[Electron microscopy: A clinically useful, desirable or useless tool in kidney biopsy diagnostics? (author's transl)].
Electron microscopic investigation of renal biopsies is indispensable in cases of suspected Alport's syndrome, benign (familial) hematuria, nail patella syndrome as well as for the identification of viruses, virus-like endothelial tubular structures and crystalloid deposits in cryoglobulinemia. Additional valuable information is provided for all other glomerular nephropathies especially for exact classification of glomerulonephritis. Electron microscopy can by no means be a substitute for light microscopy or immunofluorescence, respectively. Provided that clinical-pathological cooperation is optimal, best results can be obtained by simultaneous application of all three methods.


Exclusion of superinfecting homologous virus by Sindbis virus-infected Aedes albopictus (mosquito) cells.
The infection of tissue-cultured Aedes albopictus (mosquito) cells by an alphavirus ultimately results in a persistently infected cell population which can be maintained in the laboratory for years. One characteristic of this culture is that it will not support the replication of superinfecting homologous virus. We have previously shown that mosquito cells persistently infected with Sindbis virus produce an antiviral agent which when applied to uninfected mosquito cells suppresses Sindbis virus replication. The exclusion of virus replication in the antiviral-agent-treated cells is similar to the phenomenon of homologous interference described in alphavirus-infected vertebrate cells. In this study we examined the expression of homologous interference in three lines of mosquito cells and compared the expression of homologous interference to the effects of the antiviral activity. The cell lines were found to differ in their ability to express homologous interference, and evidence suggests that the mosquito cells may suppress replication by homologous interference or by the action of the antiviral agent.


Chemical communication, sexual selection, and introgression in wall lizards.
Divergence in communication systems should influence the likelihood that individuals from different lineages interbreed, and consequently shape the direction and rate of hybridization. Here, we studied the role of chemical communication in hybridization, and its contribution to asymmetric and sexually selected introgression between two lineages of the common wall lizard (Podarcis muralis). Males of the two lineages differed in the chemical composition of their femoral secretions. Chemical profiles provided information regarding male secondary sexual characters, but the associations were variable and inconsistent between lineages. In experimental contact zones, chemical composition was weakly associated with male reproductive success, and did not predict the likelihood of hybridization. Consistent with these results, introgression of chemical profiles in a natural hybrid zone resembled that of neutral nuclear genetic markers overall, but one compound in particular (tocopherol methyl ether) matched closely the introgression of visual sexual characters. These results imply that associations among male chemical profiles, sexual characters, and reproductive success largely reflect transient and environmentally driven effects, and that genetic divergence in chemical composition is largely neutral. We therefore suggest that femoral secretions in wall lizards primarily provide information about residency and individual identity rather than function as sexual signals.


Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients.
Because intravenous (iv) calcitriol has greater bioavailability than oral calcitriol, it may be more efficacious in suppressing parathyroid hormone (PTH) secretion. In this study, the pharmacokinetics and efficacy of pulse oral and i.v. calcitriol were compared. Patients were randomized to receive 2 micrograms of i.v. or oral calcitriol after each dialysis. Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis. Calcitriol bioavailability was determined from the area under the curve (AUCtime interval (hours) in pg/mL per h). After the PK phase, PTH was lowered to < 200 pg/mL by titrating calcitriol to a maximum of 12 micrograms/wk over 4 wk. Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70; when these limits were reached, calcitriol was held and then restarted at a lower dose. After i.v. administration, peak serum calcitriol exceeded that achieved orally but by 1 h, calcitriol levels were similar. The AUC0-0.5 (105 +/- 12, i.v.; 9 +/- 4, oral) and AUC0.5-1 (68 +/- 6, i.v.; 30 +/- 7, oral) were higher with i.v. (P < 0.05), but cumulative AUC0-48 did not differ. Individual t1/2 values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2. The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)). The t1/2 for i.v. calcitriol was 26 +/- 5 h for PK1 and 19 +/- 3 h for PK2 (NS, PK1 versus PK2 and oral versus i.v.). When the PK1 oral and i.v. data were combined, the mean t1/2 was 32 +/- 7 h whereas the t1/2 for PK2 (oral and i.v.) was 22 +/- 3 h (P < 0.05). Baseline PTH levels were 510 +/- 90 pg/mL and 499 +/- 79 pg/mL, oral and i.v., respectively. Serum PTH level at 22 wk was not different between oral and i.v. groups, 153 +/- 38 pg/mL and 214 +/- 124 pg/mL in i.v. (NS). The percentage of PTH suppression was 66 +/- 7.4% in the oral group and 69 +/- 12% in the i.v. group (NS). A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment, concomitant with a rise in serum calcium levels. Adverse effects were similar between groups, as were the average dosages of calcitriol and phosphate binders. In conclusion, the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism. The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels. The difference in bio-availability between the different routes does not have a clinically apparent effect. The t1/2 varied widely among individuals, whereas exposure to calcitriol may decrease the t1/2.


Rapid presumptive identification of human black pigmented Bacteroides species.
A simple and reliable technique is described for the rapid presumptive identification of black pigmented Bacteroides species of human origin. This method involved a microtitration technique that detected the hydrolysis of specific chromogenic enzyme substrates and haemagglutination of sheep erythrocytes. Pure cultures of black pigmented Bacteroides strains, representing the eight human species, were successfully differentiated and identified within 4 h by the identification scheme developed with this method. This is a highly reproducible method and the scheme should be useful in laboratories lacking the sophisticated equipment often needed for the identification of black pigmented Bacteroides.


Nocturia. A rarely recognized symptom of sleep apnea and other occult sleep disorders.
Nocturia, awakening from sleep to urinate, is a common symptom in a variety of medical disorders and in the elderly. Awakening from sleep as a result of nocturia is thought to be secondary to a sensation of urinary urgency resulting from an overextended bladder. Nocturia-related awakenings cause significant sleep disruption and fatigue in elderly patients and are correlated with an increased number of falls at night. Sleep disorders such as sleep apnea are also common in the elderly and are frequently the source of awakenings from sleep. The high incidence of both nocturia and sleep disorders in the elderly and other groups of patients suggests that sleep disorders may be the source of some awakenings from sleep usually attributed by patients to nocturia. Nocturia secondary to sleep disorders would be causatively different from nocturia secondary to pressure to urinate in common medical disorders and would require different diagnostic procedures and treatment. To determine the frequency of nocturia as a symptom of primary sleep disorders. Eighty consecutive patients, 27 women and 53 men with a mean (+/-SD) age of 58.7+/-14.1 years, undergoing polysomnography (sleep study or PSG) for the evaluation of a suspected sleep disorder and who met the sole criteria of awakening from sleep at least once and urinating voluntarily. Each patient had either a standard PSG recording or a PSG with administration of nasal continuous positive airway pressure. Immediately after each episode of nocturia during the PSG, patients were questioned about the reason they believed they had awakened. The PSG record immediately before awakening from sleep was then reviewed for potential causes of awakening. Patients were also asked on final morning awakening to fill in a questionnaire regarding their awakenings during the prior night. Patient reports were compared with the PSG to determine the accuracy of subjective reports. Patients awakened from sleep and voluntarily urinated a mean (+/- of 1.5+/-0.75 times per night for a total of 121 awakenings for the group. The majority (79.3%) of these awakenings from sleep were found to be directly secondary to sleep apnea, snoring or periodic leg movements in sleep. Patients correctly identified the source of their awakening from sleep on only five(4.9%) occasions and only once was sleep apnea correctly cited by a patient as a source of awakening during the night. Most awakenings from sleep attributed by our patients to pressure to urinate were instead a result of sleep disorders, particularly sleep apnea. The fact that patients do urinate once awake likely contributed to faulty post hoc reasoning and might have limited further inquiry by patients and their physicians in clinical settings into the actual sources of awakening from sleep. Even in those patients with well-known medical reasons for noctruria, Sleep disorders were still found to be the source of almost all awakenings from sleep. Patients were extremely poor judges of the reasons they awoke from sleep. The diagnosis of a sleep disorder should be seriously considered whenever a patient reports frequent awakenings from sleep to urinate.


Chrysin alleviates imiquimod-induced psoriasis-like skin inflammation and reduces the release of CCL20 and antimicrobial peptides.
Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.


Cloning and characterization of two alpha-glucosidases from Bifidobacterium adolescentis DSM20083.
Two alpha-glucosidase encoding genes (aglA and aglB) from Bifidobacterium adolescentis DSM 20083 were isolated and characterized. Both alpha-glucosidases belong to family 13 of the glycosyl hydrolases. Recombinant AglA (EC 220.127.116.11) and AglB (EC 126.96.36.199), expressed in Escherichia coli, showed high hydrolytic activity towards isomaltose and pnp-alpha-glucoside. The K(m) for pnp-alpha-glucoside was 1.05 and 0.47 mM and the V(max) was 228 and 113 U mg(-1) for AglA and AglB, respectively. Using pnp-alpha-glucoside as substrate, the pH optimum for AglA was 6.6 and the temperature optimum was 37 degrees C. For AglB, values of pH 6.8 and 47 degrees C were found. AglA also showed high hydrolytic activity towards isomaltotriose and, to a lesser extent, towards trehalose. AglB has a high preference for maltose and less activity towards sucrose; minor activity was observed towards melizitose, low molecular weight dextrin, maltitol, and maltotriose. The recombinant alpha-glucosidases were tested for their transglucosylation activity. AglA was able to synthesize oligosaccharides from trehalose and sucrose. AglB formed oligosaccharides from sucrose, maltose, and melizitose.


Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes.
Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10-106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.


The influence of transducer operating point on distortion generation in the cochlea.
Distortion generated by the cochlea can provide a valuable indicator of its functional state. In the present study, the dependence of distortion on the operating point of the cochlear transducer and its relevance to endolymph volume disturbances has been investigated. Calculations have suggested that as the operating point moves away from zero, second harmonic distortion would increase. Cochlear microphonic waveforms were analyzed to derive the cochlear transducer operating point and to quantify harmonic distortions. Changes in operating point and distortion were measured during endolymph manipulations that included 200-Hz tone exposures at 115-dB SPL, injections of artificial endolymph into scala media at 80, 200, or 400 nl/min, and treatment with furosemide given intravenously or locally into the cochlea. Results were compared with other functional changes that included action potential thresholds at 2.8 or 8 kHz, summating potential, endocochlear potential, and the 2 f1-f2 and f2-f1 acoustic emissions. The results demonstrated that volume disturbances caused changes in the operating point that resulted in predictable changes in distortion. Understanding the factors influencing operating point is important in the interpretation of distortion measurements and may lead to tests that can detect abnormal endolymph volume states.


[Evaluation of efficacy of cyproterone acetate monotherapy in prostatic cancer].
The trial conducted in the Primorsk Regional Cancer Hospital of Vladivostok and P. A. Herzen Moscow Research Cancer Institute studied effectiveness and tolerance of cyproteron acetate (CA) monotherapy and maximal androgenic block (MAB) (CA + surgical or CA + drug castration). A total of 70 patients with localized, locally advanced and generalized prostatic cancer entered the trial. They were divided into three groups: group 1 (54.3%) patients received CA monotherapy--300 mg/day, group 2 (27.1% patients) was exposed to MAB by surgical castration and received CA in a dose 200 mg/day, group 3 (18.6% patients) were exposed to MAB by drug castration and received 200 mg/day CA. The results obtained show that CA monotherapy and MAB have similar effectiveness in favourable prognostic signs. CA monotherapy was less toxic than CA combination with castratio.


How do clinicians become teachers? A communities of practice perspective.
There is widespread acceptance that clinical educators should be trained to teach, but faculty development for clinicians is undermined by poor attendance and inadequate learning transfer. As a result there has been growing interest in situating teacher development initiatives in clinical workplaces. The relationship between becoming a teacher and clinical workplace contexts is under theorised. In response, this qualitative research set out to explore how clinicians become teachers in relation to clinical communities and institutions. Using communities of practice (CoP) as a conceptual framework this research employed the sensitising concepts of regimes of competence and vertical (managerial) and horizontal (professional) planes of accountability to elucidate structural influences on teacher development. Fourteen hospital physicians completed developmental timelines and underwent semi-structured interviews, exploring their development as teachers. Despite having very different developmental pathways, participants' descriptions of their teacher identities and practice that were remarkably congruent. Two types of CoP occupied the horizontal plane of accountability i.e. clinical teams (Firms) and communities of junior doctors (Fraternities). Participants reproduced teacher identities and practice that were congruent with CoPs' regimes of competence in order to gain recognition and legitimacy. Participants also constructed their teacher identities in relation to institutions in the vertical plane of accountability (i.e. hospitals and medical schools). Institutions that valued teaching supported the development of teacher identities along institutionally defined lines. Where teaching was less valued, clinicians adapted their teacher identities and practices to suit institutional norms. Becoming a clinical educator entails continually negotiating one's identity and practice between two potentially conflicting planes of accountability. Clinical CoPs are largely conservative and reproductive of teaching practice whereas accountability to institutions is potentially disruptive of teacher identity and practice.


Dental Implant Osseointegration Inhibition by Nicotine through Increasing nAChR, NFATc1 Expression, Osteoclast Numbers, and Decreasing Osteoblast Numbers.
The success of dental implants is determined by the osteointegration process. Many studies state that smoking cigarettes can inhibit osseointegration, but the inhibition mechanism is still unclear.The aim of this study was to identify and analyze the effect of nicotine on the inhibition of dental implant osseointegration through the expression of nicotinic acetylcholine receptor (nAChR), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), osteoclast, and osteoblast numbers. This study is an experimental study of 16 New Zealand rabbits, randomized across two groups. Group 1 (eight rabbits) was a control group, and group 2 (eight rabbits) was a treatment group. The treatment group was given 2.5 mg/kg body weight/day of nicotine by injection 1 week before placement of the implant until the end of research. Observations were made in the first and the eighth week by measuring the number of osteoblast and osteoclast by immunohistology test and the expression of nAChR and NFATc1 by immunohistochemistry test. Data was analyzed using a one-way analysis of variance and Student's t-test. A p-value of < 0.05 was considered statistically significant. Significant differences were found between the control and treatment groups (p < 0.05). Results showed that nicotine increases the expression of nAChR and decreases the number of osteoblasts and the expression of BMP2 and osteocalcin. Nicotine inhibits the osseointegration of dental implants by increasing nAChR, NFATc1, osteoclast numbers, and decreasing osteoblast numbers.


Rapid reduction of intracellular glutathione in human bronchial epithelial cells exposed to occupational levels of toluene diisocyanate.
Toluene diisocyanate (TDI) is a recognized chemical asthmogen, yet the mechanism of this toxicity and the molecular reactions involved have not been elucidated. We have previously shown that TDI vapor forms adducts with the apical surface of the respiratory epithelium, and that it colocalizes with ciliary tubulin. In vitro, we have shown rapid reaction of TDI with glutathione (GSH) and transfer of the bisGS-TDI adduct to a sulfhydryl-containing major histocompatibility complex peptide. This study sought to determine if intracellular GSH is altered following exposure to TDI. We used the dye CellTracker Green (chloromethylfluorescein, CMFDA) for detection of glutathione. One-day and 6-day air-liquid cultures of human bronchoepithelial cells (HBE) were exposed to 20-100 ppb TDI vapor for 5, 15, or 30 min. Cells were subsequently imaged using a confocal microscope. Both 1- and 6-day cultures showed a decrease in intensity of the thiol staining as a function of the TDI exposure dose. Doses as low as 20 ppb, the current permissible exposure limit (PEL) to TDI, resulted in rapid (within 5 min) decreases in fluorescence. The decreased fluorescence was not due to cytotoxicity or decrease in either esterase or glutathione-S-transferase activity, enzymes necessary for activation of the fluorescence of CMFDA. The decrease in glutathione levels was verified using another fluorescent label, ThioGlo(TM) 1, and cell extracts. In addition, the mucus produced by 6-day air-liquid interface HBE cells in response to TDI exposure appeared to be protective, as HBE cells underlying mucus retained more fluorescence than did cells in the same cultures that were not covered with mucus. These results, along with previous data, strongly suggest that TDI enters pulmonary cells and reacts rapidly with intracellular GSH, and that this can occur at the current PEL of 20 ppb. This rapid reaction suggests the importance of cellular thiols in TDI-induced pulmonary disease.


Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression.
Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms.


[History of pain: from Greek antiquity to the 21st century].
The history of pain is one of the concepts that have divided Cartesian thinkers and mystical philosophers in the Western civilization over centuries. Depending on the historical period, different dogmas and morals intersect, oppose or attempt conciliation. The attitude towards pain evolved with the evolution of mentalities in the broad sense but also by relying on scientific discoveries in the field. Yesterday, pain was accepted or sublimated. Today, taking care of pain is a patient basic right and an obligation for the practitioner.


Regulation of actin dynamics and protein trafficking during spermatogenesis--insights into a complex process.
In the mammalian testis, extensive restructuring takes place across the seminiferous epithelium at the Sertoli-Sertoli and Sertoli-germ cell interface during the epithelial cycle of spermatogenesis, which is important to facilitate changes in the cell shape and morphology of developing germ cells. However, precise communications also take place at the cell junctions to coordinate the discrete events pertinent to spermatogenesis, namely spermatogonial renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation. It is obvious that these cellular events are intimately related to the underlying actin-based cytoskeleton which is being used by different cell junctions for their attachment. However, little is known on the biology and regulation of this cytoskeleton, in particular its possible involvement in endocytic vesicle-mediated trafficking during spermatogenesis, which in turn affects cell adhesive function and communication at the cell-cell interface. Studies in other epithelia in recent years have shed insightful information on the intimate involvement of actin dynamics and protein trafficking in regulating cell adhesion and communications. The goal of this critical review is to provide an updated assessment of the latest findings in the field on how these complex processes are being regulated during spermatogenesis. We also provide a working model based on the latest findings in the field including our laboratory to provide our thoughts on an apparent complicated subject, which also serves as the framework for investigators in the field. It is obvious that this model will be rapidly updated when more data are available in future years.


An immunohistological study of macrophages in the human fetal brain.
Brains from human fetuses of 13 to 27 weeks gestation have been examined immunohistologically for the presence of macrophages using the marker alpha-1-anti-chymotrypsin. A preliminary study demonstrated this to be a satisfactory marker of brain macrophages, although macrophages were also weakly positive for the more specific marker MAC-387. Macrophages were widely present within the cerebral hemispheres following their rapid accumulation between 14 and 16 weeks of gestation. They were identified in characteristic locations which, in the earliest gestation brains examined at 13 weeks, included the mid-line of the corpus callosum, around the optic tract and at the junction of the external and internal capsules near the apex of the putamen. Subsequently, macrophages were identified in abundance in the internal and external capsules and, by 22 weeks gestation, in the periventricular tissues. Their consistent presence and distribution indicate that at least the majority of these macrophages are a normal feature of the developing brain possibly related to remodelling processes.


'Watch out for these KILLERS!': newspaper coverage of the Sydney funnel web spider and its impact on antivenom research.
Based on a content analysis of treatments of the funnel web spider in the Sydney Morning Herald between 1955 and 1985, this paper argues that negative attitudes towards the funnel web were encouraged throughout this period in news stories, commentary, and advertisements and were demonstrated in the reported words and actions of members of the general public. Despite this opprobrium, research into a funnel web antivenom was able to proceed because of the willingness of individuals to collect the spiders and forward them to researchers. Negative attitudes towards the funnel web were able to be directed to a positive action which eventually helped to bring about the development of an antivenom, lessening the real threat posed by the spider.


Digital memory versatility of fully π-conjugated donor-acceptor hybrid polymers.
The fully π-conjugated donor-acceptor hybrid polymers Fl-TPA, Fl-TPA-TCNE, and Fl-TPA-TCNQ, which are composed of fluorene (Fl), triphenylamine (TPA), dimethylphenylamine, alkyne, alkyne-tetracyanoethylene (TCNE) adduct, and alkyne-7,7,8,8-tetracyanoquinodimethane (TCNQ) adduct, were synthesized. These polymers are completely amorphous in the solid film state and thermally stable up to 291-409 °C. Their molecular orbital levels and band gaps vary with their compositions. The TCNE and TCNQ units, despite their electron-acceptor characteristics, were found to enhance the π-conjugation lengths of Fl-TPA-TCNE and Fl-TPA-TCNQ (i.e., to produce red shifts in their absorption spectra and significant reductions in their band gaps). These changes are reflected in the electrical digital memory behavior of the polymers. Moreover, the TCNE and TCNQ units were found to diversify the digital memory modes and to widen the active polymer layer thickness window. In devices with aluminum top and bottom electrodes, the Fl-TPA polymer exhibits stable unipolar permanent memory behavior with high reliability. The Fl-TPA-TCNE and Fl-TPA-TCNQ devices exhibit stable unipolar permanent memory behavior as well as dynamic random access memory behavior with excellent reliability. These polymer devices were found to operate by either hole injection or hole injection along with electron injection, depending on the polymer composition. Overall, this study demonstrated that the incorporation of π-conjugated cyano moieties, which control both the π-conjugation length and electron-accepting power, is a sound approach for the design and synthesis of high-performance digital memory polymers. The TCNE and TCNQ polymers synthesized in this study are highly suitable active materials for the low-cost mass production of high-performance, polarity-free, programmable, volatile, and permanent memory devices that can be operated with very low power consumption, high ON/OFF current ratios, and high reliability.


The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.
The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry.


The Odyssey of Deaf Epistemology: A Search for Meaning-Making.
Deaf epistemology made a crucial contribution to an understanding of a Deaf worldview, yet did not quite encompass the "D/deaf experience." It started the conversation but seemingly stalled. In an expansion on earlier studies of Deaf epistemology, the researchers considered the question "What does it mean to be D/deaf?" D/deaf participants submitted narratives that were analyzed for common themes via grounded theory research methodology. Six open codes were identified: school, cultural capital, deficit/The Struggle, difference/empowerment, accessibility/technology, hearing technology. These themes were captured by two axial codes: journey and sense of belonging. The core category was determined to be situated homecoming, reflecting the apex of a long, frustrating journey. In a transition from a largely etic to an emic exploration of Deaf epistemology, new insights were developed about what it means to be D/deaf, as well as a new way of theorizing about Deaf epistemology.


Activity profiling of barley vacuolar processing enzymes provides new insights into the plant and cyst nematode interaction.
Vacuolar processing enzymes (VPEs) play an important role during regular growth and development and defence responses. Despite substantial attempts to understand the molecular basis of plant-cyst nematode interaction, the mechanism of VPEs functioning during this interaction remains unknown. The second-stage Heterodera filipjevi juvenile penetrates host roots and induces the formation of a permanent feeding site called a syncytium. To investigate whether infection with H. filipjevi alters plant host VPEs, the studies were performed in Hordeum vulgare roots and leaves on the day of inoculation and at 7, 14 and 21 days post-inoculation (dpi). Implementing molecular, biochemical and microscopic methods we identified reasons for modulation of barley VPE activity during interaction with H. filipjevi. Heterodera filipjevi parasitism caused a general decrease of VPE activity in infected roots, but live imaging of VPEs showed that their activity is up-regulated in syncytia at 7 and 14 dpi and down-regulated at 21 dpi. These findings were accompanied by tissue-specific VPE gene expression patterns. Expression of the barley cystatin HvCPI-4 gene was stimulated in leaves but diminished in roots upon infestation. External application of cyclotides that can be produced naturally by VPEs elicits in pre-parasitic juveniles vesiculation of their body, enhanced formation of granules, induction of exploratory behaviour (stylet thrusts and head movements), production of reactive oxygen species (ROS) and final death by methuosis. Taken together, down-regulation of VPE activity through nematode effectors promotes the nematode invasion rates and leads to avoidance of the induction of the plant proteolytic response and death of the invading juveniles.


Nutrient-responsive regulation determines biodiversity in a colicin-mediated bacterial community.
Antagonistic interactions mediated by antibiotics are strong drivers of bacterial community dynamics which shape biodiversity. Colicin production by Escherichia coli is such an interaction that governs intraspecific competition and is involved in promoting biodiversity. It is unknown how environmental cues affect regulation of the colicin operon and thus influence antibiotic-mediated community dynamics. Here, we investigate the community dynamics of colicin-producing, -sensitive, and -resistant/non-producer E. coli strains that colonize a microfabricated spatially-structured habitat. Nutrients are found to strongly influence community dynamics: when growing on amino acids and peptides, colicin-mediated competition is intense and the three strains do not coexist unless spatially separated at large scales (millimeters). Surprisingly, when growing on sugars, colicin-mediated competition is minimal and the three strains coexist at the micrometer scale. Carbon storage regulator A (CsrA) is found to play a key role in translating the type of nutrients into the observed community dynamics by controlling colicin release. We demonstrate that by mitigating lysis, CsrA shapes the community dynamics and determines whether the three strains coexist. Indeed, a mutant producer that is unable to suppress colicin release, causes the collapse of biodiversity in media that would otherwise support co-localized growth of the three strains. Our results show how the environmental regulation of an antagonistic trait shapes community dynamics. We demonstrate that nutrient-responsive regulation of colicin release by CsrA, determines whether colicin producer, resistant non-producer, and sensitive strains coexist at small spatial scales, or whether the sensitive strain is eradicated. This study highlights how molecular-level regulatory mechanisms that govern interference competition give rise to community-level biodiversity patterns.


Dispersive solid phase extraction based on cross-linked hydroxypropyl β-cyclodextrin polymers for simultaneous enantiomeric determination of three chiral triazole fungicides in water.
An efficient method is presented for simultaneous enantioselective determination of three chiral triazole fungicides (namely paclobutrazol, hexaconazole, and diniconazole) in water samples by DSPE-HPLC-UV. The perfect chiral separation of the enantiomers was achieved on a Chiralpak IH column within 15 min. In order to adsorb and enrich the analytes from water matrices, a cross-linked hydroxypropyl β-cyclodextrin polymer was synthesized. The prepared material exhibited good adsorption capacity, which was assessed by adsorption kinetic and adsorption thermodynamic experiments. One-variable-at-a-time and the response surface methodology were used to optimize the extraction parameters. Under the optimum sample preparation conditions, good linearity (2.0 ~ 800 µg L-1, R2 ≥ 0.9978), detection limits (0.6 to 1.0 µg L-1), quantitation limits (2.0 to 3.2 µg L-1), recoveries (86.7 ~ 105.8%), and the relative standard deviation (intra-day RSD ≤ 3.7%, inter-day RSD ≤ 5.1%) were obtained, satisfying the requirements of pesticides residues determination. These results demonstrated that the proposed method was applicable for routine determination of chiral triazole fungicide residues in water samples.


Novel Approaches for Preventing or Limiting Events (NAPLES III) Trial: randomised comparison of bivalirudin versus unfractionated heparin in patients at high risk of bleeding undergoing elective coronary stenting throught the femoral approach. rationale and design.
Bivalirudin (Angiox, The Medicine's Company, Parsippany, NJ), a synthetic direct thrombin inhibitor, when compared with standard antithrombotic therapy (including unfractionated heparin [UFH] alone or plus a glycoprotein IIb/IIIa inhibitor) determines a significant decrease of major and minor bleeding and similar protection against ischemic events both in elective and in urgent percutaneous coronary intervention (PCI). There is a lack of prospective clinical trial assessing the safety and the efficacy of bivalirudin compared with UFH alone in the subset of biomarker negative patients at high risk of bleeding undergoing to elective PCI through the femoral approach. This is a single-center, investigator-driven, randomized, double-blind, controlled trial ( www.clinicaltrial.gov registration: NCT01465503). Consecutive patients at high bleeding risk (score ≥10 according to Nikolsky et al.) undergoing elective PCI through the femoral approach will be screened for eligibility. Included patients will be randomized (ratio 1.1) to bivalirudin (Bivalirudin group) and UFH (UFH group). The primary endpoint will be the rate of major bleeding (REPLACE 2 criteria). We expect a major bleeding rate ≥5 % in the UFH group versus a ≤3 % event rate in the Bivalirudin group. Aiming for a 0.05 alpha and 0.80 power, a total of 662 patients will be needed. This number will be increased by about 25 % (leading to a total of ≈830 patients) because of uncertainty about expected endpoint rates. The present trial will give important information on what is the best anticoagulation regimen when performing PCI through the femoral approach in patients at high risk for bleeding.


Barriers to live and deceased kidney donation by patients with chronic neurological diseases: Implications for donor selection, donation timing, logistics, and regulatory compliance.
Live and deceased kidney donation by the numerous patients with advanced, progressive systemic neurological diseases, and other chronic neurological conditions (eg, high C-spine injury) remains largely unexplored. In a review of our current clinical practice, we identified multiple regulatory and clinical barriers. For live donation, mandatory reporting of postdonation donor deaths within 2 years constitutes a strong programmatic disincentive. We propose that the United Network for Organ Sharing should provide explicit regulatory guidance and reassurance for programs wishing to offer live donation to patients at higher risk of death during the reporting period. Under the proposal, live donor deaths within 30 days would still be regarded as donation-related, but later deaths would be related to the underlying disease. For deceased donation, donation after circulatory death (DCD) immediately following self-directed withdrawal of life-sustaining treatment ("conscious DCD") is not universally covered by existing DCD agreements with donor hospitals. Organ procurement organizations should thus systematically strive to revise these agreements. Obtaining adequate first-person consent from these communicatively severely impaired patients may be challenging. Optimized preservation and allocation protocols may maximize utilization of these DCD kidneys. Robust public debate and action by all stakeholders is necessary to lower existing barriers and maximize donation opportunities for patients with chronic neurological conditions.


Pediatric renal transplantation: Clinical analysis of 28 cases.
We performed an outcome analysis of 28 pediatric renal transplant recipients whose mean age at transplantation was 15.2 +/- 2 years (range: 11 to 17 years) and the M/F ratio, 0.75. Four patients received cadaveric grafts. One patient needed retransplantation due to primary nonfunction. Mean HLA match was 3.6 (range: 3 to 5). Immunosuppression was cyclosporine (n = 13) or tacrolimus (n = 11) or sirolimus (n = 4), as well as steroids and azathioprine or mycophenolate mofetil. Delayed graft function occurred in four patients. The main complications were arterial hypertension (n = 11), anemia (n = 4), urinary tract infection (n = 10), hypercholesterolemia (n = 7), and cytomegalovirus infection (n = 1). An acute rejection episode (ARE) occurred in four patients. ARE and hypertension rates were similar between the immunosuppressive drug groups. All the patients with graft failure were on cyclosporine (P = .03). Hemodialysis and peritoneal dialysis (median duration: 6 months) were performed preoperatively in 25 and 3 patients, respectively. The length of pretransplant dialysis was longer among patients with graft failure (P > .05). Noncompliance (10.7%) resulted in an ARE in one patient and graft loss in two patients. One patient died with a functioning graft. Primary disease recurred in one patient. The median follow-up period was 44 months (range: 6 to 157 months). Mean serum creatinine level was 1.35 +/- 0.74 mg/dL at the last follow-up. One- and 3-year graft survival rates were 92% and 86%, respectively, and patient survival was 100%, each. Seventeen patients (60.7%) continued their education after the transplantation; six started working. Successful transplantation in the pediatric age group together with intensive rehabilitation posttransplantation are important to make these children productive individuals to the society.


Low bone mineral density and risk of incident fracture in HIV-infected adults.
Prevalence rates of low bone mineral density (BMD) and bone fractures are higher among HIV-infected adults compared with the general United States (US) population, but the relationship between BMD and incident fractures in HIV-infected persons has not been well described. Dual energy X-ray absorptiometry (DXA) results of the femoral neck of the hip and clinical data were obtained prospectively during 2004-2012 from participants in two HIV cohort studies. Low BMD was defined by a T-score in the interval >-2.5 to <-1.0 (osteopenia) or ≤-2.5 (osteoporosis). We analysed the association of low BMD with risk of subsequent incident fractures, adjusted for sociodemographics, other risk factors and covariables, using multivariable proportional hazards regression. Among 1,006 participants analysed (median age 43 years [IQR 36-49], 83% male, 67% non-Hispanic white, median CD4(+) T-cell count 461 cells/mm(3) [IQR 311-658]), 36% (n=358) had osteopenia and 4% (n=37) osteoporosis; 67 had a prior fracture documented. During 4,068 person-years of observation after DXA scanning, 85 incident fractures occurred, predominantly rib/sternum (n=18), hand (n=14), foot (n=13) and wrist (n=11). In multivariable analyses, osteoporosis (adjusted hazard ratio [aHR] 4.02, 95% CI 2.02, 8.01) and current/prior tobacco use (aHR 1.59, 95% CI 1.02, 2.50) were associated with incident fracture. In this large sample of HIV-infected adults in the US, low baseline BMD was significantly associated with elevated risk of incident fracture. There is potential value of DXA screening in this population.


Mechanisms of perfect absorption in nano-composite systems.
Recently, it was noted that losses in plasmonics can also enable several useful optical functionalities. One class of structures that can maximize absorption are metal insulator metal systems. Here, we study 3-layer systems with a nano-composite metal layer as top layer. These systems can absorb almost 100% of light at visible frequencies, even though they contain only dielectrics and highly reflecting metals. We elucidate the underlying physical phenomenon that leads to this extraordinary high and broadband absorption. A comprehensive study of the particle material and shape, mirror material and dielectric spacer thickness is provided to identify their influence on the overall absorption. Thus, we can provide detailed design guidelines for realizing optical functionalities that require near-perfect absorption over specific wavelength bands. Our results reveal the strong role of lossy Fabry-Perot interference within these systems despite their thickness being well below half a wavelength.


Nonenzymatic separation of myocardial cell nuclei from whole heart tissue.
A simple and rapid nonenzymatic method has been developed to isolate myocardial cell nuclei from whole heart tissue. This method consists of a controlled disruption of cells followed by isopycnic gradient centrifugation. We have reviewed and compared our method to others more lengthy and laborious. By using a number of criteria, such as morphometric measurements, chemical composition, functional studies, specific nuclear protein markers, and mathematical analysis, we show that the nonenzymatic digestion method provides a most useful technique for the study of the biochemistry of the myocardial cell nucleus.


Item validity of the physical demands from the Dictionary of Occupational Titles for functional capacity evaluation of clients with chronic back pain.
This study assessed the item validity of 15 of the physical demands from the Dictionary of Occupational Titles (DOT), as evaluated in a new approach to functional capacity evaluation (FCE) for clients with chronic back pain, the Gibson Approach to FCE (GAPP FCE). Fifty-two occupational therapists were sent the specifications of the items in the GAPP FCE procedures and were asked to rate the items in terms of item-objective congruence, relevance and difficulty. A response rate of 59.2% was obtained. The majority of the therapists agreed that most of the items were congruent with the objectives based on the definition of the physical demands from the DOT. The items evaluating Balancing and Pushing and Pulling had the lowest item-objective congruence. The evaluation of Balancing and the Lifting, Carrying and Pushing and Pulling of loads greater than light-medium weight (10-16 kg) were not considered significantly relevant. Concerns were raised about the difficulty and safety of the evaluation of Lifting, Carrying and Pushing and Pulling with clients with chronic back pain, particularly if the therapist evaluates the manual handling of medium to heavy loads. These results may have implications for other FCEs, particularly those which are based on the DOT, or when assessing clients with chronic back pain.


Cloning and expression of the Borrelia burgdorferi lon gene.
The ATP-dependent protease Lon (La) of Escherichia coli degrades abnormal proteins and is involved in the regulation of capsular polysaccharide synthesis. In addition, mutations in the E. coli lon gene suppress temperature-sensitive mutations in other genes. The lon gene of Borrelia burgdorferi, encoding a homolog of the Lon protease, has been cloned and sequenced. The gene encodes a protein of 806 amino acids. The deduced amino acid sequence of the B. burgdorferi Lon protease shares substantial sequence identity with those of other known Lon proteases. The transcription start point of the B. burgdorferi lon gene was identified by primer extension analysis and the potential promoter did not show similarities to the consensus heat-shock promoter in E. coli. The 5'-end of the B. burgdorferi lon gene appears to suppress the temperature-sensitive phenotype of an E. coli lpxA mutant.


The regulation of the ammonia assimilatory enzymes in Rel+ and Rel- strains of Salmonella typhimurium.
The influence of the relA1 mutation on the regulation of the ammonia assimilatory enzymes, glutamate dehydrogenase (EC 188.8.131.52), glutamine synthetase (EC 220.127.116.11), and glutamate synthase (EC 126.96.36.199), was examined. When cells grown in rich media (either Luria broth or glucose-ammonia plus casamino acids) were transferred to a glucose-ammonia medium, the relA mutant failed to resume growth and did not have the same increase in any of the assimilatory enzyme activities as the rel+ strain. This effect was particularly dramatic for glutamate dehydrogenase, which increased 6-fold in the rel+ strain. Measurements of the guanosine nucleotide concentrations showed that the rel+ strain had a ppGpp concentration about 9 times that of the relA mutant 5 min after the shift to minimal medium. These results are consistent with those for other biosynthetic enzymes and show that the ammonia assimilatory enzymes require a relA product for their synthesis during shift from rich to minimal media. In addition, we examined the response of these strains to a change in nitrogen source. The relA mutant again failed to resume growth after a shift from glucose-ammonia to glucose-arginine medium. Even though the ppGpp concentration did not increase, the rel+ strain grew and increased glutamine synthetase activities about 2-fold. These changes the absence of increased ppGpp levels suggest that some other relA-mediated function is important during this change in nitrogen source.


The rapid slide agglutination test in the diagnosis of typhoid fevers and typhus.
Of 10,000 sera examined for infectious diseases by both the rapid slide agglutination and the tube agglutination tests, 128 were found positive for typhus fever and 257 for typhoid and paratyphoid infections. Of 84 of the last mentioned cases of typhoid and paratyphoid, which were confirmed by cultural examination, 45 (53.5%) were negative to the tube test, whereas only one (1.2%) was negative to the slide test. Taking the total of 385 cases in which the clinical picture was typical and either one of the two serological tests positive, the tube test was negative in 183 cases (47.2%) whereas the slide test was negative once only (0.3%). Of 201 cases in which both the slide and tube tests were positive, the slide test gave the result, on an average, six days earlier in 19 cases (10%).A control test of 139 sera from patients suffering from various other diseases gave a negative result on the slide test.


LOCAL TRANSLATION. Comment on "Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling".
Jan et al. (Research Articles, 7 November 2014, p. 716) propose that ribosomes translating secretome messenger RNAs (mRNAs) traffic from the cytosol to the endoplasmic reticulum (ER) upon emergence of the signal peptide and return to the cytosol after termination. An accounting of controls demonstrates that mRNAs initiate translation on ER-bound ribosomes and that ribosomes are retained on the ER through many cycles of translation.


Animal models of emphysema and their relevance to studies of particle-induced disease.
Emphysema is a pulmonary disease that may be exacerbated by inhaled particles. Over the years, many animal models of emphysema have been developed that may be useful in studying the effects of inhaled particles on humans with emphysema. Models have been described in many species, and many approaches have been described for inducing emphysema. Emphysema in humans is a parenchymal component of chronic obstructive pulmonary disease and frequently coexists in a complex with disease of the airways such as bronchitis. Animal models of emphysema usually recapitulate only one or a few aspects of this complex disease. Thus, the emphysema model must be selected carefully in order to answer specific questions about the interactive effects of particles and emphysema.


Low-field MRI's Spark on Implant Safety: A Closer Look at Radiofrequency Heating.
Advances in low-field magnetic resonance imaging (MRI) are making imaging more accessible without significant losses in image quality. In addition to being more cost-effective and easier to place without as much needed infrastructure, it has been publicized that the lower field strengths make MRI safer for patients with implants. To test this claim, we conducted a total of 368 simulations with wires of various lengths and geometries in a gel phantom during radiofrequency (RF) exposure at 23 MHz and 63.6 MHz (corresponding to MRI at 0.55 T and 1.5 T). Our results showed that heating in the gel around wire tips could be higher in certain cases at 0.55 T. To examine the impact on real patients, we simulated two models of patients with deep brain stimulation (DBS) implants of different lengths. These simulations provide quantitative evidence that low-field MRI is not always safer, and this paper serves to illustrate some of the basic principles involved in RF heating of elongated implants in MRI environments.Clinical Relevance- This paper illustrates the physical concepts of resonance and inductive coupling in RF heating during MRI scanning with implants through systematic simulations and discusses the impact of these principles in practice.


Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions.
Many cellular and physiological processes are coordinated by regulatory networks that produce a remarkable complexity of transcript isoforms. In the mammalian nervous system, alternative pre-mRNA splicing generates functionally distinct isoforms that play key roles in normal physiology, supporting development, plasticity, complex behaviors, and cognition. Neuronal splicing programs controlled by RNA-binding proteins, are influenced by chromatin modifications and can exhibit neuronal subtype specificity. As highlighted in recent publications, aberrant alternative splicing is a major contributor to disease phenotypes. Therefore, understanding the underlying mechanisms of alternative splicing regulation and identifying functional splicing isoforms with critical phenotypic roles are expected to provide a comprehensive resource for therapeutic development, as illuminated by recent successful interventions of spinal muscular atrophy. Here, we discuss the latest progress in the study of the emerging complexity of alternative splicing mechanisms in neurons, and how these findings inform new therapies to correct and control splicing defects.


Antioxidant properties of peel and pulp hydro extract in ten Persian pomegranate cultivars.
This study compares the antioxidant activity of ten different pomegranate cultivars grown in Iran using the ferric reducing power assay (FRAP assay), which is based on the reduction of a ferric-tripyridyl triazine complex to its ferrous, colored form in the presence of antioxidants. Aqueous solutions of known Fe(+2) concentration, in the range of 100-1000 micromol L(-1) were used for calibration. The results showed that among pulp and peel fractions the sour alac and sweet white peel cultivars had more FRAP value respectively. The pomegranate peel extract had markedly higher antioxidant capacity than the pulp extract. The peel extract of sweet white peel cultivar appeared to have more potential as a health supplement rich in natural antioxidants compared to the pulp and peel extracts of other pomegranate cultivars.


γ-Functional Iminiumthiolactones for the Single and Double Modification of Peptides.
Thiolactones (TL) can be readily incorporated into polymeric materials and have been extensively used as a ligation strategy despite their limited reactivity toward amine-containing substrates. Comparatively, iminiumthiolactones (ITL) are much more reactive, yet to this day, only the nonsubstituted ITL known as Traut's reagent is commercially available and used. In this work, we advance current TL/ITL chemistry by introducing reactive side groups to the ITL heterocycle in the γ-position, which can be orthogonally modified without affecting the ITL heterocycle itself. To study the reactivity of γ-functional ITLs, we subject one of our derivatives (γ-allyl-functional ITL 3b) to model reactions with several peptides and a chosen protein (lysozyme C). Using mild reaction conditions, we successfully demonstrate that the γ-functional ITL exhibits orthogonal and enhanced reactivity in a single or double modification while introducing a new functional handle to the biological substrate. We believe that γ-functional ITLs will advance the original Traut chemistry and open promising opportunities for the bioconjugation of biological building blocks to existing functional molecules, polymers, and materials.


Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis.
Expression of the p14ARF tumour suppressor is induced by hyperproliferative signals produced by RAS, MYC and other oncogenes. p14ARF quenches inappropriate mitogenic signaling by activating the p53 pathway, and the frequent loss of p14ARF in human cancer diminishes the duration and level of the p53 response. Consistent with this role, p14ARF accumulation can induce potent cell cycle arrest, but its role in promoting apoptosis has not been well established. Therefore we investigated the effects of p14ARF on the survival and growth of several human cell types. To avoid the toxicity associated with adenoviral-based vectors, we established inducible expression of p14ARF in p53-intact and p53-deficient human cell lines. As expected, transient and inducible expression of p14ARF induced rapid cell cycle arrest only in tumour cells expressing intact p53. Further, p14ARF expression did not promote apoptosis in primary human fibroblasts, or in any human tumour cell line tested, irrespective of p53 status. Instead, p14ARF expression sensitized cells to apoptosis in the presence of inhibitors of topoisomerase II (adriamycin) and transcription (DRB). Thus, loss of p14ARF would be an important step in the selection of apoptotic resistant tumour cells.


Post-streptococcal autoimmune disorders of the central nervous system.
Autoimmune disease has long been intertwined with investigations of infectious causes. Antibodies that are formed against an infectious agent can, through the process of molecular mimicry, also recognize healthy cells. When this occurs, the immune system erroneously destroys the healthy cells causing autoimmune disease in addition to appropriately destroying the offending infectious agent and attenuating the infectious process. The first infectious agent shown to cause a post-infectious autoimmune disorder in the central nervous system was Streptococcus pyogenes in Sydenham's chorea. The present review summarizes the most recent published findings of central nervous system diseases that have evidence of a post-streptococcal autoimmune etiology. Sydenham's chorea and other central nervous system illnesses that are hypothesized to have a post-streptococcal autoimmune etiology appear to arise from targeted dysfunction of the basal ganglia. PANDAS (pediatric autoimmune disorders associated with streptococcal infections) is the acronym applied to a subgroup of children with obsessive-compulsive disorder or tic disorders occurring in association with streptococcal infections. In addition, there are recent reports of dystonia, chorea encephalopathy, and dystonic choreoathetosis occurring as sequelae of streptococcal infection. Investigators have begun to isolate and describe antistreptococcal-antineuronal antibodies as well as possible genetic markers in patients who are susceptible to these illnesses. Clinical and research findings in both immunology and neuropsychiatry have established the existence of post-streptococcal neuropsychiatric disorders and are beginning to shed light on possible pathobiologic processes.


Mediating effects of social support on depression and quality of life among patients with HIV infection in Taiwan.
Few empirical studies have evaluated the mediating effects of quality of life (QoL) among people living with HIV/AIDS (PLWHA). The purposes of this study were to identify the predictors of QoL and to test the mediating effects of social support on depression and QoL among patients enrolled in an HIV case-management program in Taiwan. A cross-sectional, descriptive correlation design collected data from 108 HIV-infected individuals. Individuals were assessed using the Beck Depression Inventory II, the short version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF), and the Multidimensional Scale of Perceived Social Support between September 2007 and April 2010. After adjusting for sociodemographic characteristics (including age, gender, and mode of transmission) and clinical information (including CD4 count and time since diagnosis with HIV), the study findings showed that QoL was significantly and positively correlated with both social support and the initiation of highly active antiretroviral therapy (HAART), and was negatively correlated with depression and time since diagnosis with HIV. The strongest predictors for QoL were depression followed by the initiation of HAART and social support, with an R(2) of 0.40. Social support partially mediated the relationship between depression and QoL. Health professionals should enhance HIV-infected individuals' social support to alleviate the level of depression and further increase the QoL among PLWHA.


Behavioral suites mediate group-level foraging dynamics in communities of tropical stingless bees.
Competition for floral resources is a key force shaping pollinator communities, particularly among social bees. The ability of social bees to recruit nestmates for group foraging is hypothesized to be a major factor in their ability to dominate rich resources such as mass-flowering trees. We tested the role of group foraging in attaining dominance by stingless bees, eusocial tropical pollinators that exhibit high diversity in foraging strategies. We provide the first experimental evidence that meliponine group foraging strategies, large colony sizes and aggressive behavior form a suite of traits that enable colonies to improve dominance of rich resources. Using a diverse assemblage of Brazilian stingless bee species and an array of artificial "flowers" that provided a sucrose reward, we compared species' dominance and visitation under unrestricted foraging conditions and with experimental removal of group-foraging species. Dominance does not vary with individual body size, but rather with foraging group size. Species that recruit larger numbers of nestmates (Scaptotrigona aff. depilis, Trigona hyalinata, Trigona spinipes) dominated both numerically (high local abundance) and behaviorally (controlling feeders). Removal of group-foraging species increased feeding opportunities for solitary foragers (Frieseomelitta varia, Melipona quadrifasciata and Nannotrigona testaceicornis). Trigona hyalinata always dominated under unrestricted conditions. When this species was removed, T. spinipes or S. aff. depilis controlled feeders and limited visitation by solitary-foraging species. Because bee foraging patterns determine plant pollination success, understanding the forces that shape these patterns is crucial to ensuring pollination of both crops and natural areas in the face of current pollinator declines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00040-009-0055-8) contains supplementary material, which is available to authorized users.


An update on male hypogonadism therapy.
Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.


Effect of a Patient-Centered Decision Support Tool on Rates of Trial of Labor After Previous Cesarean Delivery: The PROCEED Randomized Clinical Trial.
Reducing cesarean delivery rates in the US is an important public health goal; despite evidence of the safety of vaginal birth after cesarean delivery, most women have scheduled repeat cesarean deliveries. A decision support tool could help increase trial-of-labor rates. To analyze the effect of a patient-centered decision support tool on rates of trial of labor and vaginal birth after cesarean delivery and decision quality. Multicenter, randomized, parallel-group clinical trial conducted in Boston, Chicago, and the San Francisco Bay area. A total of 1485 English- or Spanish-speaking women with 1 prior cesarean delivery and no contraindication to trial of labor were enrolled between January 2016 and January 2019; follow-up was completed in June 2019. Participants were randomized to use a tablet-based decision support tool prior to 25 weeks' gestation (n=742) or to receive usual care (without the tool) (n=743). The primary outcome was trial of labor; vaginal birth was the main secondary outcome. Other secondary outcomes focused on maternal and neonatal outcomes and decision quality. Among 1485 patients (mean age, 34.0 [SD, 4.5] years), 1470 (99.0%) completed the trial (n = 735 in both randomization groups) and were included in the analysis. Trial-of-labor rates did not differ significantly between intervention and control groups (43.3% vs 46.2%, respectively; adjusted absolute risk difference, -2.78% [95% CI, -7.80% to 2.25%]; adjusted relative risk, 0.94 [95% CI, 0.84-1.05]). There were no statistically significant differences in vaginal birth rates (31.8% in both groups; adjusted absolute risk difference, -0.04% [95% CI, -4.80% to 4.71%]; adjusted relative risk, 1.00 [95% CI, 0.86-1.16]) or in any of the other 6 clinical maternal and neonatal secondary outcomes. There also were no significant differences between the intervention and control groups in the 5 decision quality measures (eg, mean decisional conflict scores were 17.2 and 17.5, respectively; adjusted mean difference, -0.38 [95% CI, -1.81 to 1.05]; scores >25 are considered clinically important). Among women with 1 previous cesarean delivery, use of a decision support tool compared with usual care did not significantly change the rate of trial of labor. Further research may be needed to assess the efficacy of this tool in other clinical settings or when implemented at other times in pregnancy.


Feedback interactions between cell-cell adherens junctions and cytoskeletal dynamics in newt lung epithelial cells.
To test how cell-cell contacts regulate microtubule (MT) and actin cytoskeletal dynamics, we examined dynamics in cells that were contacted on all sides with neighboring cells in an epithelial cell sheet that was undergoing migration as a wound-healing response. Dynamics were recorded using time-lapse digital fluorescence microscopy of microinjected, labeled tubulin and actin. In fully contacted cells, most MT plus ends were quiescent; exhibiting only brief excursions of growth and shortening and spending 87.4% of their time in pause. This contrasts MTs in the lamella of migrating cells at the noncontacted leading edge of the sheet in which MTs exhibit dynamic instability. In the contacted rear and side edges of these migrating cells, a majority of MTs were also quiescent, indicating that cell-cell contacts may locally regulate MT dynamics. Using photoactivation of fluorescence techniques to mark MTs, we found that MTs in fully contacted cells did not undergo retrograde flow toward the cell center, such as occurs at the leading edge of motile cells. Time-lapse fluorescent speckle microscopy of fluorescently labeled actin in fully contacted cells revealed that actin did not flow rearward as occurs in the leading edge lamella of migrating cells. To determine if MTs were required for the maintenance of cell-cell contacts, cells were treated with nocodazole to inhibit MTs. After 1-2 h in either 10 microM or 100 nM nocodazole, breakage of cell-cell contacts occurred, indicating that MT growth is required for maintenance of cell-cell contacts. Analysis of fixed cells indicated that during nocodazole treatment, actin became reduced in adherens junctions, and junction proteins alpha- and beta-catenin were lost from adherens junctions as cell-cell contacts were broken. These results indicate that a MT plus end capping protein is regulated by cell-cell contact, and in turn, that MT growth regulates the maintenance of adherens junctions contacts in epithelia.


Role of the exercise pressor reflex in rats with dilated cardiomyopathy.
In heart failure, there is a sympathetically mediated hyperkinetic cardiovascular response to exercise that limits tolerance to physical activity. Alterations in skeletal muscle morphology and metabolism have led to the hypothesis that the exercise pressor reflex (EPR) becomes hyperactive after the development of cardiomyopathy and contributes to the exaggerated circulatory response elicited. To test this hypothesis, Sprague-Dawley rats were divided into the following groups: control, sham, and dilated cardiomyopathy (DCM, induced by ischemic injury). Using transthoracic echocardiography, left ventricular fractional shortening was 47+/-2%, 44+/-1%, and 24+/-2% in control, sham, and DCM rats, respectively. Activation of the EPR by electrically induced static muscle contraction resulted in significantly larger increases in mean arterial pressure and heart rate in DCM animals (32+/-2 mm Hg, 13+/-1 bpm) compared with control (20+/-1 mm Hg, 8+/-1 bpm) and sham (20+/-2 mm Hg, 8+/-1 bpm) rats. Comparable results were obtained with selective stimulation of the mechanically sensitive component of the EPR by passive muscle stretch. The augmentations in EPR and mechanoreflex activity in DCM occurred progressively over a 10-week period, becoming greater as the severity of left ventricular dysfunction increased. In DCM, the potentiated cardiovascular response to static muscle contraction is mediated, in part, by an exaggerated EPR. The muscle mechanoreflex contributes significantly to the EPR dysfunction that develops.


Changes in antibiotic susceptibility and ribotypes in Clostridium difficile isolates from southern Scotland, 1979-2004.
An increase in the incidence of clinical cases of Clostridium difficile infection has been reported in recent years, but few studies have examined changes in molecular epidemiology and antibiotic resistance over a long period of time. A collection of 179 isolates of C. difficile obtained from symptomatic adult patients in southern Scotland between 1979 and 2004 was used to determine changes in the prevalence of epidemiological types and antibiotic susceptibilities to common antibiotics. PCR ribotyping and MIC determination were performed on all isolates. A total of 56 different ribotypes were identified, among which ribotype 002 was the commonest type overall (14 .0%), followed by ribotypes 014 (7.3 %), 012 (5 .0%), 015 (5.0 %), 020 (5 .0%) and 001 (4.5 %). Ribotype 078 was also identified. The 10 commonest ribotypes comprised 55 % of the total isolates. Ribotype 001 increased in prevalence from 1.5 to 12.2 % over the study years, whereas the prevalence of ribotype 012 decreased from 8.7 to 2 .0%. Resistance to clindamycin, erythromycin and ceftriaxone was found in 95.5, 14.0 and 13.4 % of isolates, respectively. Resistance to vancomycin or metronidazole was not detected. Thirty-two (17.9 %) and 14 (7.8 %) isolates were resistant to two and three or more antibiotics, respectively. Ribotype 001 displayed maximum resistance, with 50 % of isolates resistant to erythromycin, moxifloxacin and ceftriaxone, and 100 % resistant to clindamycin. Over the 26 years of the study, antibiotic resistance and ribotype prevalence have changed, and antibiotic pressures may have been the major driver of this change.


Promotive, preventive, and treatment interventions for adolescent mental health in sub-Saharan Africa: A protocol for two scoping reviews including systematic analyses of intervention effectiveness.
The increasing prevalence of mental health difficulties amongst adolescents is a worldwide concern. Poor mental health in adolescence is associated with a range of mental, physical and social problems in later life. In sub-Saharan Africa, limited data suggests that mental disorders amongst adolescents are common. It is important that interventions to address this are rooted in an understanding of the unique local context and culture. Yet, the current use, development, and effectiveness of adolescent mental health interventions in sub-Saharan Africa is unclear. In response, this paper presents a protocol for two scoping reviews that together will examine the available evidence on promotive, preventive, and treatment interventions for adolescent mental health in sub-Saharan Africa. The scoping reviews will follow the five-step methodological framework proposed by Arksey and O'Malley, with further recommendations from the Joanna Briggs Institute. They will review scientific and grey literature published between 2000 and 2021, without restrictions in language or study type. A wide range of sources, including MEDLINE, CINAHL, Global Health, PsychINFO, Cochrane and Google Scholar will be searched. Eligibility screening and data extraction will be done by two independent reviewers, and disagreements resolved by a third reviewer. Data will be summarised in two phases. A narrative synthesis will provide a descriptive profile of all studies included and will explore key concepts related to intervention types, target populations and adaptations to local context. A systematic review element will collate evidence of intervention effectiveness from (cluster) Randomised Controlled Trials. To the best of our knowledge, these scoping reviews are the first to synthesise a wide range of available evidence on promotive, preventive and treatment interventions for adolescent mental health in sub-Saharan Africa. The results will be published in peer-reviewed publications and will be presented as an evidence base for future intervention development and implementation.


A Phase II study of high-dose paclitaxel in patients with advanced neuroendocrine tumors.
New agents with antitumor activity in patients with neuroendocrine tumors are sorely needed. A Phase II study of high-dose paclitaxel in patients with metastatic carcinoid and islet cell tumors was performed at the Mayo Clinic. Granulocyte-colony-stimulating factor (GCSF) also was administered to ameliorate neutropenia. Twenty-four patients (14 with carcinoid tumors, 9 with islet cell tumors, and 1 with an anaplastic tumor) were enrolled on this Phase II study of paclitaxel given as a 24-hour continuous infusion at a dose of 250 mg/m(2) every 3 weeks plus GCSF at a dose of 5 microg/kg/day subcutaneously, beginning 24 hours after the completion of the paclitaxel dose and continuing until the absolute neutrophil count was > 10,000/microL. All 24 patients were evaluable for analysis. The overall response rate was 8% (95% confidence interval [95% CI], 0-0.11). At last follow-up all patients except 1 had developed disease progression, with an estimated median time to disease progression of 3.2 months (95% CI, 1.6-6.0 months). The estimated median survival was 1.5 years (95% CI, 1.0-1.8 years). Hematologic toxicity was significant with 12 of 24 patients developing Grade 4 (according to the National Cancer Institute Common Toxicity Criteria scale) neutropenia; however, there were no septic deaths reported. There were 17 episodes of Grade 4 neutropenia in these 12 patients and the duration of these events ranged from 2-5 days. More common nonhematologic toxicities included arthralgia (21 patients), anorexia (15 patients), nausea (15 patients), diarrhea (12 patients), and allergic reactions (2 patients). Given the lack of antitumor activity of paclitaxel and the significant hematologic toxicity observed despite the use of GCSF support in the current study cohort of patients with neuroendocrine tumors, further studies of this combination in this particular patient population are not recommended.


Smartphone, tablet computer and e-reader use by people with vision impairment.
Consumer electronic devices such as smartphones, tablet computers, and e-book readers have become far more widely used in recent years. Many of these devices contain accessibility features such as large print and speech. Anecdotal experience suggests people with vision impairment frequently make use of these systems. Here we survey people with self-identified vision impairment to determine their use of this equipment. An internet-based survey was advertised to people with vision impairment by word of mouth, social media, and online. Respondents were asked demographic information, what devices they owned, what they used these devices for, and what accessibility features they used. One hundred and thirty-two complete responses were received. Twenty-six percent of the sample reported that they had no vision and the remainder reported they had low vision. One hundred and seven people (81%) reported using a smartphone. Those with no vision were as likely to use a smartphone or tablet as those with low vision. Speech was found useful by 59% of smartphone users. Fifty-one percent of smartphone owners used the camera and screen as a magnifier. Forty-eight percent of the sample used a tablet computer, and 17% used an e-book reader. The most frequently cited reason for not using these devices included cost and lack of interest. Smartphones, tablet computers, and e-book readers can be used by people with vision impairment. Speech is used by people with low vision as well as those with no vision. Many of our (self-selected) group used their smartphone camera and screen as a magnifier, and others used the camera flash as a spotlight.


The value of gadolinium-enhanced MRI in predicting the development of sudden hearing loss into Ménière's disease.
To compare the clinical features of sudden hearing loss (SHL) in patients with and without endolymphatic hydrops (EH), and to investigate the association between SHL with EH and Ménière's disease (MD). The clinical data of 63 SHL patients with first symptoms were evaluated retrospectively. Patients were separated into two groups based on the results of gadolinium-enhanced magnetic resonance imaging: EH and non-EH groups. Independent sample t-test and U-test were used to compare groups for continuous variables, and the chi-squared test, corrected chi-squared test and Bonferroni correction test were used to compare groups for binary and ordinal variables. The binary logistic regression model was utilised for univariate and multivariate analysis of follow-up patient prognosis. The EH and non-EH groups contained 32 and 31 patients, respectively. The EH group had a higher prevalence of low-tone descending hearing loss. Fifty-one patients were followed for more than 2 years. In the EH group, 11 and 15 patients were diagnosed with sudden sensorineural hearing loss (SSNHL) and MD, respectively, while in the non-EH group, 24 patients were diagnosed with SSNHL and only one with MD. EH, low-tone descending hearing loss and vertigo were risk factors for the diagnosis of MD in a subgroup univariate regression analysis of patients experiencing SHL. EH was found to be a risk factor for the progression of SHL into MD in a multifactor regression analysis. Patients with SHL who have EH are more likely to present with low-tone descending hearing loss. EH is a risk factor for the subsequent development of MD.


Evaluation of difference in the neurotoxicity produced by dermal application of chlorpyrifos on the neonatal and adult mice.
Dermal exposure to organophosphate pesticide is important because of its popular use. This study planned to compare the changes in serum acetylcholinesterase, paraoxonase and neuronal density of hippocampus and iso-cortex between two age groups of Swiss albino mice (18-day-old and 150-day-old) after dermal application of (1/2) LD50 of chlorpyrifos for 14 days. Statistically significant reduction was observed in serum acetylcholinesterase (Mann-Whitney test, p<0.05) and neuronal density (Independent samples t-test, p<0.05) in exposed groups compared to the control. The reduction in serum AChE and neuronal density was more pronounced in exposed adult mice than in exposed neonatal mice. The paraoxonase level was insignificant in control neonatal mice, whereas it was 890-fold more in exposed neonatal mice. Upregulated paraoxonase levels may be extrapolated to produce relatively lower reduction of cholinesterase and neuronal density in neonatal mice.


Chronic Exertional Compartment Syndrome Resolved With Running Gait Retraining: A Case Report.
A 34-year-old female athlete experienced pain, tightness, and sensation changes to her lower legs and feet when reaching approximately one mile of her run. After a wick catheter test, an orthopedic surgeon diagnosed her with chronic exertional compartment syndrome (CECS) and declared her eligible to receive a fasciotomy surgery. It is theorized that a forefoot gait can delay symptom onset of CECS and decrease the amount of discomfort the runner experiences. The patient opted to try a 6 week gait retraining program to try to alleviate symptoms nonsurgically. The purpose of this study is to provide education of the contributing factors of CECS and to determine if gait retraining is an effective alternative to invasive surgery. After six weeks of gait retraining, the patient was able to run without experiencing any CECS symptoms. She also had reduced compartment pressures leading the surgeon to no longer recommend her for a fasciotomy.


Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.
Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.


Increased brain activation during the processing of spatially invalidly cued targets.
In a spatial central cue Posner s paradigm, positions in the vertical meridian were cued in order to evaluate the neuro-cognitive consequences in the processing of validly cued (VC) and invalidly cued (IC) targets. Sixty-four EEG channels were recorded and analyzed showing that IC targets produced an enhanced P3 component with respect to VC targets. With the purpose of reinforcing the idea of increased activation during IC targets and to define the areas in which the increased activation would occur, source localization was applied to the ERPs. LORETA and single dipole localization showed that the early P3 presented a localization in the dorsal part of the anterior cingulate cortex (dACC), while the late P3 was fitted by single dipole more posterior than the early P3, and LORETA added a source in the parahippocampal gyrus in addition to the already activated dACC. LORETA results also showed a differential activation of the inferior frontal gyrus when IC targets were processed. The previous results suggest that subjects prepare to accomplish the task upon specification of the cue. Therefore, when the IC target appears, it induces the activation of the frontal cortex including areas related to the conflict monitoring system and to the processing of unexpected events. The IC targets also induce the revision of internal models about the task, possibly by activation of the temporo-mesial surface. All the obtained current source differences indicate that a higher brain activation during IC trials with respect to VC trials occurs.


Ligament of Treitz approach in laparoscopic modified radical antegrade modular pancreatosplenectomy: report of three cases.
Laparoscopic distal pancreatectomy for pancreatic cancer is being applied increasingly in selected cases. Open radical antegrade modular pancreatosplenectomy (RAMPS) was introduced to obtain a higher rate of tumor-free margins and a higher lymph node (LN) count. However, there is no standard laparoscopic technique for pancreatic cancer. We treated three patients with RAMPS using a ligament of Treitz approach. We started each procedure by dissecting the ligament of Treitz. We entered and spread the anterior space of the aorta and inferior vena cava. We then dissected the LN of the root of the supra-mesenteric artery and performed RAMPS. The mean number LN retrieved from the patients was 43 ± 22. All three patients underwent pancreatectomy to obtain tumor-free margins, and two patients began adjuvant chemotherapy by postoperative day 14. The ligament of Treitz approach in laparoscopic modified RAMPS offered tumor-free margins and the resection of sufficient regional LN. The procedure also allowed adjuvant chemotherapy to be started early.


[Factors associated with overweight in students from tri-border region: Argentina, Brazil and Paraguay].
The Tri-Border Region has several social and health problems among young people, however, there are no data about the overweight between adolescents. This study investigated the prevalence of overweight and associated factors in students from Tri-Border Region: Argentina, Brazil and Paraguay. Study participants were 1.183 students, ages from 15 to 18 years. The overweight was identified according to body mass index cut-off points proposed by the World Health Organization. The Global School-Based Student Health Survey questionnaire was used to identify sociodemographic (gender and age) and behavioral factors (physical activity outside of school, commuting to school, time watching TV and fruits, vegetables, sweet, and salty snack consumption) associated with overweight in adolescents. It was used the descriptive statistics, analysis of variance, chi-square and binary logistic regression, adopting p < 0.05. Thirteen percent of students were overweight. Boys were approximately two times more likely to have overweight than girls, independently of nationality. Brazilian students that realized passive commuting to school and Argentineans students with low consumption of vegetables (< 1 time/day) were 2.2 and 2.9 times more likely to have overweight than their counterparts who performed active commuting to school and consumed vegetables daily, respectively. These results suggest that public policies to combat overweight should attention on promoting healthy lifestyle among young people from Tri-Border Region.


Sex bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene.
Celiac disease (CeD) is an immune-mediated disorder that develops in genetically predisposed individuals upon gluten consumption. HLA risk alleles explain 40% of the genetic component of CeD, so there have been continuing efforts to uncover non-HLA loci that can explain the remaining heritability. As in most autoimmune disorders, the prevalence of CeD is significantly higher in women. Here, we investigated the possible involvement of the X chromosome on the sex bias of CeD. We performed a X chromosome-wide association study (XWAS) and a gene-based association study in women from the CeD Immunochip (7062 cases, 5446 controls). We also constructed a database of X chromosome cis-expression quantitative trait loci (eQTLs) in monocytes from unstimulated (n = 226) and lipopolysaccharide (LPS)-stimulated (n = 130) female donors and performed a Summary-data-based MR (SMR) analysis to integrate XWAS and eQTL information. We interrogated the expression of the potentially causal gene (TMEM187) in peripheral blood mononuclear cells (PBMCs) from celiac patients at onset, on a gluten-free diet, potential celiac patients and non-celiac controls. The XWAS and gene-based analyses identified 13 SNPs and 25 genes, respectively, 22 of which had not been previously associated with CeD. The X chromosome cis-eQTL analysis found 18 genes with at least one cis-eQTL in naïve female monocytes and 8 genes in LPS-stimulated female monocytes, 2 of which were common to both situations and 6 were unique to LPS stimulation. SMR identified a potentially causal association of TMEM187 expression in naïve monocytes with CeD in women, regulated by CeD-associated, eQTL-SNPs rs7350355 and rs5945386. The CeD-risk alleles were correlated with lower TMEM187 expression. These results were replicated using eQTLs from LPS-stimulated monocytes. We observed higher levels of TMEM187 expression in PBMCs from female CeD patients at onset compared to female non-celiac controls, but not in male CeD individuals. Using X chromosome genotypes and gene expression data from female monocytes, SMR has identified TMEM187 as a potentially causal candidate in CeD. Further studies are needed to understand the implication of the X chromosome in the higher prevalence of CeD in women.


Surgical options in atrial fibrillation.
Atrial fibrillation (AF) is not benign and its prevalence is increasing. The two main goals in management of atrial fibrillation are to optimize hemodynamics through rate or rhythm control and to prevent systemic thrombo-embolism. To date, these two goals are still sub-optimally achieved, raising the need for alternative methods and strategies both pharmacologically and through interventions. In this review, we discuss surgical strategies of achieving both goals with insights on the evolution and potential future of these strategies.


Impact of smoking on pathological features in oral cavity squamous cell carcinoma.
We sought to determine whether smokers with oral cavity squamous cell carcinoma (OCSCC) have tumors with more adverse pathological features than in nonsmokers and whether or not these are predictive of outcomes. We retrospectively identified 163 patients with American Joint Committee on Cancer stages I-IVa OCSCC diagnosed between 2005 and 2015 and treated with curative intent. A pathological risk score (PRS) was calculated using the National Comprehensive Cancer Network adverse risk factors: positive margin, extracapsular extension of lymph node metastases, pT3 or pT4 primary, N2 or N3 nodal disease, perineural invasion, and lymphovascular space invasion. Multivariable models were constructed to determine the independent predictors of overall survival (OS), recurrence-free survival (RFS), and PRS. A total of 108 (66.26%) were smokers and 55 nonsmokers. Three-year actuarial OS and RFS were 62% and 68% in smokers and 81% and 69% in nonsmokers, respectively (P = 0.06 and P = 0.63). Smokers were more likely to have advanced disease stage and tumors with aggressive pathological features than nonsmokers. Smokers had significantly worse PRS (mean ± standard deviation; 2.38 ± 2.19, median; 2.00) than nonsmokers (0.89 ± 1.21, 0.00) (P < 0.001). Older age, higher PRS, and smoking status were independent predictors of OS. Smoking or PRS did not predict for worse RFS. On multivariate analysis, independent predictors of PRS were smoking status and grade (P < 0.001). In patients with OCSCC, smokers have more aggressive disease as evidenced by more adverse pathological features than nonsmokers. Moreover, smoking is an independent predictor of OS but not RFS. The PRS is a significant predictor of OS and needs validation in the future studies.


Energy need in childhood and adult-onset obese women before and after a nine-month nutrition education and walking program.
The effect of a 9-month nutrition education and walking program on total calorie need, resting metabolic rate (RMR), thermic effect of food (TEF), body composition, and activity level was determined in seven women (28-41 years of age) with childhood-onset obesity (CO) and eight women (29-42 years of age) with adult-onset obesity (AO). A 3-week testing period was conducted before and after the 9-month program during which all subjects were fed a controlled, weight-maintaining metabolic diet which was used to determine daily calorie need. Body composition, RMR, and TEF were measured during the second and third weeks of both 3-week testing periods. Body weight decreased significantly for CO (mean -5.7 +/- 9.3 kg) and AO (mean -3.3 +/- 6.2 kg), but fat-free mass (FFM) was unchanged. When comparing pre to post data, mean total calorie need increased by 2.9 percent for CO and 3.1 percent for AO (P greater than 0.05), RMR decreased 3.6 percent for CO and 2.8 percent for AO (P less than 0.05), and TEF increased 11 percent for CO and 50 percent for AO (P less than 0.05). Time spent in light and moderate level activity increased significantly from pre to post. The increase in activity and TEF more than compensated for the slight decrease in RMR (mean -55 kcal/day), contributing to an overall increase in daily energy need (mean = 74 kcal/day) at the end of the program, even for the six women who lost greater than 5 kg body weight.


Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system.
CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) is a small RNA-based adaptive prokaryotic immunity system that functions by acquisition of short fragments of DNA (mainly from foreign invaders such as viruses and plasmids) and subsequent destruction of DNA with sequences matching acquired fragments. Some mutations in foreign DNA that affect the match prevent CRISPR/Cas defensive function. Here we show that matching sequences that are no longer able to elicit defense, still guide the CRISPR/Cas acquisition machinery to foreign DNA, thus making the spacer acquisition process adaptive and leading to restoration of CRISPR/Cas-mediated protection. We present evidence suggesting that after initial recognition of partially matching foreign DNA, the CRISPR/Cas acquisition machinery moves along the DNA molecule, occasionally selecting fragments to be incorporated into the CRISPR locus. Our results explain how adaptive CRISPR/Cas immunity becomes specifically directed towards foreign DNA, allowing bacteria to efficiently counter individual viral mutants that avoid CRISPR/Cas defense.