcomas resulted in a considerable stimulation of the metastasization process. It was found that the level of total Ca++ in tumor tissue was reduced under the influence of PTH. Under conditions of chronic exogenous hyperparathyroidism autoimmunereactions were suppressed. A prolonged administration of TCT did not alter considerable the total Ca++ content in tumor and markedly activated the autoantibody production in immunocompetent cells.


Prediction of cadmium (Cd) toxicity in cattle.
Hepato- and nephrotoxicity can be induced by the exposure to cadmium (Cd). This toxicity can be detected by the elevation of blood biomarkers such as ALT AST, ALP BUN and creatinine. These elevations are found in small animals, e.g. mice and rats. However the alteration of biomarkers did not investigate in large animals, e.g. cattle. Hepato- and nephrotoxicity induced by cadmium can also be examined by the alterations of metallothionein (MT) and metal transcription factor-1 (MTF-1). To present study the expressions of these markers, the cattle were classified into five groups according to the levels of cadmium in the kidneys. ALT, AST andALP were analyzed to determine liver damage whereas BUN and creatinine were examined for kidney damage. The results showed that blood biomarkers were not sensitive enough to be correlated markers to cadmium induced hepato- and nephrotoxicity in cattle. The expressions of MT and MTF-1 protein were investigated by immunofluorescence method. The expressions of MT and MTF-1 proteins were firstly found in the cattle group which had low cadmium concentration in tissues (< 0.5 mg/kg). Thus, these proteins could be used as the sensitive markers to determine the cadmium exposure. The MT and MTF-1 gene expressions were also studied. However, there was no correlation between the level of RNA and the protein expressions due to the concentration of protein levels bearing unclear relationship with the mRNA level. The investigation of these protein expressions is very useful because the result can be used as a protective method to prevent consumption of cadmium-contaminated beef.


The stimulant challenge test in depression.
The psychostimulants remain controversial agents for the diagnosis and treatment of depression. One promising area of investigation involves the use of a brief trial of a stimulant to predict patient response to subsequent treatment with a tricyclic antidepressant. Five of 10 studies have demonstrated the predictive value of the stimulant challenge test in depression; however, these studies have varied significantly in method. Studies in which oral doses of stimulant were given over an extended time have demonstrated greater predictive value than studies using a single intravenous challenge dose. Additional factors which differ between studies and may affect the predictive value of the stimulant challenge test are identified. The literature on the neuroendocrine responses to stimulant administration, direct stimulant effects on mood and activity, and stimulant neurotransmitter effects is summarized to further understanding of stimulant action in relation to affective disorders.


Characterization of hydrocarbons, halocarbons and carbonyls in the atmosphere of Hong Kong.
Ambient air quality measurements of 156 species including 39 alkanes, 32 alkenes, 2 alkynes, 24 aromatic hydrocarbons, 43 halocarbons and 16 carbonyls, were carried out for 120 air samples collected at two sampling stations (CW and TW) in 2001 throughout Hong Kong. Spatial variations of volatile organic compounds (VOCs) in the atmosphere were investigated. Levels of most alkanes and alkenes at TW site were higher than that at the CW site, while the BTEX concentrations at the two sites were close. The BTEX ratios at CW and TW were 1.6:10.1:1.0:1.6 and 2.1:10.8:1.0:2.0, respectively. For major halogenated hydrocarbons, the mean concentrations of chloromethane, CFCs 12 and 22 did not show spatial variations at the two sites. However, site-specific differences were observed for trichloroethene and tetrachloroethene. Furthermore, there were no significant differences for carbonyls such as formaldehyde, acetaldehyde and acetone between the two sites. The levels of selected hydrocarbons in winter were 1-5 times that in summer. There were no common seasonal trends for carbonyls in Hong Kong. The ambient level of formaldehyde, the most abundant carbonyl, was higher in summer. However, levels of acetaldehyde, acetone and benzaldehyde in winter were 1.6-3.8 times that in summer. The levels of CFCs 11 and 12, and chloromethane in summer were higher than that in winter. Strong correlation of most hydrocarbons with propene and n-butane suggested that the primary contributors of hydrocarbons were vehicular emissions in Hong Kong. In addition, gasoline evaporation, use of solvents, leakage of liquefied petroleum gas (LPG), natural gas leakage and other industrial emissions, and even biogenic emissions affected the ambient levels of hydrocarbons. The sources of halocarbons were mainly materials used in industrial processes and as solvents. Correlation analysis suggested that photochemical reactions made significant contributions to the ambient levels of carbonyls in summer whereas in winter motor vehicle emissions would be the major sources of the carbonyls. The photochemical reactivity of selected VOCs was estimated in this study. The largest contributors to ozone formation were formaldehyde, toluene, propene, m,p-xylene, acetaldehyde, 1-butene/i-butene, isoprene and n-butane, suggesting that motor vehicles, gasoline evaporation, use of solvents, leakage of LPG, photochemical processes and biogenic emission are sources in the production of ozone. On the other hand, VOCs from vehicles and gasoline evaporation were predominant with respect to reactions with OH radical.


Identification of mutations in Caenorhabditis elegans that cause resistance to high levels of dietary zinc and analysis using a genomewide map of single nucleotide polymorphisms scored by pyrosequencing.
Zinc plays many critical roles in biological systems: zinc bound to proteins has structural and catalytic functions, and zinc is proposed to act as a signaling molecule. Because zinc deficiency and excess result in toxicity, animals have evolved sophisticated mechanisms for zinc metabolism and homeostasis. However, these mechanisms remain poorly defined. To identify genes involved in zinc metabolism, we conducted a forward genetic screen for chemically induced mutations that cause Caenorhabditis elegans to be resistant to high levels of dietary zinc. Nineteen mutations that confer significant resistance to supplemental dietary zinc were identified. To determine the map positions of these mutations, we developed a genomewide map of single nucleotide polymorphisms (SNPs) that can be scored by the high-throughput method of DNA pyrosequencing. This map was used to determine the approximate chromosomal position of each mutation, and the accuracy of this approach was verified by conducting three-factor mapping experiments with mutations that cause visible phenotypes. This is a generally applicable mapping approach that can be used to position a wide variety of C. elegans mutations. The mapping experiments demonstrate that the 19 mutations identify at least three genes that, when mutated, confer resistance to toxicity caused by supplemental dietary zinc. These genes are likely to be involved in zinc metabolism, and the analysis of these genes will provide insights into mechanisms of excess zinc toxicity.


Effect of invasive EEG monitoring on cognitive outcome after left temporal lobe epilepsy surgery.
The objective of this cohort study was to compare neuropsychological outcomes following left temporal lobe resection (TLR) in patients with epilepsy who had or had not undergone prior invasive monitoring. Data were obtained from an institutional review board-approved, neuropsychology registry for patients who underwent epilepsy surgery at Cleveland Clinic between 1997 and 2013. A total of 176 patients (45 with and 131 without invasive EEG) met inclusion criteria. Primary outcome measures were verbal memory and language scores. Other cognitive outcomes were also examined. Outcomes were assessed using difference in scores from before to after surgery and by presence/absence of clinically meaningful decline using reliable change indices (RCIs). Effect of invasive EEG on cognitive outcomes was estimated using weighting and propensity score adjustment to account for differences in baseline characteristics. Linear and logistic regression models compared surgical groups on all cognitive outcomes. Patients with invasive monitoring showed greater declines in confrontation naming; however, when RCIs were used to assess clinically meaningful change, there was no significant treatment effect on naming performance. No difference in verbal memory was observed, regardless of how the outcome was measured. In secondary outcomes, patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using RCIs to define change. There were no outcome differences on other cognitive measures. Results suggest that invasive EEG monitoring conducted prior to left TLR is not associated with greater cognitive morbidity than left TLR alone. This information is important when counseling patients regarding cognitive risks associated with this elective surgery.


Ferritin nanocages: a novel platform for biomedical applications.
Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in living organism and thereby protects the cell from oxidative damage. The ferritin protein cages have been used as a reaction vessel for the synthesis of various non-native metallic nanoparticles inside its core and also used as a nanocarrier for various applications. Lack of suitable non-viral carrier for targeted delivery of anticancer drugs and imaging agents is the major problem in cancer therapy and diagnosis. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Recent studies, further establishes ferritin as a multifunctional nanocarrier for targeted cancer diagnosis and therapy. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. This review mainly focuses on the application of ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it also highlights various biomedical applications of ferritin nanocages.


Reconciling food production and biodiversity conservation: land sharing and land sparing compared.
The question of how to meet rising food demand at the least cost to biodiversity requires the evaluation of two contrasting alternatives: land sharing, which integrates both objectives on the same land; and land sparing, in which high-yield farming is combined with protecting natural habitats from conversion to agriculture. To test these alternatives, we compared crop yields and densities of bird and tree species across gradients of agricultural intensity in southwest Ghana and northern India. More species were negatively affected by agriculture than benefited from it, particularly among species with small global ranges. For both taxa in both countries, land sparing is a more promising strategy for minimizing negative impacts of food production, at both current and anticipated future levels of production.