Proton magnetic resonance spectroscopy of musculoskeletal lesions at 3 T with metabolite quantification.
To evaluate whether proton MR spectroscopy (MRS) at 3 T with metabolite quantification is helpful for characterizing musculoskeletal lesions and to reveal whether the concentration of choline is correlated with the pathologic degree of malignancy. Three-tesla MR images and proton MRS data from 27 consecutive patients with surgically proven musculoskeletal lesions were retrospectively analyzed. We analyzed the presence of choline peaks of malignant tumors according to the degree of malignancies, and we compared them with those of benign lesions. The concentrations of choline calculated by means of the linear combination of model spectra were also compared with respect to the degree of malignancy in each group. The proton MRS had an overall sensitivity of 68.4%, specificity of 87.5%, positive predictive value of 92.3%, and negative predictive value of 53.8% for the detection of choline compounds. The positive detection rate for choline compounds in the primary malignancy group (53.8%) was lower than that of the metastasis group (100%). All false-negative results were shown in the Grade 1 primary malignancy group. There was no difference in the concentration of choline compounds with respect to the pathologic degree of differentiation. MR spectroscopy at 3 T with metabolite quantification is a helpful method that shows high specificity (87.5%) in characterizing musculoskeletal lesions, even though its sensitivity (68.4%) is relatively low. Grade 1 primary malignancies of bone and soft tissue tumor have a high potential for producing false-negative results.


Concentrations of organochlorines related to titers to Epstein-Barr virus early antigen IgG as risk factors for hairy cell leukemia.
Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy that, according to modern classifications, is a subgroup of non-Hodgkin lymphomas (NHLs). A rapid increase in incidence of NHL has been reported in many countries. The reasons for this increase are largely unknown, but exposure to organochlorines has been suggested as a risk factor. Epstein-Barr virus is a human herpesvirus that has been associated with certain subgroups of NHL. In this study, we measured lipid adjusted blood concentrations (in nanogram per gram) of 36 congeners of polychlorinated biphenyls (PCBs), p, p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and four subgroups of chlordanes (trans-nonachlor, cis-nonachlor, MC6, and oxychlordane) in incident cases of HCL and controls from the general population. We obtained results on organochlorines and antibodies for 54 cases and 54 controls. Titers of antibodies to the Epstein-Barr early antigen and Epstein-Barr nuclear antigen, measured as P107, were correlated to concentrations of organochlorines to evaluate the possibility of an interaction between these factors in the pathogenesis of HCL. We found no significant difference in lipid-adjusted blood concentrations of total PCBs, p,p'-DDE, HCB, or the sum of the chlordanes between cases and controls. Titers of antibodies to Epstein-Barr early antigen IgG [Greater and equal to] 40 were correlated to an increased risk for HCL. This risk was further increased in those with a level above the median value of p,p'-DDE, HCB, or the sum of the chlordanes, suggesting an interaction between Epstein-Barr virus and a higher concentration of these chemicals. We also found increased risk for the sum of immunotoxic PCB group.


[The endocannabinoid system and its possible role in neurobiology of psychiatric disorders].
In the last years, numerous researches led to identify endocannabinoid system, a sophisticated short-range signaling system which is located both in Central Nervous System (CNS) and in whole organism. Because of its flexibility of expression, it plays a modulatory role in controlling the answers to stimuli which disturb homeostasis. On one hand it lets them occur whilst on the other it limits them in order to protect organism from consequences due to excessive reaction. In the CNS, endocannabinoid system is able to control the release of several neurotransmitters thanks to its retrograde signaling, modulating synaptic activity. Analysing this property during preclinical studies, it came out that the endocannabinoid system is involved in numerous physiologic processes, such as neuroendocrine axes, food consumption, brain reward and satisfaction mechanisms, memories storing and extinction, emotions and neurodevelopment regulation. Such discoveries have led researchers to suppose and investigate an alteration of this system in the physiopathology of some psychiatric disorders such as anxiety disorder, depression, eating disorders, addiction and schizophrenia. Results of such studies on animal models show a possible involvement of this system and were quickly followed by clinical studies which seem to confirm it. These findings might open new scenarios for understanding the pathogenesis of several psychiatric disorders and, at same time, they show new prospects for their treatment.


14-3-3sigma expression as a prognostic marker in undifferentiated nasopharyngeal carcinoma.
In this study, we investigated the expression of 14-3-3sigma tumor suppressor gene in a panel of NPC cell lines, xenografts and primary tumors. Our objective was to determine the correlation between 14-3-3sigma expression and clinical outcome in NPC. We detected reduced 14-3-3sigma expression in 5/6 NPC tumor lines by quantitative RT-PCR and Western blotting. By immunohistochemical staining, significant down-regulation of 14-3-3sigma was also found in 26/72 (36.1%) primary tumors of NPC patients, who were treated with curative radiotherapy. Promoter methylation was confirmed in a subset of primary tumors by methylation-specific PCR analysis. Importantly, we demonstrated that 14-3-3sigma expression is significantly associated with both overall survival (OS) and cancer-specific survival (CSS), but not with the clinical staging of NPC patients. The low 14-3-3sigma expression was associated with improved overall (p=0.029) and cancer-specific survival (p=0.042) on univariate analysis. 14-3-3sigma expression and staging were also independent variables to all the prognostic factors under multivariate analysis. In conclusion, low expression of 14-3-3sigma appears to be a valuable marker for better survival in patient with NPC. These results provide the evidence that 14-3-3sigma expression is a significant prognostic factor for NPC patients.


Psychological barriers.
Type 2 diabetes treatment outcomes ultimately depend on patients and their ability to make long-term behavioural changes that support good self-care and metabolic control. Patients' perceptions about diabetes and diabetes-related complications can have a strong influence on their emotional well-being, as well as day-to-day self-care and the quality of metabolic control. The gravity of diabetes is often underestimated, and many patients do not understand the link between poor glycaemic control and long-term complications of the disease. Similarly, people with diabetes commonly undervalue the role of lifestyle changes and pharmacological therapy in preventing future complications. Negative emotions and preconceptions about treatment can also discourage adherence to treatment plans. 'Psychological insulin resistance' caused by fear and concerns about insulin and daily insulin injections can discourage many patients from starting insulin therapy, even if oral agents have failed. Depression, stress and anxiety represent further obstacles to optimum self-care and the attainment of glucose goals. Healthcare professionals should endeavour to understand and accommodate these issues when setting personal treatment goals and developing plans to achieve them. Importantly, the advice and support they provide should be tailored to the unique needs of each patient. There is scope to improve outpatient consultations to ensure agreement between patients and professionals concerning issues discussed and decisions made, and this may help to improve recall and motivation to manage diabetes. Engaging patients in the goal-setting process can help to overcome potential barriers to good self-care and may increase the probability that treatment goals are achieved.


[Suppresion of the R-factor transduction transmission of antibiotic resistance markers in E. coli by distamycin A].
Some mechanisms of inhibition by distamycin A of transduction of antibiotic resistance markers of R-factors (RI drd and R222) with the moderate phage PI kc in E. coli were studied. The kinetics of the transduction of the R-factor markers was investigated in comparison with the stages of interaction of PI kc phage particles with bacterial cells of E. coli K-12 carrying the R-factors such as RI and R222 -- phage PI kc -- E. coli C6000. Later the effect of distamycin A on transduction of the above R-factors was studied using the same system. It was shown that distamycin A in concentrations of 75 gamma/ml suppressed the transduction of the R-markers when added to the transduction mixture simultaneously with the phage. The transduction rate decreased 15 times if the drug was added 5 minutes after beginning of the phage contact with the recipient culture. Addition of distamycin A at the 20th minute of the experiment induced no inhibition of the transduction of the R-factor markers. Preliminary 18-hour exposure to distamycin A of the recipient culture and phagolysates possessing transduction capacity resulted in decreased rates of the transduction of the antibiotic resistance markers 35 to 40 times. No inhibitory effect of distamycin A on the process of phenotypic manifestation of the antibiotic resistance markers of the R-factors was noted. The experiments showed that distamycin A affected the early stages of interaction of the transducing particles with the recipient culture, possibly the process of penetration of the transducing DNA of the R-factors into the cells of the recipient culture.


Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread.
The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.


Oscillating Gradient Diffusion-Weighted MRI for Risk Stratification of Uterine Endometrial Cancer.
Oscillating gradient diffusion-weighted imaging (DWI) enables elucidation of microstructural characteristics in cancers; however, there are limited data to evaluate its utility in patients with endometrial cancer. To investigate the utility of oscillating gradient DWI for risk stratification in patients with uterine endometrial cancer compared with conventional pulsed gradient DWI. Retrospective. Sixty-three women (mean age: 58 [range: 32-85] years) with endometrial cancer. 3 T MRI including DWI using oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) research sequences. Mean value of the apparent diffusion coefficient (ADC) values for OGSE (ADCOGSE ) and PGSE (ADCPGSE ) as well as the ADC ratio (ADCOGSE /ADCPGSE ) within endometrial cancer were measured using regions of interest. Prognostic factors (histological grade, deep myometrial invasion, lymphovascular invasion, International Federation of Gynecology and Obstetrics [FIGO] stage, and prognostic risk classification) were tabulated. Interobserver agreement was analyzed by calculating the intraclass correlation coefficient. The associations of ADCOGSE , ADCPGSE , and ADCOGSE /ADCPGSE with prognostic factors were examined using the Kendall rank correlation coefficient, Mann-Whitney U test, and receiver operating characteristic (ROC) curve. A P value of <0.05 was statistically significant. Compared with ADCOGSE and ADCPGSE , ADCOGSE /ADCPGSE was significantly and strongly correlated with histological grade (observer 1, τ = 0.563; observer 2, τ = 0.456), FIGO stage (observer 1, τ = 0.354; observer 2, τ = 0.324), and prognostic risk classification (observer 1, τ = 0.456; observer 2, τ = 0.385). The area under the ROC curves of ADCOGSE /ADCPGSE for histological grade (observer 1, 0.92, 95% confidence intervals [CIs]: 0.83-0.98; observer 2, 0.84, 95% CI: 0.73-0.92) and prognostic risk (observer 1, 0.80, 95% CI: 0.68-0.89; observer 2, 0.76, 95% CI: 0.63-0.86) were significantly higher than that of ADCOGSE and ADCPGSE . The ADC ratio obtained via oscillating gradient and pulsed gradient DWIs might be useful imaging biomarkers for risk stratification in patients with endometrial cancer. 3 TECHNICAL EFFICACY: Stage 2.


Expression of an HCV core antigen coding gene in tobacco (N. tabacum L.).
Hepatitis C virus (HCV) is the major agent causing chronic liver disease. The core gene is the most conserved sequence in the HCV genome and proved immunoreactive when expressed in bacteria and antigenic in humans. In order to test the ability of plants to express the core gene for the production of core antigen, transgenic tobacco plants carrying the core gene were generated. The core protein was stably synthesized in T(0) and T(1) generations and was found to be immunoreactive, not only with anti-core polyclonal and monoclonal antibodies, but also was able to recognize the HCV virus in infected human serum. The prospects of producing a plant based vaccine and/or a food vaccine for this important virus are discussed.


Power of quantitative trait locus mapping for polygenic binary traits using generalized and regression interval mapping in multi-family half-sib designs.
A generalized interval mapping (GIM) method to map quantitative trait loci (QTL) for binary polygenic traits in a multi-family half-sib design is developed based on threshold theory and implemented using a Newton-Raphson algorithm. Statistical power and bias of QTL mapping for binary traits by GIM is compared with linear regression interval mapping (RIM) using simulation. Data on 20 paternal half-sib families were simulated with two genetic markers that bracketed an additive QTL. Data simulated and analysed were: (1) data on the underlying normally distributed liability (NDL) scale, (2) binary data created by truncating NDL data based on three thresholds yielding data sets with three different incidences, and (3) NDL data with polygenic and QTL effects reduced by a proportion equal to the ratio of the heritabilities on the binary versus NDL scale (reduced-NDL). Binary data were simulated with and without systematic environmental (herd) effects in an unbalanced design. GIM and RIM gave similar power to detect the QTL and similar estimates of QTL location, effects and variances. Presence of fixed effects caused differences in bias between RIM and GIM, where GIM showed smaller bias which was affected less by incidence. The original NDL data had higher power and lower bias in QTL parameter estimates than binary and reduced-NDL data. RIM for reduced-NDL and binary data gave similar power and estimates of QTL parameters, indicating that the impact of the binary nature of data on QTL analysis is equivalent to its impact on heritability.


The Impact of Pandemic-Related Restrictions on Dementia Risk Factors in Older Adults.
Adults aged 65+ are at highest risk for severe COVID-19 outcomes, and prior to the distribution of vaccines in the U.S., were strongly advised to quarantine at home to reduce risk of infection. This study examines how COVID-19 restrictions impacted various dementia risk factors and social determinants of health among older adults. Data came from the Systematic Multi-Domain Alzheimer's Risk Reduction Trial, a randomized controlled trial of a multi-domain intervention in higher-risk older adults (aged 70-89). A questionnaire was administered to participants (n = 156; 90.7% response rate) between May 2020 and March 2021. The data show a significant decline in social activity, physical activity, and mood among respondents. Compared to living with others, living alone was associated with worsened physical activity, diet, and subjective memory/thinking, adjusted for sex and age. These results suggest that the COVID-19 pandemic exacerbated several risk factors for dementia in older adults, particularly in those living alone.


[Damage connected with cocaine consumption: all we see is the tip of the iceberg].
According to the European Drug and Drug Addiction Observatory, after Cannabis, Cocaine is the most widely used illegal drug in Europe. Awareness of the damage caused by consuming this substance is clear in some areas, while in others it may be ignored, underestimated or poorly dimensioned. The information systems that do exist almost certainly underestimate the number of deaths connected with cocaine. Apart from the potential the drug has to cause direct damage to different organs of the body, its consumption can lead to serious problems arising from other circumstances that are not always connected with this drug, including murders, traffic accidents and accidents at work, infectious diseases related to high-risk behaviour, and suicides. Cocaine is increasingly present in cases of violence such as fights or aggression, in many cases accompanied by the use of knives and firearms. Serious behavioural disorders are being seen more and more frequently in the healthcare services, and in clinics we are witnessing a worrying increase on a day-to-day basis of conflictive episodes associated with the use of cocaine amongst our patients. This damage does not only affect a marginal population, but instead all levels of society, and often goes unnoticed or unreported. Coordination between different institutions and healthcare areas is essential in order to obtain this information, and in this way to provide a more precise picture of the consequences of Cocaine consumption, as today we are still far from having quantified its true dimension.


Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis.
The clinical syndromes of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are both characterized by dysregulated inflammation with prolonged fever, hepatosplenomegaly, coagulopathy, hematologic cytopenias, and evidence of hemophagocytosis in the bone marrow or liver. While HLH is either inherited or acquired, children with severe rheumatic diseases, most notably systemic juvenile idiopathic arthritis, are at risk for MAS. The phenotypic similarity between HLH and MAS raises the possibility that they share common pathogenetic mechanisms. Familial forms of HLH have been attributed to mutations in the genes encoding perforin (PRF1) and Munc13-4 (UNC13D), among others, and are characterized by defective cytotoxic lymphocyte function. While some patients with systemic JIA have decreased levels of perforin protein expression and natural killer (NK) cell function, mutations of HLH-associated genes in patients with systemic JIA have not been reported. We report the case of an 8-year-old girl with systemic JIA without MAS who was found to have compound heterozygous mutations of UNC13D and reduced NK cell cytotoxic function. This case broadens the range of clinical phenotypes attributable to UNC13D mutations and offers new insights into the etiology and pathogenesis of systemic JIA.


The Effects of Neck-Specific Training Versus Prescribed Physical Activity on Pain and Disability in Patients With Cervical Radiculopathy: A Randomized Controlled Trial.
To compare the effects of a neck-specific training program to prescribed physical activity with both groups receiving a cognitive behavioral approach, on pain and disability in patients with cervical radiculopathy (CR). Parallel-group randomized clinical trial with follow-up at 3, 6, 12, and 24 months. Recruitment and assessments of participants were performed at a university hospital. Interventions were performed in primary care setting at outpatient physiotherapy clinics. Patients (N=144) with CR were recruited to participate in this clinical trial. Patients were randomly assigned to 3 months of either of a neck-specific training program or prescribed physical activity. Primary outcomes included self-rated neck and arm pain as collected by the visual analog scale (VAS). Secondary outcomes were self-rated headache measured with the VAS, the Neck Disability Index, the EuroQol 5D, the Fear Avoidance Beliefs Questionnaire, and the Hospital Anxiety and Depression Scale. Assessments were performed at baseline and at 3-, 6-, 12-, and 24-month follow-up periods. Intention-to-treat and per-protocol analyses showed no significant interaction (group × time) or group effects. There were, however, significant time effects indicating improvement over time for both groups for all outcomes except for levels of depression. The study revealed that neck-specific training as well as prescribed physical activity both including additional cognitive behavioral approach decreased the pain in patients with CR, that is, participants improved regardless of the intervention received. There is a lack of consensus of how to best manage individuals with CR. However, our findings suggest that CR has a natural favorable long-term outcome when patients are prescribed neck-specific training and exercise in combination with a behavioral approach.


Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer.
TP53 status [mutations, immunostaining, and loss of heterozygosity (LOH)], expression of c-erbB-2, bcl-2, and histological grading were correlated to the response to doxorubicin monotherapy (14 mg/m2) administered weekly to 90 patients with locally advanced breast cancer. Mutations in the TP53 gene, in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3, respectively). Similarly, expression of c-erbB-2 (P = 0.041), a high histological grade (P = 0.023), and lack of expression of bcl-2 (P = 0.018) all predicted chemoresistance. No statistically significant association between either p53 immunostaining or TP53 LOH and response to therapy was recorded, despite the finding that both were associated with TP53 mutation status (p53 immunostaining, P < 0.001; LOH, P = 0.021). Lack of immunostaining for p53 despite mutation of the TP53 gene was particularly seen in tumors harboring nonsense mutations or deletions/splices (7 of 10 negative for staining compared with 4 of 16 with missense mutations). TP53 mutations (total/affecting L2/L3 domains) were associated with expression of c-erbB-2 (P < 0.001 for both), high histological grade (P = 0.001 and P = 0.025), and bcl-2 negativity (P = 0.003 and P = 0.002). TP53 mutations, histological grade, and expression of bcl-2 (but not LOH or c-erbB-2 expression) all predicted for relapse-free as well as breast cancer-specific survival in univariate analysis (Ps between <0.0001 and 0.0155), but only tumor grade was found to be predictive in multivariate analysis (P = 0.01 and P = 0.0007, respectively). Our data are consistent with the hypothesis that certain TP53 mutations predict for resistance to doxorubicin in breast cancer patients. However, the observation that the majority of patients with TP53 mutations affecting or disrupting the L2/L3 domains with LOH in addition (n = 12) obtained a partial response (n = 4) or stabilization of disease (n = 5) during chemotherapy suggests redundant mechanisms to compensate for loss of p53 function. Our findings are consistent with the hypothesis that other defects may act in concert with loss of p53 function, causing resistance to doxorubicin in breast cancers.


Expression of breast cancer resistance protein in blast cells from patients with acute leukemia.
Breast cancer resistance protein (BCRP) is a novel member of the adenosine triphosphate-binding cassette superfamily of transport proteins. Transfection and enforced expression of BCRP in drug-sensitive cells confer resistance to mitoxantrone, doxorubicin, daunorubicin, and topotecan. We studied blast cells from 21 acute leukemia patients (20 acute myeloid leukemia, 1 acute lymphocytic leukemia) for the expression of BCRP mRNA using a quantitative reverse-transcription polymerase chain reaction assay. BCRP mRNA expression varied more than 1000-fold among the samples tested, with low or barely detectable expression in half of the samples. Seven samples (33%) had relatively high expression of BCRP mRNA. High expression of BCRP did not correlate strongly with high expression of P-glycoprotein, suggesting that BCRP may cause resistance to certain antileukemic drugs in P-glycoprotein-negative cases. High expression of BCRP mRNA is sufficiently frequent in AML to warrant more extensive investigations to determine the relation of disease subtype and treatment outcome to BCRP expression and function.


[Antigenic differences in wild-type and guinea pig-adapted Ebola virus strains].
The splenocytes isolated from the mice immunized with wild-type or guinea pig-adapted Ebola virus strains were used to obtain hybridoma collections. Investigation of the monoclonal antibodies (mAb) obtained to one of the strains to another revealed antigenic interstrain differences in nucleoprotein and VP40. It is interesting that the differences were found in the hydridoma collection obtained against the wild-type strain. The mAbs produced by hydridomas to the adapted strain were found to equally well the antigens of both strains.


Principles for the regulation of multiple developmental pathways by a versatile transcriptional factor, BLIMP1.
Single transcription factors (TFs) regulate multiple developmental pathways, but the underlying mechanisms remain unclear. Here, we quantitatively characterized the genome-wide occupancy profiles of BLIMP1, a key transcriptional regulator for diverse developmental processes, during the development of three germ-layer derivatives (photoreceptor precursors, embryonic intestinal epithelium and plasmablasts) and the germ cell lineage (primordial germ cells). We identified BLIMP1-binding sites shared among multiple developmental processes, and such sites were highly occupied by BLIMP1 with a stringent recognition motif and were located predominantly in promoter proximities. A subset of bindings common to all the lineages exhibited a new, strong recognition sequence, a GGGAAA repeat. Paradoxically, however, the shared/common bindings had only a slight impact on the associated gene expression. In contrast, BLIMP1 occupied more distal sites in a cell type-specific manner; despite lower occupancy and flexible sequence recognitions, such bindings contributed effectively to the repression of the associated genes. Recognition motifs of other key TFs in BLIMP1-binding sites had little impact on the expression-level changes. These findings suggest that the shared/common sites might serve as potential reservoirs of BLIMP1 that functions at the specific sites, providing the foundation for a unified understanding of the genome regulation by BLIMP1, and, possibly, TFs in general.


The sxa2-dependent inactivation of the P-factor mating pheromone in the fission yeast Schizosaccharomyces pombe.
Haploid cells of the fission yeast Schizosaccharomyces pombe exist in one of two mating types, referred to as M and P. Conjugation occurs between cells of opposite mating type and is controlled by the reciprocal action of diffusible pheromones. Loss of function of the sxa2 gene in M cells causes hypersensitivity to the P-factor mating pheromone and a reduction in mating efficiency. Here we demonstrate the secretion of an sxa2-dependent carboxypeptidase that inactivates P-factor by removal of the C-terminal leucine residue.


Organic mulches reduce crop attack by sweetpotato weevil (Cylas formicarius).
Mulching with organic materials is a management practice with long history for weed suppression, soil water conservation and erosion control. Its potential impact on crop pests is less well explored. Here we report its utility for reducing crop damage by the serious pest, sweetpotato weevil (Cylas formicarius). Laboratory bioassays measured the response of adult female weevils to sweetpotato storage roots beneath mulches of fresh or dried plant materials. Weevils were significant repelled by fresh basil, catnip, basil lime and dry eucalyptus, cypress, lucerne and sugarcane. A subsequent field study found that mulches of dry cypress, eucalyptus and lucerne reduced movement of weevils from a release point to reach sweetpotato plants and lowered level of damage to storage roots. Results demonstrate that mulching with organic materials merits further testing as part of the integrated management of sweetpotato weevil, particularly to protect developing storage roots during dry periods when soil cracking can facilitate access by pests.


Home delivery and neonatal mortality in North Carolina.
Neonatal mortality examined by place and circumstances of delivery in North Carolina during 1974 through 1976 with attention given to home delivery. Planned home deliveries by lay-midwives resulted in three neonatal deaths per 1,000 live births; planned home deliveries without a lay-midwife, 30 neonatal deaths per 1,000 live births; and unplanned home deliveries, 120 neonatal deaths per 1,000 live births. The women babies were delivered by lay-midwives were screened in county health departments and found to be medically at low risk of complication, despite having demographic characteristics associated with high-risk of neonatal mortality. Conversely, the women delivered at home without known prenatal screening or a trained attendant had low-risk demographic characteristics but experienced a high rate of neonatal mortality. Planning, prenatal screening, and attendant-training were important in differentiating the risk of neonatal mortality in this uncontrolled, observational study.


[The ultrastructure of the ciliary epithelium in patients with the Zivert-Kartagener syndrome, bronchiectasis and cystic hypoplasia of the lungs].
Ultrastructure of the cilia of the bronchial epithelium was studied in 26 patients with Zivert-Kartagener syndrome, 12 patients with bronchiectasis and 10 patients with cystic lung hypoplasia. All changes of the cytolemma and cytoskeleton are found to be of a combined type. The degree of the bronchial inflammation was of the decisive influence on the state of the ciliary cells. Common features of the ultrastructural alterations are noted in the groups of patients compared. Ultrastructural defects characteristic for the patients with the Zivert-Kartagener triad were not found. It is concluded that all the ultrastructural defects of the ciliary epithelium were of the acquired character.


alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings.
The proteasomes have a central role in catalysing protein degradation among both prokaryotes and eukaryotes. The 20 S proteasome constitutes their catalytic core. In studying the structure of Trypanosoma brucei 20 S proteasomes, we isolated by two-dimensional (2D) gel electrophoresis a 27 kDa subunit protein with an estimated pI of 4.7 and subjected it to mass spectrometric analysis. A tryptic peptide sequence from the protein was found identical with that of the rat alpha5 subunit. With the use of antiserum against T. brucei 20 S proteasomes to screen a T. b. rhodesiense lambda expression cDNA library, we obtained a cDNA clone encoding a full-length protein of 246 amino acid residues with a calculated molecular mass of 27174 Da and a pI of 4.71. It bears 50. 0% and 46.3% sequence identity with rat and yeast proteasome subunit alpha5 respectively, and matches all the peptide sequences derived from MS of the 2D gel-purified protein. The protein is thus designated the alpha5 subunit of T. brucei 20 S proteasome (TbPSA5). The recombinant protein, expressed in plasmid-transformed Escherichia coli, was found in a 27 kDa monomer form as well as polymerized forms with estimated molecular masses ranging from 190 to 800 kDa. Under the electron microscope, the most highly polymerized forms bear the appearance of cylinders of four-stacked heptamer rings with an estimated outer diameter of 14.5 nm and a length of 18 nm, which were immunoprecipitable by anti-(T. brucei 20 S proteasome) antiserum. In view of the documented self-assembly of the archaeon proteasome alpha subunit into double heptamer rings and the spontaneous assembly of the two alpha subunits from the 20 S proteasome of Rhodococcus erythropolis, the self-assembly of the T. brucei alpha subunit might reflect a common feature of proteasome biogenesis shared by prokaryotes and primitive eukaryotes such as the trypanosomes but apparently lost among the higher forms of eukaryote such as the yeast and the mammals.


Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy.
Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation.


Engineering Cf /ZrB2 -SiC-Y2 O3 for Thermal Structures of Hypersonic Vehicles with Excellent Long-Term Ultrahigh Temperature Ablation Resistance.
Ultrahigh temperature ceramic matrix composites (UHTCMCs) are critical for the development of high Mach reusable hypersonic vehicles. Although various materials are utilized as the thermal components of hypersonic vehicles, it is still challenging to meet the ultrahigh temperature ablation-resistant and reusability. Herein, the Y2 O3 reinforced Cf /ZrB2 -SiC composites are designed, which demonstrates near-zero damage under long-term ablation at temperatures up to 2500 °C for ten cycles. Notably, the linear ablation rate of the composites (0.33 µm s-1 ) is over 24 times better than that of the conventional Cf /C-ZrC at 2500 °C (8.0 µm s-1 ). Moreover, the long-term multi-cycle ablation mechanisms of the composites are investigated with the assistance of DFT calculations. Especially, the size effect and the content of the Zr-based crystals in the oxide layer fundamentally affect the stability of the oxide layer and the ablation properties. The ideal component and structure of the oxide layer for multi-cycle ablation condition are put forward, which can be obtained by controlling the Y2 O3 /ZrB2 mole ratio and establishing Y-Si-O - t-Zr0.9 Y0.1 O1.95 core-shell nano structure. This work proposes a new strategy for improving the long-term multi-cycle ablation resistance of UHTCMCs.


Structure of the insect head as revealed by the EN protein pattern in developing embryos.
The structure of the insect head has long been a topic of enjoyable yet endless debate among entomologists. More recently geneticists and molecular biologists trying to better understand the structure of the head of the Dipteran Drosophila melanogaster have joined the discourse extrapolating from what they have learned about Drosophila to insects in general. Here we present the results of an investigation into the structure of the insect head as revealed by the distribution of engrailed related protein (Engrailed) in the insect orders Diptera, Siphonaptera, Orthoptera and Hemiptera. The results of this comparative embryology in conjunction with genetic experiments on Drosophila melanogaster lead us to conclude: (1) The insect head is composed of six Engrailed accumulating segments, four postoral and two preoral. The potential seventh and eighth segments (clypeus or labrum) do not accumulate Engrailed. (2) The structure known as the dorsal ridge is not specific to the Diptera but is homologous to structures found in other insect orders. (3) A part of this structure is a single segment-like entity composed of labial and maxillary segment derivatives which produce the most anterior cuticle capable of taking a dorsal fate. The segments anterior to the maxillary segment produce only ventral structures. (4) As in Drosophila, the process of segmentation of the insect head is fundamentally different from the process of segmentation in the trunk. (5) The pattern of Engrailed accumulation and its presumed role in the specification and development of head segments appears to be highly conserved while its role in other pattern formation events and tissue-specific expression is variable. An overview of the pattern of Engrailed accumulation in developing insect embryos provides a basis for discussion of the generality of the parasegment and the evolution of Engrailed patterns.


Condensation of the forespore nucleoid early in sporulation of Bacillus species.
Fluorescence microscopic examination coupled with digital videoimage analysis of 4',6-diamidino-2-phenylindole-stained sporulating cells of Bacillus megaterium or Bacillus subtilis revealed a striking condensation of the forespore nucleoid. While both mother cell and forespore compartments had equal amounts of DNA, the forespore nucleoid became greater than 2-fold more condensed than the mother cell nucleoid. The condensation of the forespore nucleoid began after only the first hour of sporulation, 2 to 3 h before expression of most forespore-specific genes including those for small, acid-soluble spore proteins, and was abolished in spo0 mutants but not in spoII or spoIII mutants. It is possible that this striking condensation of forespore DNA plays some role in modulating gene expression during sporulation.


Spinal interleukin-6 (IL-6) inhibits nociceptive transmission following neuropathy.
Interleukin-6 (IL-6) is a neuropoietic cytokine which is dramatically upregulated following peripheral nerve injury at the site of injury, in the dorsal root ganglion (DRG) and in the spinal cord. The functional effects of IL-6 in nociception in normal conditions and following nerve injury are unclear. Thus the aim of this study was to assess the effect of spinal IL-6 administration on nociceptive transmission in naive, sham-operated and neuropathic (spinal nerve ligation, SNL) rats using in vivo electrophysiology to elucidate the possible role of IL-6 in neuropathic pain. In anaesthetised rats, extracellular recordings were made from individual convergent dorsal horn neurones following electrical and natural (mechanical and thermal) stimulation of peripheral receptive fields. Exogenous spinal IL-6 (100-500 ng) had no significant effect on electrically evoked neuronal responses in naive rats. In contrast, following neuropathy, spinal IL-6 produced a dose-related inhibition of the electrically evoked C-fibre, initial C-fibre and measures of neuronal hyperexcitability (post discharge and wind-up). In addition, spinal IL-6 markedly inhibited mechanical neuronal responses in neuropathic rats. Higher doses of spinal IL-6 also inhibited, to a lesser degree, the initial C-fibre, post discharge and wind-up responses in sham-operated rats. These studies show that following nerve injury the actions of the cytokine alter so that spinal administration of IL-6 elicits anti-nociceptive effects not observed under normal conditions. Moreover, the inhibitory effects of IL-6 on C-fibre activity and neuronal hyperexcitability, suggest IL-6 to be a potential modulator of neuropathic pain.


Pharmacodynamics of levofloxacin and ciprofloxacin in a murine pneumonia model: peak concentration/MIC versus area under the curve/MIC ratios.
During the last decade some studies have shown that the area under the curve (AUC)/MIC ratio is the pharmacodynamic index that best predicts the efficacies of quinolones, while other studies suggest that the predictive value of the peak concentration/MIC (peak/MIC) ratio is superior to the AUC/MIC ratio in explaining clinical and microbiological outcomes. In classical fractionated dose-response studies with animals, it is difficult to differentiate between the AUC/MIC ratio and the peak/MIC ratio because of colinearity. Three different levofloxacin and ciprofloxacin dosing regimens were studied in a neutropenic mouse pneumonia model. The different regimens were used with the aim of increasing the AUC/MIC ratio without changing the peak/MIC ratio and vice versa. The first regimen (RC) consisted of daily doses of 5 up to 160 mg/kg of body weight divided into one, two, or four doses. In the second regimen (R0), mice were given 1.25 mg/kg every hour from 1 to 23 h, while the dose given at 0 h was 2.5, 5, 10, 20, 40, or 80 mg/kg. In the third regimen (R11), mice also received 1.25 mg/kg every hour from 0 to 23 h; but in addition, they also received 2.5, 5, 10, 20, 40, or 80 mg/kg at 11 h. The level of protein binding was also evaluated. The results indicate that the unbound fraction (f(u)) was concentration dependent for both levofloxacin and ciprofloxacin and ranged from approximately 0.67 to 0.88 for both drugs between concentrations of 0.5 and 80 mg/liter. The relationships between the AUC/MIC ratio and the number of CFU were slightly better than those between the peak/MIC ratio and the number of CFU. There was no clear relationship between the amount of time that the concentration remained above the MIC and effect (R(2) < 0.1). For both drugs, the peak/MIC ratio that resulted in a 50% effective concentration was lower for the R0 and R11 dosing regimens, indicating the importance of the AUC/MIC ratio. The same was true for the static doses. Survival studies showed that for mice treated with the low doses the rate of survival was comparable to that for the controls, but with the higher doses the rate of survival was better for mice receiving the R0 regimen. We conclude that for quinolones the AUC/MIC ratio best correlates with efficacy against pneumococci and that the effect of the peak/MIC ratio found in some studies could be partly explained by concentration-dependent protein binding.


Biotransformation of phenol to hydroquinone and catechol by rat liver microsomes.
Hepatic microsomal biotransformation of phenol to hydroquinone and catechol has been investigated with special reference to the covalent binding to microsomal protein of reactive metabolites formed during microsomal metabolism of phenol. Incubation of [14C]phenol with microsomes from phenobarbital-treated rat liver in the presence of an NADPH-generating system resulted in the formation of hydroquinone and catechol in the ratio of 20:1. No significant formation of 1,2,4-benzenetriol was observed. The biotransformation of phenol to both hydroquinone and catechol required NADPH and molecular oxygen. NADH was much less effective than NADPH as an electron donor and exhibited no significant synergistic effect when used together with NADPH. The biotransformation was inhibited by typical cytochrome P-450 inhibitors such as carbon monoxide, SKF 525-A, and metyrapone. These results indicated the involvement of cytochrome P-450 in the microsomal hydroxylation of phenol at both the ortho- and para-positions. Covalent binding of radioactivity to microsomal protein was observed when [14C]phenol was incubated with rat liver microsomes in the presence of an NADPH-generating system. The covalent binding was also found to require NADPH and molecular oxygen. Inclusion of cytochrome P-450 inhibitors in the incubation mixture resulted in a decrease in the covalent binding. These results indicated that at least one step in the metabolic activation of phenol to the metabolites responsible for covalent binding to microsomal protein was mediated by cytochrome P-450. Inclusion of N-acetylcysteine in the incubation mixture resulted in the complete inhibition of the covalent binding of radioactivity derived from [14C]phenol to microsomal protein, and there was a concomitant formation of N-acetylcysteine adducts of hydroquinone and catechol. These results indicated that hydroquinone and catechol were both precursors to reactive metabolites responsible for the covalent binding.


The Swedish Longitudinal Gambling Study (Swelogs): design and methods of the epidemiological (EP-) track.
Swelogs (Swedish Longitudinal Gambling Study) epidemiological (EP-) track is a prospective study with four waves of data-collection among Swedish citizens aged 16-84 years at baseline. The major objectives of this track are to provide general population estimates of the prevalence and incidence of problem and at-risk gambling and enable comparisons with the first Swedish national study on gambling and problem gambling (Swegs) conducted in 1997/1998. The overall study (Swelogs) comprises three tracks of data collection; one epidemiological, one in-depth and one follow-up. It is expected to provide information that will inform the development of evidence-based methods and strategies to prevent the development of gambling problems. This paper gives an overview of the design of the epidemiological track, especially of its two first waves. The baseline wave, performed between October 2008 and August 2009, included 8165 subjects, of whom 6021 were re-assessed one year later. A stratified random sampling procedure was applied. Computer-supported telephone interviews were used as the primary method. Postal questionnaires were used to follow-up those not reached by telephone. The response rate was 55% in the first wave and 74% in the second. The interview and questionnaire data are supplemented by register data.


Durability and flexibility of chimpanzee grooming patterns during a period of dominance instability.
Growing evidence from studies on primates and other taxa has shown that the maintenance of long-term affiliative patterns influences fitness. Thus, understanding how individuals regulate social interactions in response to environmental and social factors contributes to our understanding of the evolutionary basis of sociality. We investigated the durability of affiliation patterns in chimpanzees across three 3-month periods of varying social uncertainty depending on the degree of stability in the male hierarchy, with a 2-year gap between each period. Periods were unstable (no clear alpha male), recently stable (new alpha male just established) and stable (alpha male in place for 2 years). We focused on three features of social exchange shared by human and non-human primates: consistency of exchanges across periods, durability of preferred partners, and degree of reciprocity in each period. We compared male-to-male, female-to-female, male-to-female, and female-to-male grooming patterns. Overall, more grooming was exchanged in the stable period. Grooming patterns were not consistent across the three periods, but were only consistent between the recently stable and stable periods for female-to-female and male-to-female dyads. As predicted from the opportunistic nature of male relationships, male-to-male grooming was least likely to be correlated across all periods and males had relatively fewer durable (i.e., preferred partners in all periods) same-sex partners than females. Our predictions that grooming reciprocity would be less likely during the unstable period and in male-male dyads were only partially supported. We found grooming reciprocity in all periods for female-female dyads but only in the stable period for male-male and female-male dyads. Although long-term affiliative patterns are well studied in primates, this is the first study to investigate the association between social uncertainty and durability of affiliative patterns. Our findings suggest social uncertainty influences social exchange and highlight the importance of considering group instability in studies of social relationships.


Synergy of cell-cell repulsion and vacuolation in a computational model of lumen formation.
A key step in blood vessel development (angiogenesis) is lumen formation: the hollowing of vessels for blood perfusion. Two alternative lumen formation mechanisms are suggested to function in different types of blood vessels. The vacuolation mechanism is suggested for lumen formation in small vessels by coalescence of intracellular vacuoles, a view that was extended to extracellular lumen formation by exocytosis of vacuoles. The cell-cell repulsion mechanism is suggested to initiate extracellular lumen formation in large vessels by active repulsion of adjacent cells, and active cell shape changes extend the lumen. We used an agent-based computer model, based on the cellular Potts model, to compare and study both mechanisms separately and combined. An extensive sensitivity analysis shows that each of the mechanisms on its own can produce lumens in a narrow region of parameter space. However, combining both mechanisms makes lumen formation much more robust to the values of the parameters, suggesting that the mechanisms may work synergistically and operate in parallel, rather than in different vessel types.


New trends in personalized treatment of depression.
Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades "a trial and error" approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD. In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions. Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.


Deformation of confined liquid interfaces by inhomogeneous electric fields and localized particle forces.
Oil-water interfaces that are created by confining a certain amount of oil in a square shaped pixel (∼200 x 200 μm2 with a height of ∼10 μm) topped by a layer of water, have a curvature that depends on the amount of oil that happens to be present in the confining area. Under the application of an electric field normal to the interface, the interface will deform due to inhomogeneities in the electric field. These inhomogeneities are expected to arise from the initial curvature of the meniscus, from fringe fields that emerge at the confining pixel walls and, if applicable, from interfacially adsorbed particles. We model the shape of the confined oil-water interface invoking capillarity and electrostatics. Furthermore, we measure the initial curvature by tracking the position of interfacially adsorbed particles depending on sample tilt. We found that the pixels exhibited meniscus curvature radii ranging from 0.6-7 mm. The corresponding model based minimum oil film thicknesses range between 0.7 and 9 μm. Furthermore, the model shows that the initial meniscus curvature can increase up to 76 percent relative to the initial curvature by the electric field before the oil film becomes unstable. The pixel wall and particles are shown to have minimal impact on the interface deformation.


Specific detection of oxytetracycline using DNA aptamer-immobilized interdigitated array electrode chip.
An electrochemical sensing system for oxytetracycline (OTC) detection was developed using ssDNA aptamer immobilized on gold interdigitated array (IDA) electrode chip. A highly specific ssDNA aptamer that bind to OTC with high affinity was employed to discriminate other tetracyclines (TCs), such as doxycycline (DOX) and tetracycline (TET). The immobilized thiol-modified aptamer on gold electrode chip served as a biorecognition element for the target molecules and the electrochemical signals generated from interactions between the aptamers and the target molecules was evaluated by cyclic voltammetry (CV) and square wave voltammetry (SWV). The current decrease due to the interference of bound OTC, DOX or TET was analyzed with the electron flow produced by a redox reaction between ferro- and ferricyanide. The specificity of developed EC-biosensor for OTC was highly distinguishable from the structurally similar antibiotics (DOX and TET). The dynamic range was determined to be 1-100 nM of OTC concentration in semi-logarithmic coordinates.


Neighborhood disadvantage and children's cognitive skill trajectories.
This study examined how neighborhood poverty is associated with children's trajectories of growth in math and reading skills in early elementary school, and how these associations vary by student characteristics, using multilevel growth models with nationally representative data from the 2011 Early Childhood Longitudinal Study-Kindergarten Cohort. About one-quarter (25.6%) of children lived in communities of concentrated poverty. Findings suggest that achievement gaps by neighborhood disadvantage are large and present before Kindergarten, shrink during the Kindergarten year, but then widen the year following, and remain relatively consistent in the first years of elementary school. Growth in math skills appeared to vary more with neighborhood poverty than growth in reading skills. There was limited evidence that the relationship between neighborhood poverty and test score trajectories varied by child race, ethnicity, early education and Kindergarten experience, and parents' immigration status, but growth differences across student characteristics were small. Policy and research implications are discussed.


Clinical features of irreversible rejection after allogeneic uterus transplantation in cynomolgus macaques.
Uterus transplantation (UTx) is a potential option for women with uterine factor infertility to have a child. The clinical features indicating irreversible rejection of the uterus are unknown. In our experimental series of allogeneic UTx in cynomolgus macaques, six female macaques were retrospectively examined, which were unresponsive to treatment with immunosuppressants (i.e. irreversible rejection). Clinical features including general condition, hematology, uterine size, indocyanine green (ICG) fluorescence imaging by laparotomy, and histopathological findings of the removed uterus were evaluated. In all cases, general condition was good at the time of diagnosis of irreversible rejection and thereafter. Laboratory evaluation showed temporary increases in white blood cells, lactate dehydrogenase and C-reactive protein, then these levels tended to decrease gradually. In transabdominal ultrasonography, the uterus showed time-dependent shrinkage after transient swelling at the time of diagnosis of irreversible rejection. In laparotomy, a whitish transplanted uterus was observed and enhancement of the transplanted uterus was absent in ICG fluorescence imaging. Histopathological findings in each removed uterus showed hyalinized fibrosis, endometrial deficit, lymphocytic infiltration and vasculitis. These findings suggest that uterine transplantation rejection is not fatal, in contrast to rejection of life-supporting organs. Since the transplanted uterus with irreversible rejection atrophies naturally, hysterectomy may be unnecessary.


Artemisinins.
Artemisinins were discovered to be highly effective antimalarial drugs shortly after the isolation of the parent artemisinin in 1971 in China. These compounds combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinin containing regimens meet the urgent need to find effective treatments for multidrug resistant malaria and have recently been advocated for widespread deployment. Comparative trials of artesunate and quinine for severe malaria are in progress to see if the persistently high mortality of this condition can be reduced.


Gold Nanocomposite Contact Lenses for Color Blindness Management.
Color vision deficiency (CVD) is an ocular congenital disorder that affects 8% of males and 0.5% of females. The most prevalent form of color vision deficiency (color blindness) affects protans and deutans and is more commonly known as "red-green color blindness". Since there is no cure for this disorder, CVD patients opt for wearables that aid in enhancing their color perception. The most common wearable used by CVD patients is a form of tinted glass/lens. Those glasses filter out the problematic wavelengths (540-580 nm) for the red-green CVD patients using organic dyes. However, few studies have addressed the fabrication of contact lenses for color vision deficiency, and several problems related to their effectiveness and toxicity were reported. In this study, gold nanoparticles are integrated into contact lens material, thus forming nanocomposite contact lenses targeted for red-green CVD application. Three distinct sets of nanoparticles were characterized and incorporated with the hydrogel material of the lenses (pHEMA), and their resulting optical and material properties were assessed. The transmission spectra of the developed nanocomposite lenses were analogous to those of the commercial CVD wearables, and their water retention and wettability capabilities were superior to those in some of the commercially available contact lenses used for cosmetic/vision correction purposes. Hence, this work demonstrates the potential of gold nanocomposite lenses in CVD management and, more generally, color filtering applications.


Ursa: A Comprehensive Multi-Omics Toolbox for High-Throughput Single-Cell Analysis.
The burgeoning amount of single-cell data has been accompanied by revolutionary changes to computational methods to map, quantify and analyze the outputs of these cutting-edge technologies. Many are still unable to reap the benefits of these advancements due to the lack of bioinformatics expertise. To address this issue, we present Ursa, an automated single-cell multi-omics R package containing six automated single-cell omics and spatial transcriptomics workflows. Ursa allows scientists to carry out post-quantification single or multi-omics analyses in genomics, transcriptomics, epigenetics, proteomics, and immunomics at the single-cell level. It serves as a one-stop analytic solution by providing users with outcomes to quality control assessments, multi-dimensional analyses such as dimension reduction and clustering, and extended analyses such as pseudo-time trajectory and gene-set enrichment analyses. Ursa aims bridge the gap between those with bioinformatics expertise and those without by providing an easy-to-use bioinformatics package for scientists in hoping to accelerate their research potential. Ursa is freely available at https://github.com/singlecellomics/ursa.


The role of an active site histidine in the catalytic mechanism of aspartate transcarbamoylase.
Although the allosteric enzyme aspartate transcarbamoylase from Escherichia coli has been the focus of numerous physical and enzymological studies for over 2 decades, the catalytic mechanism is still poorly understood. There has been much speculation regarding the role of a conserved histidine residue at position 134 which recent crystallographic studies have implicated in the catalytic mechanism as a general acid or as a general base. We have used a combination of site-directed mutagenesis, 13C-isotope incorporation, and high field NMR to probe the role of His134 in the catalytic mechanism of aspartate transcarbamoylase. By comparing the wild-type catalytic trimer with that from a partially active mutant in which His134 is replaced by alanine, we have assigned the 13C resonance for His134 in the wild-type enzyme. This residue is shown to have a pK less than 6, indicating that the imidazole ring is unprotonated at pH values optimal for enzymatic activity (pH 8.0). This result eliminates the possibility of His134 participating as a general acid in the carbamoyl transfer mechanism. Since the crystallographic studies indicate that His134 is close enough to hydrogen-bond to the carbonyl of the liganded bisubstrate analog N-(phosphonacetyl)-L-aspartate, the imidazole ring would be oriented as to make it unlikely that the N1 lone pair of electrons could participate in general base catalysis. Moreover, if His134 is implicated in base catalysis, we would have expected a much greater loss of activity upon its replacement by alanine. Perhaps the role of His134 is merely to help position the carbonyl group of carbamoyl phosphate for nucleophilic attack by the alpha-amino group of aspartate.


Community-Augmented Meta-Analyses: Toward Cumulative Data Assessment.
We present the concept of a community-augmented meta-analysis (CAMA), a simple yet novel tool that significantly facilitates the accumulation and evaluation of previous studies within a specific scientific field. A CAMA is a combination of a meta-analysis and an open repository. Like a meta-analysis, it is centered around a psychologically relevant topic and includes methodological details and standardized effect sizes. As in a repository, data do not remain undisclosed and static after publication but can be used and extended by the research community, as anyone can download all information and can add new data via simple forms. Based on our experiences with building three CAMAs, we illustrate the concept and explain how CAMAs can facilitate improving our research practices via the integration of past research, the accumulation of knowledge, and the documentation of file-drawer studies.


Modeling and analysis of equipment managers in manufacturing execution systems for semiconductor packaging.
Equipment Managers (EMs) play a major role in a Manufacturing Execution System (MES). They serve as the communication bridge between the components of an MES and the equipment. The purpose of this paper is to propose a novel methodology for developing analytical and simulation models for the EM such that the validity and performance of the EM can be evaluated. Domain knowledge and requirements are collected from a real semiconductor packaging factory. By using IDEFO and state diagrams, a static functional model and a dynamic state model of the EM are built. Next, these two models are translated into a Petri net model. This allows qualitative and quantitative analyses of the system. The EM net model is then expanded into the MES net model. Therefore, the performance of an EM in the MES environment can be evaluated. These evaluation results are good references for design and decision making.


Demonstration of a hitless bypass switch using nanomechanical perturbation for high-bitrate transparent networks.
We demonstrate an optical hitless bypass switch based on nanomechanical proximity perturbation for high-bitrate transparent networks. Embedded in a single-level pi-imbalanced Mach-Zehnder interferometer, the two nanomechanical-based Deltabeta-directional couplers permit broadband signal rerouting on-chip, while the selected wavelength remains unaffected at all times for optical filter reconfiguration. The optical hitless switch is implemented in the silicon nanophotonics platform, with experimental measurements matching well with numerical and theoretical modeling.


Carbon emissions and low-carbon development in Olefin industry.
Olefin industry as a vital part in economic development is facing a problem of high CO2 emission. In this work, for the global and China's olefin industry under different development scenario, the carbon emission is predicted after the revealing of carbon footprint in different olefin routes. The results show that the carbon footprint of the natural gas liquids (NGLs)-derived route is highly lower than that of the oil- and coal-derived routes. The carbon emission from the global olefin industry in 2015 is 553 million ton CO2 (MtCO2). In 2030, it will be ranged between 739 and 924 MtCO2 under different scenarios. Under sustainable development scenario, 15% reduction space is existed, whereas 6% growth is observed under the hybrid-development scenario compared to the business-as-usual situation. In the case of China, its carbon emission is 120 MtCO2 in 2015. Its potential carbon emission in 2030 will increase to 264-925 MtCO2, depending on the rest new capacity from low-carbon or high-carbon routes. The large gap implies the significant influence of the development route choice. However, if most new capacity is from the existed planned olefin projects, the carbon emission will be ranged between 390 and 594 MtCO2. Finally, the low-carbon roadmaps as well as polices are proposed for sustainable development of olefin industry.


Trabecular organization of the proximal femur in Paranthropus robustus: Implications for the assessment of its hip joint loading conditions.
Reconstruction of the locomotor repertoire of the australopiths (Australopithecus and Paranthropus) has progressively integrated information from the mechanosensitive internal structure of the appendicular skeleton. Recent investigations showed that the arrangement of the trabecular network at the femoral head center is biomechanically compatible with the pattern of cortical bone distribution across the neck, both suggesting a full commitment to bipedalism in australopiths, but associated with a slightly altered gait kinematics compared to Homo involving more lateral deviation of the body center of mass over the stance limb. To provide a global picture in Paranthropus robustus of the trabecular architecture of the proximal femur across the head, neck and greater trochanter compartments, we applied techniques of virtual imaging to the variably preserved Early Pleistocene specimens SK 82, SK 97, SK 3121, SKW 19 and SWT1/LB-2 from the cave site of Swartkrans, South Africa. We also assessed the coherence between the structural signals from the center of the head and those from the trabecular network of the inferolateral portion of the head and the inferior margin of the neck, sampling the so-called vertical bundle, which in humans represents the principal compressive system of the joint. Our analyses show a functionally related trabecular organization in Pa. robustus that closely resembles the extant human condition, but which also includes some specificities in local textural arrangement. The network of the inferolateral portion of the head shows a humanlike degree of anisotropy and a bone volume fraction intermediate between the extant human and the African ape patterns. These results suggest slight differences in gait kinematics between Pa. robustus and extant humans. The neck portion of the vertical bundle revealed a less biomechanically sensitive signal. Future investigations on the australopith hip joint loading environment should more carefully investigate the trabecular structure of the trochanteric region and possible structural covariation between cortical bone distribution across the neck and site-specific trabecular properties of the arcuate bundle.


Exosomal lncRNAs and cancer: connecting the missing links.
Extracellular vesicles (EVs), including exosomes and microvesicles, are potent and clinically valuable tools for early diagnosis, prognosis and potentially the targeted treatment of cancer. The content of EVs is closely related to the type and status of the EV-secreting cell. Circulating exosomes are a source of stable RNAs including mRNAs, microRNAs and long non-coding RNAs (lncRNAs). This review outlines the links between EVs, lncRNAs and cancer. We highlight communication networks involving the tumor microenvironment, the immune system and metastasis. We show examples supporting the value of exosomal lncRNAs as cancer biomarkers and therapeutic targets. We demonstrate how a system biology approach can be used to model cell-cell communication via exosomal lncRNAs and to simulate effects of therapeutic interventions. In addition, we introduce algorithms and bioinformatics resources for the discovery of tumor-specific lncRNAs and tools that are applied to determine exosome content and lncRNA function. Finally, this review provides a comprehensive collection and guide to databases for exosomal lncRNAs. Supplementary data are available at Bioinformatics online.


Relevant issues in the monitoring and the toxicology of antidepressants.
This review provides specific information concerning the interpretation and usefulness of antidepressant drug monitoring. Fifteen antidepressants (ADs) were selected based on their importance in the 7 major markets (Japan, USA, France, United Kingdom, Italy, Spain, Germany) according to the Cognos Plus Study #11. Literature data were reviewed concerning monitoring of the tricyclic ADs amitriptyline, clomipramine, imipramine, and new generation antidepressants such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, mianserin, mirtazapine, bupropion, and milnacipran. In addition, St.-John's Wort was added as this natural antidepressant is very popular in Europe. The objectives of therapeutic drug monitoring (TDM) for old and new generation ADs differs, as older ADs have narrow therapeutic windows with higher risks of severe drug interactions, while the new ADs have a wide therapeutic range, but an unclear plasma concentration-effect relationship. Therefore, the purpose of TDM for new-generation ADs leads more to the monitoring of patient compliance and special patient groups such as the elderly, patients with liver and kidney impairment, patients with poor metabolism by CYP 450 and comedication with inhibitors and inducers of those enzymes.


Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease?
Assessments were made of 945 consecutive hospital patients with regard to a relation between borderline low thyroid function (recognised by a slightly raised thyroid stimulating hormone), thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid stimulating hormone of 4.0 mU/l or over had a higher prevalence of coronary heart disease than did age-matched controls, and this difference was significant in women. The excess of coronary heart disease was not explained by an excess of other risk factors such as a high cholesterol, hypertension, smoking, and diabetes. Women with thyroid antibodies had a slightly higher prevalence of coronary heart disease despite the unexpected finding of a lower serum cholesterol. The data point to an association between borderline thyroid function and autoimmunity and coronary heart disease which is not mediated through a raised serum cholesterol.


Study protocol: evaluation of 'JenMe', a commercially-delivered weight management program for adolescents: a randomised controlled trial.
Early lifestyle intervention with overweight and obese adolescents could help to avoid serious health events in early adulthood, ultimately alleviating some of the strain on the public health system due to obesity-related morbidity. Commercial weight loss programs have wide reach into the community setting, and have demonstrated success in long term weight management in adults, beyond that of current public health care. Commercial weight-management programs have not been evaluated as a method of delivery for overweight and obese adolescents. This study aims to evaluate the efficacy of a new adolescent weight management program in a commercial environment. One hundred and forty adolescents, 13 to 17 years old, will be randomised to either a weight management program intervention or a wait-listed group for 12 weeks. The commercial program will consist of a combined dietary and lifestyle approach targeting improved health behaviours for weight-loss or weight-stability. Participants will be overweight or obese (above the 85(th) percentile for BMI) and without existing co-morbidities. Outcome measures will be assessed at baseline and after 12 weeks. Primary outcome measures will be changes in BMI Z-score and waist-height ratio. Secondary outcome measures will include changes in behaviour, physical activity and psychosocial wellbeing. Intervention participants will be followed up at 6 months following completion of the initial program. Ethics approval has been granted from the Monash University Human Research Ethics Committee (CF11/3687-2011001940). This independent evaluation of a weight management program for adolescents, delivered in a commercial setting, will provide initial evidence for the effectiveness of such programs; which may offer adolescents an avenue of weight-management with ongoing support prior to the development of obesity related co-morbidities. The protocol for this study is registered with the International Clinical Trials Registry ISRCTN13602313.


Uptake of latex particles by pulmonary macrophages: role of calcium.
The uptake of latex particles by both viable and fixed hamster pulmonary macrophages was calcium and trypsin sensitive. Particle uptake did not stimulate the uptake of 45Ca. However, when 45Ca uptake was stimulated with A23187, particle uptake was inhibited. When cobalt was added with A23187, the uptake of 45Ca was inhibited and particle uptake returned to control levels. A23187, cytochalasin B, and A23187 plus cytochalasin B all reduced particle uptake to the same extent. Although both A23187 and ouabain produced similar changes in the intracellular levels of Na+ and K+, only A23187 inhibited particle uptake. We conclude that extracellular Ca2+ promotes particle-cell binding through its interaction with a trypsin-sensitive receptor in the pulmonary macrophage membrane. In contrast, elevated intracellular Ca2+ levels inhibit particle ingestion but not attachment.


Heterophilic binding of the adhesion molecules poliovirus receptor and immunoglobulin superfamily 4A in the interaction between mouse spermatogenic and Sertoli cells.
The cell adhesion protein immunoglobulin superfamily 4A (IGSF4A) is expressed on the surfaces of spermatogenic cells in the mouse testis. During spermatogenesis, IGSF4A is considered to bind to the surface of Sertoli cells in a heterophilic manner. To identify this unknown partner of IGSF4A, we generated rat monoclonal antibodies against the membrane proteins of mouse Sertoli cells grown in primary culture. Using these monoclonal antibodies, we isolated a clone that immunostained Sertoli cells and reacted with the product of immunoprecipitation of the homogenate of mouse testis with anti-IGSF4A antibody. Subsequently, to identify the Sertoli cell membrane protein that is recognized by this monoclonal antibody, we performed expression cloning of a cDNA library from the mouse testis. As a result, we identified poliovirus receptor (PVR), which is another IGSF-type cell adhesion molecule, as the binding partner of IGSF4A. The antibodies raised against PVR and IGSF4A immunoprecipitated both antigens in the homogenate of mouse testis. Immunoreactivity for PVR was present in Sertoli cells but not in spermatogenic cells at all stages of spermatogenesis. Overexpression of PVR in TM4, a mouse Sertoli cell line, increased more than three-fold its capacity to adhere to Tera-2, which is a human cell line that expresses IGSF4A. These findings suggest that the heterophilic binding of PVR to IGSF4A is responsible, at least in part, for the interaction between Sertoli and spermatogenic cells during mouse spermatogenesis.


Risk Factors of Sexual Dysfunction in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study.
Hidradenitis suppurativa (HS) has a high impact on quality of life. However, sexual health has scarcely been investigated. To describe the frequency of sexual dysfunction (SD) in women and erectile dysfunction (ED) in men with HS and to explore potential risk factors. We conducted a cross-sectional study using a crowd-sourced online questionnaire spread by the Spanish hidradenitis suppurativa patients' association (ASENDHI). In total, 393 participants answered the questionnaire. SD was found in 51% (95% CI 45-57%) of women and ED in 60% (95% CI 49-70%) of men. Factors related to SD were education status, patient's global assessment for disease activity, numeric rating scale for pain and unpleasant odour and the absence of a stable relationship. Factors related to ED were increasing age, the presence of active lesions in the genital area and the number of areas affected by active lesions. There is a high prevalence of SD and ED in HS patients. Being in a stable relationship has been a protective factor of SD in women. The results suggest that sexual impairment in HS patients is due, at least in part, to disease activity, symptoms and active lesions.


Polychromatic emission in a wide energy range from InP-InAs-InP multi-shell nanowires.
InP-InAs-InP multi-shell nanowires (NWs) were grown in the wurtzite (WZ) or zincblende (ZB) crystal phase and their photoluminescence (PL) properties were investigated at low temperature (≈6 K) for different measurement geometries. PL emissions from the NWs were carefully studied in a wide energy range from 0.7 to 1.6 eV. The different features observed in the PL spectra for increasing energies are attributed to four distinct emitting domains of these nano-heterostructures: the InAs island (axially grown), the thin InAs capping shell (radially grown), the crystal-phase quantum disks arising from the coexistence of InP ZB and WZ segments in the same NW, and the InP portions of the NW. These results provide a useful frame for the rational implementation of InP-InAs-InP multi-shell NWs containing various quantum confined domains as polychromatic optically active components in nanodevices for quantum information and communication technologies.


Alcohol consumption and the risk of endometrial cancer: a meta-analysis.
Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with alcohol consumption. Therefore, we conduct a meta-analysis of studies that assessed the association of alcohol consumption and the risk of endometrial cancer. A systematic literature search up to April 2010 was performed in MEDLINE and EMBASE, and study-specific risk estimates were pooled using a random-effects model. In the present study, six prospective and 14 case-control studies were included. Alcohol intake was not significantly associated with the risk of endometrial cancer among prospective studies (relative risk (RR): 1.04; 95% confidence interval (CI): 0.91-1.18) or among case-control studies (odds ratio (OR): 0.89; 95% CI: 0.76-1.05). However evidence from the results of our stratified analyses revealed that increased risk of endometrial cancer was associated with liquor consumption (RR: 1.22; 95% CI: 1.03-1.45) but null association with wine and beer consumption. In conclusion, alcohol consumption is not associated with the risk of endometrial cancer. Future studies should also examine whether the relation varies according to different type of alcoholic beverages.


Synopsis of recent guidelines on pancreatic exocrine insufficiency.
In recent years, three national gastroenterology societies established guidelines for the diagnosis and therapy of pancreatic exocrine insufficiency (PEI). In addition, the Cochrane Collaboration issued a review. The purpose of this paper is to present an overview of the recommendations and concordance between the four recent published guidelines and stimulate further discussion. A review of the Australian, German and Italian guidelines and the Cochrane review was conducted, and a synthesis was made of common statements. There is a high degree of agreement on almost all items within these guidelines, both in the diagnosis of PEI and in terms of therapy and approach to management of PEI. In addition, novel emerging developments are highlighted, such as the fecal elastase-1 test, which is widely used but is not suitable for measuring mild-to-moderate PEI despite its ability to positively establish the diagnosis of severe PEI. One of the few novel tests proving to be useful is the (13)C mixed-chain triglycerides (MCT) breath test. This test, albeit an excellent quantitative test, is not widely used and is rarely available. The use of this test is making it apparent that there is a difference between treating the symptoms of PEI and treating malnutrition, the broader underlying defect. This may have direct consequences for the dosing of pancreatic enzymes (pancreatin), in that the consensus starting dose of all guidelines may be too low for some patients. Although chronic pancreatitis in adults and cystic fibrosis in children account for the main evidence base used for PEI, other indications are also discussed. There is good concordance between recommendations provided by international groups. More prospective studies are required in many areas, including the use of pancreatic enzymes in other gastrointestinal disorders, such as celiac disease and irritable bowel syndrome (IBS). We also need to assess the feasibility of the (13)C MCT breath test. At the same time, it needs to be confirmed that higher doses of pancreatic enzymes are really necessary to not only relieve the symptoms of PEI but also treat malnutrition appropriately.


GSH2 promoter methylation in pancreatic cancer analyzed by quantitative methylation-specific polymerase chain reaction.
Tumor suppressor gene silencing via promoter hypermethylation is an important event in pancreatic cancer pathogenesis. Aberrant DNA hypermethylation events are highly tumor specific, and may provide a diagnostic tool for pancreatic cancer patients. The objective of the current study was to identify novel methylation-related genes that may potentially be used to establish novel therapeutic and diagnostic strategies against pancreatic cancer. The methylation status of the GS homeobox 2 (GSH2) gene was analyzed using the sodium bisulfite sequencing method. The GSH2 methylation ratio was examined in primary carcinomas and corresponding normal tissues derived from 47 patients with pancreatic cancer, using quantitative methylation-specific polymerase chain reaction. Methylation ratios were found to be associated with the patient's clinicopathological features. GSH2 gene methylation was detected in 26 (55.3%) of the 47 pancreatic cancer patients, indicating that it occurs frequently in pancreatic cancer. A significant association with methylation was observed for tumor-node-metastasis stage (P=0.031). GSH2 may be a novel methylation-sensitive tumor suppressor gene in pancreatic cancer and may be a tumor-specific biomarker of the disease.


Mitochondrial function modulates touch signalling in Arabidopsis thaliana.
Plants respond to short- and long-term mechanical stimuli, via altered transcript abundance and growth respectively. Jasmonate, gibberellic acid and calcium have been implicated in mediating responses to mechanical stimuli. Previously it has been shown that the transcript abundance for the outer mitochondrial membrane protein of 66 kDa (OM66), is induced several fold after 30 min in response to touch. Therefore, the effect of mitochondrial function on the response to mechanical stimulation by touch at 30 min was investigated. Twenty-five mutants targeting mitochondrial function or regulators revealed that all affected the touch transcriptome. Double and triple mutants revealed synergistic or antagonistic effects following the observed responses in the single mutants. Changes in the touch-responsive transcriptome were localised, recurring with repeated rounds of stimulus. The gene expression kinetics after repeated touch were complex, displaying five distinct patterns. These transcriptomic responses were altered by some regulators of mitochondrial retrograde signalling, such as cyclic dependent protein kinase E1, a kinase protein in the mediator complex, and KIN10 (SnRK1 - sucrose non-fermenting related protein kinase 1), revealing an overlap between the touch response and mitochondrial stress signalling and alternative mitochondrial metabolic pathways. Regulatory network analyses revealed touch-induced stress responses and suppressed growth and biosynthetic processes. Interaction with the phytohormone signalling pathways indicated that ethylene and gibberellic acid had the greatest effect. Hormone measurements revealed that mutations of genes that encoded mitochondrial proteins altered hormone concentrations. Mitochondrial function modulates touch-induced changes in gene expression directly through altered regulatory networks, and indirectly via altering hormonal levels.


Dynamics of metabolism and its interactions with gene expression during sporulation in Saccharomyces cerevisiae.
The dynamics of metabolism has been shown to be involved in the triggering of events that are concurrent with sporulation of the budding yeast Saccharomyces cerevisiae. Indeed, quantitative correlations have been demonstrated between sporulation and the rate of carbon substrate or oxygen consumption, and the fluxes through gluconeogenic and glyoxylate cycle pathways. The results suggest that an imbalance between catabolic and anabolic fluxes influences the occurrence of the differentiation process. The hypothesis that the initiation of sporulation is triggered by the accumulation of an intracellular metabolite is confronted with the notion that intermediary metabolism and the expression of genes involved in sporulation interact to trigger the differentiation process. Several pieces of evidence indicate that derepression of the gluconeogenic pathway is crucial for the initiation of sporulation. One of the possible pathways through which glucose repression hampers sporulation might be the repression of gluconeogenesis as well as that of respiratory activity, in turn modulating the expression of IMEL++. The stages defined in the dynamics of sporulating cultures, namely readiness and commitment, are related to metabolic events associated with sporulation. An interpretation in terms of metabolic flux dynamics is given to the reversal of commitment occurring when the normal progression to sporulation is somehow blocked. The quantitative data are here integrated in a model attempting to simulate the dynamics of metabolic as well as cellular events during sporulation. The model is envisaged as a test of the hypothesis that an imbalance between anabolism and catabolism is involved in initiation of the sporulation process. It is proposed that such an imbalance may be a signal for differential gene expression associated with the differentiation pathway.


Asymptomatic Meckel's diverticulum in adults: is diverticulectomy indicated?
The objective of this study was to estimate the incidence of the Meckel's diverticulum (MD) and to study its clinical profile and surgical outcome, as well as to check whether diverticulectomy is indicated for asymptomatic MD in adults. This is a prospective study of 1332 patients who were operated upon for acute abdomen during the period August 1999 to July 2009 in a single surgical unit. Preoperative abdominal ultrasonography and plain x-ray abdomen (erect) were done depending on the necessity. These patients were subjected to laparotomy/ appendicectomy depending on the case. A search for MD was done, and if found, surgical resection and analysis by histopathological confirmation of the resected MD were performed. During the operation, this study detected 15 (1.13%) patients with MD. In none of these cases, preoperative diagnosis of Meckel's diverticulitis was made. The age of the patients ranged from 18 to 68 years (mean age, 32.9 years). Out of 15 patients, 9 (60%) were males; 6 (40%) were females. Seven (46.7%) cases were symptomatic due to MD and 8 (53.3%) were asymptomatic. One patient presented with hematochezia; 2, with intestinal obstruction due to gangrene of the MD; and 4, with Meckel's diverticulitis. One patient had duplication of (double) Meckel's diverticulum without any inflammation in both the diverticulae. Histopathological examination of these specimens confirmed 4 cases with inflammation; 2, with gangrene; and 1, with ulcerated gastric mucosa in the MD. Among these, in 2 (13.3%) cases there was heterotopic epithelium (ulcerated gastric mucosa- 1, colonic mucosa- 1). We recommend that a search for MD in every case of appendicectomy/ laparotomy done for acute abdomen should be conducted, and if found, Meckel's diverticulectomy or resection should be performed to avoid secondary complications arising from it.


Genotoxic and cytotoxic effects of 50 Hz 1 mT electromagnetic field on larval rainbow trout (Oncorhynchus mykiss), Baltic clam (Limecola balthica) and common ragworm (Hediste diversicolor).
The aim of this research was to assess genotoxicity and cytotoxicity responses in aquatic animals exposed to 50 Hz 1 m T electromagnetic field (EMF). Rainbow trout (Oncorhynchus mykiss) at early stages of development were exposed to EMF for 40 days, whereas marine benthic invertebrates - the common ragworm Hediste diversicolor and the Baltic clam Limecola balthica - for 12 days. To define genotoxicity and cytotoxicity responses in selected animals, assays of nuclear abnormalities in peripheral blood erythrocytes of O. mykiss, coelomocytes of H. diversicolor and gill cells of L. balthica were performed. Induction of formation of micronuclei (MN), nuclear buds (NB), nuclear buds on filament cells (NBf) and cells with blebbed nuclei (BL) were assessed as genotoxicity endpoints, and 8-shaped nuclei, fragmented (Fr), apoptotic (Ap) and binucleated (BN) cells as cytotoxicity endpoints. Exposure to EMF affected all studied species but with varying degrees. The strongest responses to EMF treatment were elicited in L. balthica, in which six out of the total eight analyzed geno- and cytotoxicity endpoints were significantly elevated. Significantly induced frequencies of MN were detected in O. mykiss and H. diversicolor cells, NBf and BL only in gill cells of L. balthica, and NB in analyzed tissues of all the test species. As cytotoxicity endpoints, a significant elevation in frequencies of cells with 8-shaped nuclei was found in O. mykiss and L. balthica, while Ap and BN was observed only in L. balthica. EMF exposure did not induce any significant cytotoxic activity in H. diversicolor coelomocytes. The present study is the first to reveal the genotoxic and cytotoxic activity of 1 m T EMF in aquatic animals, and, consequently, the first one to report the adverse effect of this factor on common marine invertebrates and early life stages of fish.


Foliar δ13C Showed No Altitudinal Trend in an Arid Region and Atmospheric Pressure Exerted a Negative Effect on Plant δ13C.
Previous studies have suggested foliar δ13C generally increases with altitude. However, some observations reported no changes or even decreased trends in foliar δ13C. We noted that all the studies in which δ13C increased with elevation were conducted in the human regions, whereas those investigations in which δ13C did not vary or decreased were conducted in areas with water stress. Thus, we proposed that the pattern of increasing δ13C with elevation is not a general one, and that δ13C may remain unchanged or decrease in plants grown in arid environments. To test the hypothesis, we sampled plants along altitude gradients on the shady and sunny slopes of Mount Tianshan characterized by arid and semiarid climates. The measurements of foliar δ13C showed no altitudinal trends for the plants grown on either of the slopes. Therefore, this study supported our hypothesis. In addition, the present study addressed the effect of atmospheric pressure on plant δ13C by accounting for the effects of temperature and precipitation on δ13C. This study found that the residual foliar δ13C increased with increasing altitude, suggesting that atmospheric pressure played a negative role in foliar δ13C.


Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation.
Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy.


Forward engineering neuronal diversity using direct reprogramming.
The nervous system is comprised of a vast diversity of distinct neural cell types. Differences between neuronal subtypes drive the assembly of neuronal circuits and underlie the subtype specificity of many neurological diseases. Yet, because neurons are irreversibly post-mitotic and not readily available from patients, it has not been feasible to study specific subtypes of human neurons in larger numbers. A powerful means to study neuronal diversity and neurological disease is to establish methods to produce desired neuronal subtypes in vitro. Traditionally this has been accomplished by treating pluripotent or neural stem cells with growth factors and morphogens that recapitulate exogenous developmental signals. These approaches often require extended periods of culture, which can limit their utility. However, more recently, it has become possible to produce neurons directly from fibroblasts using transcription factors and/or microRNAs. This technique referred to as direct reprogramming or transdifferentiation has proven to be a rapid, robust, and reproducible method to generate mature neurons of many different subtypes from multiple cell sources. Here, we highlight recent advances in generating neurons of specific subtypes using direct reprogramming and outline various scenarios in which induced neurons may be applied to studies of neuronal function and neurological disease.


[Determining factors in the success of the treatment of ureteral lithiasis by ESWL].
Shock-wave extracorporeal lithotripsy (SWEL) is admittedly the choice method for most ureteral calculi (UC). Treatment of 1.674 UC was carried out with a Lithostar (Siemens). Endourologic support manoeuvres (ESM) were used in 11.7% patients. To determine their statistical influence on treatment's result variables such as site, size, calculus density, obstruction and functionality of the renal unit, as well as presence of ureteral malformation, were analyzed. With an average of 1.3 sessions (9100 waves) success rate was 91.8% cases. Only the variables of size, obstruction and function showed statistical significance, thus identifying through a multistep logistic regression test the subgroup of calculi less likely to succeed (calculi > 1 cm2, with severe uropathy and functional annulment or delay). Complication were rare (7.5%) and minimally relevant. We conclude than SWEL is the first choice treatment for UC regardless the location. Ureteroscopy (UR) should be considered as the first option particularly in distal (iliopelvic ureter), obstructive calculi and those of difficult radiological study.