Paip1 interacts with poly(A) binding protein through two independent binding motifs.
The 3' poly(A) tail of eukaryotic mRNAs plays an important role in the regulation of translation. The poly(A) binding protein (PABP) interacts with eukaryotic initiation factor 4G (eIF4G), a component of the eIF4F complex, which binds to the 5' cap structure. The PABP-eIF4G interaction brings about the circularization of the mRNA by joining its 5' and 3' termini, thereby stimulating mRNA translation. The activity of PABP is regulated by two interacting proteins, Paip1 and Paip2. To study the mechanism of the Paip1-PABP interaction, far-Western, glutathione S-transferase pull-down, and surface plasmon resonance experiments were performed. Paip1 contains two binding sites for PABP, PAM1 and PAM2 (for PABP-interacting motifs 1 and 2). PAM2 consists of a 15-amino-acid stretch residing in the N terminus, and PAM1 encompasses a larger C-terminal acidic-amino-acid-rich region. PABP also contains two Paip1 binding sites, one located in RNA recognition motifs 1 and 2 and the other located in the C-terminal domain. Paip1 binds to PABP with a 1:1 stoichiometry and an apparent K(d) of 1.9 nM.


[Incidence of cancer in Mauritius in 1989-1993].
Systematic registration of cases of cancer was introduced in Mauritius as of 1989. This article analyzes the data concerning the incidence and mortality of the disease from 1989 to 1993. At the end of each year, the archives of the Central Laboratory of Hospitals, the admissions register at the only center for radiotherapy, the discharge résumés of patients classified as suffering from cancer of all the regional hospitals and the archives of the Medical Assistance Service regarding treatment abroad were examined and information drawn from them in order to fill out the information form of the cancer register (10 items per case). For the period studied, 4293 new cases of cancer were detected of which 1784 (41.6%) among men. The main organs affected were, for men: the lungs (12%), the mouth/pharynx (10%), and the stomach (8%); for women: the breast (24%), the cervix (21%), and the ovaries (6%). The incidence of cancer has increased at an annual average of 8% for both sexes, reaching in 1993 the standard (world) incidence of respectively 106 and 122 cases per 100,000. Over the same period, cancer rose to 2nd to 3rd place in causes of death, accounting for approximately 8 to 9% of deaths. The ratio of mortality/incidence is 0.85 among men and 0.58 among women. The distribution of cancer according to age, location and ethnic group points to interesting and significant results which can be subsequently compared to that of other countries in the region. The second phase of registering cancer in Mauritius is presently being undertaken.


A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.
Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)2 , of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat-P4 -(C5)2 disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA-receptor surface expression in vivo. Moreover, Tat-P4 -(C5)2 administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat-P4 -(C5)2 as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non-tandem protein-protein interaction domains.


The Effectiveness of Continuous Glucose Monitoring in Patients with Type 2 Diabetes: A Systematic Review of Literature and Meta-analysis.
Continuous glucose monitoring (CGM) provides glucose trend information that can be used to guide treatment and motivate patients with diabetes. Currently, the evidence on effectiveness of CGM in patients with type 2 diabetes is debatable. We aim to provide a systematic review and meta-analysis to synthesize current evidence of effectiveness of CGM in adults with type 2 diabetes. Cochrane, Embase, PubMed, and Web of Science were searched to include all studies that reported effectiveness of CGM in terms of HbA1c in adults aged 18 and older, with type 2 diabetes, on any treatment for diabetes. Heterogeneity (I2) was used to determine the variability between studies. All data were analyzed using Review Manager 5.3 software. Seven randomized controlled trials and three cohort studies, involving 1384 patients for real-time CGM (RT-CGM) and professional CGM (P-CGM) and 4902 patients for flash glucose monitoring (FGM), were included. RT-CGM and P-CGM were associated with a modest but statistically significant reduction in HbA1c of 0.20% (95% confidence interval [CI] -0.31 to -0.09) compared with control. Patients who received FGM had a nonsignificant reduction of 0.02% (95% CI -0.07 to 0.04) compared with control. The meta-analysis indicated a low heterogeneity between studies. Our analysis of current evidence suggests that RT-CGM and P-CGM are effective in improving HbA1c in adults with type 2 diabetes. Due to insufficient evidence, it is premature to form conclusions on the effectiveness of FGM. Future multicenter trials accessing the effectiveness of CGM as well as safety and cost-effectiveness may be necessary.


Atopic keratoconjunctivitis.
Atopic keratoconjunctivitis (AKC) represents a disease usually classified under the term of allergic conjunctivitis together with seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC) and vernal keratoconjunctivitis (VKC). However, AKC and VKC have clinical and pathophysiological features quite different from SAC and PAC, in spite of some common markers of allergy. This article aims to review personal studies suggesting that allergic conjunctivitis (similarly to asthma, rhinitis and atopic dermatitis) is a heterogeneous disease entity with different preferential pathogenetic mechanisms and a spectrum of clinical expression which varies according to individual cases. AKC and VKC may thus represent a model of atopy quite distinct from the classical type-1 hypersensitivity mechanism.


Protective role of normothermic, hyperthermic and estrogen preconditioning and pretreatment on tumour necrosis factor-alpha-induced damage.
Tumour necrosis factor-alpha (TNF-α) has been reported to play an important role in ischemia reperfusion injury and ischemic preconditioning (IPC). However, its role is not completely understood. Recently, normothermic IPC (NIPC), hyperthermic IPC (HIPC), preconditioning (PC) with 17-beta estradiol (estrogen, E2) and E2 pretreatment were proven to be effective in reducing ischemia reperfusion injury. To investigate the detrimental effects of TNF-α on the heart, and the protective effects of NIPC, HIPC, E2 PC and pretreatment on TNF-α-induced injury. A Langendorff-perfused rat heart model was used for the present study. Hearts isolated from male rats were studied under eight different conditions (n=5 each): negative control; control treated with TNF-α without any further treatment; NIPC (preconditioned at 37°C); HIPC (preconditioned at 42°C); E2 PC; E2 pretreatment; normal, untreated hearts plus E2; or pretreated hearts perfused for 60 min with TNF-α and an E2-containing buffer. TNF-α treatment resulted in deterioration of heart function. HIPC offered better protection by significantly increasing left ventricular developed pressure (Pmax) and coronary flow (P<0.01), and by decreasing left ventricular end-diastolic pressure (P<0.01). NIPC or pretreatment of the hearts with E2 normalized left ventricular end-diastolic pressure, coronary flow and coronary vascular resistance (P<0.001); however, it did not normalize Pmax. The combination of E2 and HIPC did not show any synergetic protection; however, the addition of HIPC normalized Pmax (P<0.001). TNF-α treatment resulted in deterioration of heart hemodynamics, which were reversed by HIPC, E2 PC and pretreatment. The combination of these treatments did not add to the previously observed protection compared with when they were used individually.


Self-reported practices and attitudes of US oncologists regarding off-protocol therapy.
Investigational cancer therapies being tested in clinical trials may be available outside of trials, or off-protocol (OPRx). We evaluated the practices and attitudes among US oncologists with regard to this controversial practice. We mailed an anonymous survey to a random sample of US medical oncologists evaluating frequency and prevalence of OPRx and evaluated the correlation between demographic factors, attitudes, and practice. One hundred forty-six (31%) of 471 oncologists responded. Ninety-three percent reported ever discussing and 81% ever prescribing OPRx. Academic oncologists were more likely than community oncologists to have ever provided OPRx (89% v 75%; P = .06), to discuss OPRx at least once/month (41% v 19%; P = .0004), and to deny requests for OPRx at least once/month (16% v 2%; P = .004). While 61% of oncologists believed that patients should be discouraged from OPRx, only 31% felt it should not be available. With regard to trial recruitment, 53% felt that informed consent requires discussion of OPRx, 34% disagree, and 26% feel that patients should be provided OPRx on request, while 56% disagree. There was lack of consensus on access to OPRx in scenarios based on open trials at the time of the survey, such as adjuvant trastuzumab, which 41% would provide, 59% would not. US oncologists report common discussion and use of OPRx, but attitudes and practices may vary substantially. There is need for greater debate regarding OPRx in oncology, further definition of the ethical and clinical issues at stake, and development of guidelines in this area.


The possible benefits of difficulty: how stress can increase and decrease subjective well-being.
This study explores the effects of stress, trauma, coping and growth orientation on subjective well-being. Based on cognitive stress theory, it was hypothesized that adversity may contribute to increased or decreased well-being, depending on the subsequent meaning these experiences are given. Survey data from Norwegian UN/NATO veterans (N= 142) showed that stress and well-being were negatively associated (r=-0.20, p < 0.05) at the level of zero-order correlations. However, a full structural equation model revealed that the effect of stress on well-being was mediated positively through a problem-focused coping process combined with a growth component. Stress was negatively mediated through an avoidant-focused coping process and a distress component. The effect from stress was fully mediated in the model. The hypothesis that stress can produce both increased and decreased subjective well-being was confirmed.


A discussion of the concept of technology transfer of research-based drug "abuse" prevention and treatment interventions.
With the availability of both drug user prevention and treatment interventions that have demonstrated effectiveness under rigorous experimental design, new avenues of research have opened up to bring these strategies to scale. Of major importance is adapting evidence-based prevention and treatment programs to community specifications without diluting their power. A number of researchers have examined this issue from a variety of perspectives. This brief discussion is an attempt to bring those perspectives together within a conceptual framework that integrates them around research issues and questions. Several theoretical perspectives that have not been brought into the technology transfer discussion are mentioned, others need to be reviewed for their potential to guide further research in this area.


Lack of association between +405 G/C polymorphism in VEGF and breast cancer risk: A meta-analysis.
To explore whether the vascular endothelial growth factor (VEGF) +405 G/C polymorphism confers susceptibility to breast cancer (BC) by conducting a meta-analysis. Publications addressing the association between the VEGF +405 G/C polymorphism and BC risk were selected from the PubMed, Embase and Google Scholar databases. Data were extracted from studies by three independent reviewers. The meta-analysis was performed by STATA 12.0 software, and odds ratio (OR) with 95% confidence interval (CI) were calculated. Finally, 10 case-control studies were retrieved with a total of 8,855 BC patients and 9,393 controls. No significant association was identified between VEGF +405 G/C polymorphism and BC risk in overall populations under 5 models (C vs G: OR=1.001, 95% CI=0.896-1.119, p=0.987; CC vs GG: OR=1.006, 95% CI=0.853-1.186, p=0.997; CG vs GG: OR= 0.985, 95% CI=0.823-1.178, p=0.779; CC vs CGs/GG: OR=1.019, 95% CI=0.921-1.127, p=0.722; CC/CG vs GG: OR=0.985, 95% CI=0.835-1.162, p=0.862), and also in the subgroup analysis by ethnicity. Our study confirms that there is a lack of association between the VEGF +405 G/C polymorphism and BC risk.


Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis.
We used a nested polymerase chain reaction assay to quantitate the number of viral copies in cells of CSF of eight patients with herpes simplex virus encephalitis (HSVE). The viral load was monitored in serial CSF samples during the course of disease and correlated to clinical symptoms, radiologic manifestations, efficacy of acyclovir treatment, and overall clinical outcome. Before treatment, HSV type 1 (HSV-1) copies were detected at a mean value of 1,786/10(5) (range, 5 to 8,333/10(5) cells; median, 81/10(5) cells). During therapy, HSV-1 DNA decreased gradually to a mean value of 6 copies/10(5) cells (range, 0 to 33 copies/10(5) cells; median, 0 copies/10(5) cells) within 6 to 21 days and disappeared or was barely detectable before treatment completion in most cases. The HSV-1 burden in the CSF did not clearly correlate with the severity of clinical signs or the degree of cranial imaging findings and overall outcome. Quantitation of HSV-1 copies allows rapid and reliable monitoring of antiviral therapy. The absence of a clear correlation between viral load in the CSF and morbidity may suggest a role for indirect mechanisms of brain injury in HSVE.


[Effect of recombinant VEGF-C secreted from eukaryotic cells on proliferation and chemotherapy-induced apoptosis of leukemic cells].
Vascular endothelial growth factor-C/vascular endothelial growth factor receptor-2, -3 (VEGF-C/VEGFR-2,3) signaling pathway can induce angiogenesis/lymphangiogenesis, and promote invasion and metastasis of solid tumors. Recent studies showed that VEGF-C and its receptors also expressed on hematological tumor cells, but their effects on leukemic cells are unclear. This study was to explore the effects of recombinant VEGF-C secreted from VEGF-C cDNA-transfected CHO (CHO/VEGF-C) cells on proliferation and chemotherapy-induced apoptosis of leukemic cells. The effect of recombinant VEGF-C (in the supernatants of CHO/VEGF-C cells) on angiogenesis was observed using the chicken chorioallantoic membrane model. The expression of VEGFR-2 and VEGFR-3 on leukemic cell lines TF-1, K562, HEL, NB4, HL-60, MR2, U937,SHI-1, and RPMI8226 was detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM). The effect of VEGF-C on the proliferation of NB4 and K562 cells was assessed by MTT assay; its effect on the apoptosis of NB4 cells, which were treated with chemotherapeutic agents [etoposide (VP-16), daunorubicin (DNR), or arsenic trioxide (As2O3)], was investigated by FCM with Annexin V/PI double staining. The supernatant of CHO/pcDNA3.1 cells was used as control. The recombinant VEGF-C induced angiogenesis in the chicken chorioallantoic membrane model. VEGFR-3 was expressed in NB4, HEL, and RPMI8226 cells; VEGFR-2 was expressed in HEL and TF-1 cells. Compared with the controls, the recombinant VEGF-C promoted the proliferation of NB4 cells (VEGFR-3(+)) (P(24h)=0.006, P(48h)=0.018), but had no effect on K562 cells (VEGFR-3(-)); it inhibited the chemotherapy-induced apoptosis of NB4 cells (P(VP-16)=0.019, P(DNR)=0.013, P(As2O3)=0.042). The recombinant VEGF-C could induce angiogenesis, and may promote the proliferation and inhibit the chemotherapy-induced apoptosis of leukemic cells via VEGFR-3 signaling pathway, which might be potential target therapy for leukemia.


Solution and solid-state studies of doubly trimethylene-bridged tetraalkyl p-phenylenediamine diradical dication conformations.
X-ray crystallographic structures are reported for 1(Me)(2+)(SbCl(6)(-))(2) x 2 CH(3)CN, 2(Et)(2+)(SbF(6)(-))(2) x 2 CH(3)CN x 2 CH(2)Cl(2), and 1(iPr)(2+)(SbF(6)(-))(2), which also contained unresolved solvent and is in a completely different conformation than the methyl- and ethyl-substituted compounds. A quite different structure of 1(Me)(2+)(SbF(6)(-))(2) than that previously published was obtained upon crystallizing it from a mixture rich in monocation. It does not contain close intramolecular PD(+),PD(+) contacts but has close intermolecular ones. Low temperature NMR spectra of 1(Me)(2+) and 1(Et)(2+) in 2:1 CD(3)OD/CD(3)CN showed that both contain three conformations of all-gauche NCCC unit material with close intramolecular PD(+),PD(+) contacts. In addition to the both PD(+) ring syn and anti material that had been seen in the crystal structure of 1(Me)(2+)(SbF(6)(-))(2) x 2 CH(3)CN published previously, an unsymmetrical conformation having one PD(+) ring syn and the other anti (abbreviated uns) was seen, and the relative amounts of these conformations were significantly different for 1(Me)(2+) and 1(Et)(2+). Calculations that correctly obtain the relative amounts of both the methyl- and ethyl-substituted material as well as changes in the optical spectra between 1(Me)(2+) and 1(Et)(2+), which contains much less of the uns conformation, are reported.


A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.
This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains. Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively. The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.1pg/µl of leptospiral DNA and sensitivity of 103 leptospires/ml in both spiked urine and water. Our duplex endpoint PCR assay is suitable for rapid early detection of Leptospira with high sensitivity and specificity.


Patterns of career decision-making difficulties in 16 countries: A person-centered investigation.
Classifying clients into career indecision types can facilitate tailoring interventions to each client's specific needs. The present research examined a typology of career indecision on 50 data sets (N = 31,527) representing diverse populations from 16 countries on five continents. Latent profile analyses of participants' responses on the Career Decision-Making Difficulties Questionnaire (CDDQ) revealed seven replicable career indecision types across samples: unmotivated, unrealistic, generally uninformed, occupations-uninformed, conflicted-uninformed, externally conflicted, and internally conflicted. Age emerged as a negligible predictor of career indecision types, whereas gender predicted membership in the unmotivated type, with men twice more likely to be unmotivated than women. The seven types were similarly predictive of career decision status, decision certainty, and decision self-efficacy. These results largely support using the CDDQ to differentially diagnose career indecision types based on 10 causes of career indecision in different countries, life stages, and genders. Classifying individuals based on their patterns of career decision-making difficulties supports tailoring individual career counseling or group interventions to clients' needs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


[Comparison of two dimensional and three dimensional CBF measurements in stroke patients].
The purpose of this study is to compare the detectability of the reduction in cerebral blood flow (CBF) using the two versus the three dimensional technique of CBF measurement. Both techniques were simultaneously carried out 85 times on 52 stroke patients. In the two dimensional technique, CBF was measured by the Xe-133 inhalation method and the value was calculated by the initial slope index. In the three dimensional technique, CBF was measured by single photon emission CT with Xe-133 inhalation method. CBF reduction was studied in the middle cerebral artery (MCA) territory on a CBF map in both techniques. Additionally, mean CBF was also calculated for the same territory. On the CBF map, the CBF reduction was shown in 25 of 85 measurements with the two dimensional technique and in 41 of 85 with the three dimensional technique. In comparing the imagings of both techniques, the CBF reduction seen extensively along the cortical surface and in the entire MCA territory with the three dimensional technique was also detected with the two dimensional technique. However, focal CBF reduction observed at the cortical surface and in the deep cerebral tissue with the three dimensional technique was not detected with the two dimensional technique. In order to evaluate both techniques quantitatively, we calculated the ratio of the mean CBF difference between the MCA territories of both hemispheres to mean CBF in the non-affected MCA territory. This ratio represented the asymmetry index. Firstly, the relationship between asymmetry index and the imaging of CBF reduction on the CBF map was studied.(ABSTRACT TRUNCATED AT 250 WORDS)


Extraordinary infrared transmission through a periodic bowtie aperture array.
The discovery of extraordinary transmission through periodic aperture arrays has generated significant interest. Most studies have used circular apertures and attributed enhanced transmission to surface plasmon polariton (SPP) resonances and/or Rayleigh-Wood anomalies (RWA). Bowtie apertures concentrate light and have much longer cutoff wavelengths than circular apertures and can be designed to be strongly resonant. We demonstrate here that the total transmission through a bowtie aperture array can exceed 85% (4x the open area). Furthermore, we show that the high transmission is due to waveguide modes as opposed to the commonly believed SPP/RW phenomena. This work is focused on IR wavelengths near 9 microm; however, the results are broadly applicable and can be extended to optical frequencies.


Co-constructing a cross-cultural course: resisting and replicating colonizing practices.
This article examines the cross-cultural complexities of teaching and learning processes at different levels in a family therapy training program delivered in a different country. It presents two interlinked narratives of an advanced family therapy training program delivered in Slovenia by a U.K-based family therapy training institute. The context in which the training was negotiated and planned is discussed, highlighting issues at the macrosystemic level. Dilemmas that arose in relation to differing beliefs about teaching and learning are elaborated. We examine power relationships, ways that we positioned ourselves and each other, and how we tried and sometimes failed to take these into account. We question how the issue of spoken language and its meanings creates its own constraints and power structures, and how we respond to the impossibilities of translation. We argue that it is through the examination of uncomfortable processes that we develop self-reflexivity and work toward more equitable relationships.


Evidence for a role of opioid peptides in the release of arginine vasopressin in the conscious rat.
Recent reports have suggested that opioid peptides may be involved in renal water excretion. The present in vivo experiments, therefore, were undertaken to determine the effect of opioid peptides on the osmotic and nonosmotic release of arginine vasopressin (AVP) in the conscious rat. Experimental animals were infused intravenously with naloxone (20 mug/kg per min) or oxilorphan (40 mug/kg per min), chemically dissimilar opioid antagonists. Control rats were infused with normal saline, the vehicle for the opioid antagonists. In all three groups the osmotic release of AVP was examined during an acute hypertonic saline (3%) infusion (2 ml/100 g body wt). The antidiuresis following the hypertonic saline infusion was significantly attenuated in naloxone- and oxilorphan-treated rats, as the peak urinary osmolality (Uosm) rose to 581.4+/-22.4 and 558.2+/-27.6 mosmol/kg H(2)O in naloxone- and oxilorphan-treated rats as compared with the value in control rats of 735.3+/-24.2 mosmol/kg H(2)O (both P < 0.001 vs. control). At the same time the plasma AVP levels of 5.4+/-1.3 and 5.2+/-1.1 pg/ml in naloxone- and oxilorphan-treated rats, respectively, were significantly lower than the plasma AVP in control rats of 16.9+/-2.5 pg/ml (P < 0.001). In another three groups of rats the nonosmotic release of AVP was examined during hypovolemia induced by intraperitoneal 6% dextran (1.8 ml/100 g body wt). Following intraperitoneal administration of dextran the peak Uosm of 703.0+/-87.8 and 734.8+/-99.1 mosmol/kg H(2)O in naloxone- and oxilorphan-treated rats, respectively, was significantly less than the value in control rats of 1,169.3+/-135.5 mosmol/kg H(2)O (both P < 0.02 vs. control). A comparable decrease in blood volume of 13% occurred in all three groups of animals. During the dextran administration plasma AVP levels in naloxone- and oxilorphan-treated rats increased to 4.3+/-1.0 and 6.0+/-2.0 pg/ml, respectively; both of these values were significantly lower than the plasma AVP of 12.9+/-1.4 pg/ml in control rats (P < 0.02). The effect of opioid antagonists to impair the osmotic and nonosmotic release of AVP occurred in the absence of differences in mean arterial pressure, glomerular filtration rate and the renal response to AVP. These results, therefore, indicate that opioid peptides are involved in renal water excretion primarily by modulating the central release of AVP.


Effects of the Pimelic Diphenylamide Histone Deacetylase Inhibitor HDACi 4b on the R6/2 and N171-82Q Mouse Models of Huntington's Disease.
This report represents a detailed description of experiments designed to replicate and extend the findings of a published study on the effects of treating the R6/2 Huntington's disease (HD) mouse model with ~300 CAG repeats using the pimelic diphenylamide histone deacetylase (HDAC) inhibitor, HDACi 4b (Thomas et al., 2008). In addition to testing the R6/2 mice, similar experiments examined the effects of the drug on a second transgenic HD mouse model, the N171-82Q mice. As in the original study, the drug was delivered in the drinking water. In the present study we tested larger groups of mice than in the original study. The results indicated that we were unable to replicate the significant behavioral effects of oral HDACi 4b treatment in the R6/2 mice. There were however, non-significant trends for the treated R6/2 mice to be less affected on some of the measures and there were instances of phenotype progression being delayed in these treated mice. In contrast, we did replicate the protection from striatal atrophy in the R6/2 mice. We also did not observe any beneficial effects of HDACi 4b treatment in the N171-82Q mice. Although the behavioral procedures were replicated and an automated activity assessment was added, there were several unexpected complications in terms of solubility of the drug, CAG repeat length differences and gender differences in progression of the phenotype that could have affected outcomes. Clearly more studies will have to be performed using other methods of delivery as well as assessing effects in more slowly progressing HD models to better evaluate the effects of this HDAC inhibitor.


Feasibility Study for Detection of Turnip yellow mosaic virus (TYMV) Infection of Chinese Cabbage Plants Using Raman Spectroscopy.
Raman spectroscopy provides many advantages compared to other common analytical techniques due to its ability of rapid and accurate identification of unknown specimens as well as simple sample preparation. Here, we described potential of Raman spectroscopic technique as an efficient and high throughput method to detect plants infected by economically important viruses. To enhance the detection sensitivity of Raman measurement, surface enhanced Raman scattering (SERS) was employed. Spectra of extracts from healthy and Turnip yellow mosaic virus (TYMV) infected Chinese cabbage leaves were collected by mixing with gold (Au) nanoparticles. Our result showed that TYMV infected plants could be discriminated from non-infected healthy plants, suggesting the current method described here would be an alternative potential tool to screen virus-infection of plants in fields although it needs more studies to generalize the technique.


Comparison of Multi-Fiber Reproducibility of PAS-MRI and Q-ball With Empirical Multiple b-Value HARDI.
Crossing fibers are prevalent in human brains and a subject of intense interest for neuroscience. Diffusion tensor imaging (DTI) can resolve tissue orientation but is blind to crossing fibers. Many advanced diffusion-weighted magnetic resolution imaging (MRI) approaches have been presented to extract crossing-fibers from high angular resolution diffusion imaging (HARDI), but the relative sensitivity and specificity of approaches remains unclear. Here, we examine two leading approaches (PAS and q-ball) in the context of a large-scale, single subject reproducibility study. A single healthy individual was scanned 11 times with 96 diffusion weighted directions and 10 reference volumes for each of five b-values (1000, 1500, 2000, 2500, 3000 s/mm2) for a total of 5830 volumes (over the course of three sessions). We examined the reproducibility of the number of fibers per voxel, volume fraction, and crossing-fiber angles. For each method, we determined the minimum resolvable angle for each acquisition. Reproducibility of fiber counts per voxel was generally high (~80% consensus for PAS and ~70% for q-ball), but there was substantial bias between individual repetitions and model estimated with all data (~10% lower consensus for PAS and ~15% lower for q-ball). Both PAS and q-ball predominantly discovered fibers crossing at near 90 degrees, but reproducibility was higher for PAS across most measures. Within voxels with low anisotropy, q-ball finds more intra-voxel structure; meanwhile, PAS resolves multiple fibers at greater than 75 degrees for more voxels. These results can inform researchers when deciding between HARDI approaches or interpreting findings across studies.


[Estimation and valuation of the hygienic quality of fodder for swine].
The feeding value of feedstuffs does not only depend on the nutrient contents but also on the hygienic quality of the ration. The hygienic state of feedstuffs can be characterized by observations in the sensorial examination, by dry matter contents, by the species and number of germs, by toxin contents and by the quantity of destructive insects. Lacks of hygienic quality generally produce non-specific symptoms in animals with few exceptions only (for example: zearalenone----hyperoestrogenic effects), or they just lead to a reduced performance. The veterinarian practitioner can get first and essential informations concerning the hygienic state of feedstuffs by critical sensorial examination of the feedstuffs. If there are doubts, feed samples should be sent to a specialized institute for further investigations. Actually observed lacks of hygienic quality of feedstuffs for pigs are demonstrated and discussed. It is the aim of this contribution to focus the practitioners attention on lacks of hygienic quality of feedstuffs and their potential consequences for health and performance of pigs.


Importance of Computed Tomography in Determining Displacement in Scaphoid Fractures.
Background Displaced scaphoid fractures have a relatively high rate of nonunion. Detection of displacement is vital in limiting the risk of nonunion when treating scaphoid fractures. Questions/Purpose We evaluated the ability to diagnose displacement on radiographs and computed tomography (CT), hypothesizing that displacement is underestimated in assessing scaphoid fracture by radiograph compared with CT. Materials and Methods Thirty-five preoperative radiographs and CT scans of acute scaphoid fractures were evaluated by two blinded observers. Displacement and angular deformity were measured, and the fracture was judged as displaced or nondisplaced. Scapholunate, radiolunate, and intrascaphoid angles were measured. Radiograph and CT measurements between nondisplaced and displaced fractures were compared. Intraobserver reliability was measured. Results Reader 1 identified 12 fractures as nondisplaced on radiograph, but displaced on CT (34%). Reader 2 identified 9 fractures as nondisplaced on radiograph, but displaced on CT (26%). For displaced fractures, the mean intrascaphoid angle was over three times greater when measured on CT than on radiograph (56 vs. 16 degrees). Scapholunate angle >65 degrees and radiolunate angle >16 degrees were significantly associated with displacement on CT. Interobserver reliability for diagnosing displacement was perfect on CT but less reliable on radiograph. Conclusion Scaphoid fracture displacement on CT was identified in 26 to 34% of fractures that were nondisplaced on radiograph, confirming that radiographic evaluation alone underestimates displacement. These results underscore the importance of CT scan in determining displacement and angular deformity when evaluating scaphoid fractures, as it may alter the decision on treatment and surgical approach to the fracture. We recommend considering CT scan to evaluate all scaphoid fractures. Level of Evidence Level III.


Student and instructor perspectives following a virtual objective structured clinical examination.
In March 2020, COVID-19 public health restrictions impeded in-person clinical assessment. In response, a dental hygiene program administered a virtual objective structured clinical exam (vOSCE) using Zoom to assess student competency in performing a health history. This study aimed to explore the vOSCE experience from both student and clinical instructor perspectives. This 2-part cross-sectional study gathered student and clinical instructor perceptions of the vOSCE. Forty-two students were invited to complete an online questionnaire. Basic descriptive statistics reporting percentages were tabulated. Twelve clinical instructors were invited to participate in focus groups, which were audiorecorded and transcribed verbatim. Qualitative data were analysed using inductive thematic analysis. Questionnaires were received from 23 (55%) students. Students supported (91%) the vOSCE experience and believed it assessed their knowledge (87%), their ability to complete a health history (91%), and ability to communicate effectively (87%). Students reported high agreement (87%) with how the Zoom platform facilitated the examination. Some students (35%) felt the vOSCE was more stressful than an in-person OSCE. However, 43% indicated it wasn't more stressful. Focus groups with clinical instructors revealed perspectives on using vOSCEs, which were captured under 4 themes: preparation, assessment suitability, authenticity, and future considerations. Based on student and instructor perspectives, vOSCEs could be a viable alternative to in-person OSCEs for health history evaluations. As technology applications continue to emerge for conducting virtual examinations, there may be increased use of and ease of use with a virtual platform to conduct other types of clinical evaluations.


Ins(3,4,5,6)P4 specifically inhibits a receptor-mediated Ca2+-dependent Cl- current in CFPAC-1 cells.
We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4] in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had no effect on basal current, but it produced a five- to sevenfold reduction in the Cl- current stimulated by either 2 microM extracellular ATP or by 1 microM extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P4 was 2.9 microM, and 4 microM blocked >80% of the ATP-activated current. In contrast, 10 microM Ins(1,4,5,6)P4, Ins(1,3,4,5)P4, or Ins(1,3,4,6)P4 enhanced rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P4 only acted transiently. These stimulatory effects were Ca2+ dependent and largely inhibited by coapplication of equimolar Ins(3,4,5,6)P4. Inositol 1,3,4,5,6-pentakisphosphate, the precursor of Ins(3,4,5,6)P4, did not affect Cl- current. These data consolidate and extend the hypothesis that Ins(3,4,5,6)P4 is an important intracellular regulator of Cl- current in epithelial cells.


Glucagon-insulin balance in genetically lean or fat chickens.
Circulating levels of insulin, glucagon, glucose and non-esterified fatty acids (NEFA) were compared in genetically lean (LL) or fat (FL) lines of chickens between 5 and 6 weeks of age. FL birds exhibited lower levels of plasma glucose and higher levels of NEFA when fasted or fed; however no genotypic differences were found for insulin or glucagon. Oral glucose tolerance test induced higher insulin concentrations in FL chickens with faster glucose tolerance whereas glucagon was similar between genotypes. Refeeding led to lower plasma glucose and insulin in FL chickens but similar levels of glucagon in both lines. Exogenous insulin (0.25 or 0.50 U/kg) had less hypoglycemic effects but induced higher levels of glucagon in fasted LL chickens at 0.50 U. The insulin to glucagon ratio cannot explain differences in fattening between genotypes. Lipolysis is slightly higher in FL chickens. A difference between the 2 genotypes for their glucose-insulin balance is probably the main mechanism involved.


Serological evidence of exposure to tick-borne agents in opossums (Didelphis spp.) in the state of São Paulo, Brazil.
This work involved a serological investigation of tick-borne pathogens in opossums in eight municipalities of the state of São Paulo, Brazil. Serum samples from 109 opossums (91 Didelphis aurita and 18 Didelphis albiventris) were tested to detect antibodies to Rickettsia rickettsii (Taiaçu strain, 1:64 cut-off) and Ehrlichia canis (São Paulo strain, 1:40 cut-off), by indirect immunofluorescence assay (IFA); and against Borrelia burgdorferi (strain G39/40) by enzyme-linked immunosorbent assay (ELISA). The presence of antibodies to anti-R. rickettsii, anti-E. canis and anti-B. burgdorferi was detected in 32 (29.35%), 16 (14.67%) and 30 (27.52%) opossums, respectively. Opossum endpoint titers ranged from 64 to 1,024 for R. rickettsii, from 40 to 160 for E. canis, and from 400 to >51,200 for B. burgdorferi. These serological results suggest that opossums have been exposed to Rickettsia spp., Ehrlichia spp., and B. burgdorferi-related agents in the state of São Paulo. Our study underscores the need for further research about these agents in this study area, in view of the occurrence of Spotted Fever and Baggio-Yoshinari Syndrome disease in humans in the state of São Paulo, Brazil.


Abiesatrines A-J: anti-inflammatory and antitumor triterpenoids from Abies georgei Orr.
A novel spiro-lanostane (abiesatrine A, 1) was isolated from the aerial parts of Abies georgei together with 9 new (abiesatrines B-J, 2-10) and 10 known triterpenes (11-20). The new structures were established by the extensive analysis of their spectroscopic data. The configuration of 1, featuring a unique spirolactone formed by C-13 and C-23 via oxygen-bridge, was confirmed by X-ray crystallography, and its biopathway was tentatively proposed. Among these isolates, compound 16 showed the strongest inhibitory activity against LPS-induced NO production in RAW264.7 macrophages (IC(50) = 8.9 microg mL(-1)). While compounds 1 and 20 exhibited potent anti-proliferative effects on QGY-7703 cells with IC(50) values of 9.3 and 7.6 microg mL(-1), respectively. Preliminary structure-activity relationship (SAR) investigations defined structural feature of the 24Z-olefinic bond key to the lanostane and cycloartane pharmacophore.


Differentiation of thyroid nodules using Tl-201 scintigraphy quantitative analysis and fine-needle aspiration biopsy.
We studied the differentiation of thyroid nodules using fine-needle aspiration biopsy (FNA) and Tl-201 scintigraphy quantitative analysis. One-hundred and thirty-one thyroid nodules were examined: 83 follicular lesions (58 benign and 25 malignant lesions) and 48 non-follicular lesions (8 benign and 40 malignant lesions). During Tl-201 scintigraphy examinations, an early and a delayed image were acquired 10 and 120 min after an intravenous injection, respectively. The T/N ratio (counts of nodular lesion/counts of contralateral normal thyroid tissue) of each image was calculated quantitatively. We assessed the ability of the Tl-201 scintigraphy and of the FNA analysis to differentiate benign and malignant lesions and determined the cut-off levels for the assays. For the follicular lesions, the area under the ROC (Receiver Operating Characteristic) curve (Az) for the Tl-201 scintigraphy data was greater than that for the FNA data. For the non-follicular lesions, the Az for the FNA data was greater than that for the Tl-201 scintigraphy data. We set cut-off levels at 1.370 for follicular lesions, and 1.070 for non-follicular lesions. The sensitivity and specificity were 76% and 82.7% for follicular lesions, and 90% and 87.5% for non-follicular lesions, respectively. The overall accuracy of the analysis was 84.0%.


Utilisation and barriers of PoCUS in a rural emergency department - A quality improvement project.
Point-of-care ultrasound (PoCUS) has been recognised as a tool that leads to more definitive diagnoses and enhances clinical decision-making in rural emergency departments (EDs) where diagnostic imaging is limited. We aimed to determine the current utilisation, barriers and solutions to using PoCUS in this rural Saskatchewan ED. Physicians working in the ED participated in a semi-structured interview. An online survey, administered via SurveyMonkey post-interview to provide further context, was used to support qualitative approaches. Interviews were recorded, transcribed and then analysed using inductive interpretation. Seven physicians completed the quantitative survey with a response rate of 70%. Ten physicians were interviewed with a response rate of 100%. Themes identified were that physicians in this community's ED perceived their skill level as determining whether a scan was diagnostic or not, rather than the specific PoCUS application itself. In addition, they performed scans primarily for the purpose of triage. Inadequate training, Core IP certification certification requirement and intradepartmental logistics were barriers to PoCUS utilisation. This study showed that ED physicians in this community perceived PoCUS as a clinical adjunct and as a tool to triage patients for further imaging. Results highlight the need to have accessible training for rural physicians to increase PoCUS utilisation, awareness of current Saskatchewan PoCUS guidelines and education on diagnostic applications of PoCUS. Increased use of PoCUS for specific scans could decrease the need for formal imaging and the associated healthcare system resources.


Evaluation of photobiomodulation for postoperative discomfort following laser-assisted vital pulp therapy in immature teeth: A preliminary retrospective study.
Minimally invasive endodontics is recommended for young, immature teeth to preserve healthy pulp and dentin tissue. The aim of the study was to examine the cold sensitivity of immature teeth that received photobiomodulation (PBM) after vital pulp therapy (VPT). The study followed the STROBE guidelines and included 123 healthy patients aged 8-13. The immature teeth (incisors, premolars and molars) that qualified for VPT received the bioceramic material - Biodentine. In this experiment, teeth were treated immediately and at 24 h post-VPT with a 635-nm diode laser using a power of 100 mW, a power density of 200 mW/cm2 and a total energy of 4 J (PBM group, n = 43), while those not treated were the control group (n = 43). The tooth sensitivity to cold was measured using a visual analogue scale (VAS) before and at 6 h, 1 day, 7, 30, and 90 days after treatment. The predictor variable was PBM skills regarding the ability to decrease cold sensitivity after VPT. The primary endpoint was the time to reverse hypersensitivity to cold, and the secondary endpoint was the occurrence of possible side effects. The Mann-Whitney U test, Friedman test along with Dunn's post hoc test, and the χ2 test were used to investigate tooth sensitivity. Eighty-six immature permanent teeth of 86 children were included in the study. It was shown that the difference was significant for sensitivity to a cold stimulus between the groups at 6 h, 24 h, 7 days, and 30 days, but no difference was found preoperatively and at 90 days (6 h, 24 h, 7 days, and 30 days, p < 0.001, and 90 days, p = 0.079). However, patients in both groups reported a decrease in discomfort provoked by cold stimuli throughout the follow-up period. Photobiomodulation decreased postoperative sensitivity and was more acceptable for patients. Further randomized clinical studies with placebo-controlled groups are needed.


Metabolic syndrome & psychiatric disorders.
The metabolic syndrome, a constellation of symptoms associated with obesity, dyslipidaemia, insulin insensitivity, deranged glucose metabolism and hypertension has been gaining widespread interest due to its immense clinical relevance. We review the metabolic syndrome in terms of its diagnostic criteria and its relationship with severe mental illnesses and psychotropic medications, and the guidelines to manage it.


Density functional study of the oxidation of small neutral and charged silver clusters.
We have studied the energetic and structural stability of the interaction of molecular oxygen with small neutral, anionic and cationic silver clusters, Ag(n) (3 < or = n < or = < 8). The calculations have been carried out using a linear combination of atomic Gaussian-type orbitals within the density functional theory as it is implemented in the demon-ks3.5 code. The O2 molecule has been placed in different positions surrounding the cluster, in order to increase the configurational space of the structural minima. We have found that the oxidized cation and neutral clusters undergo a 2D-3D structural transition even before than the nonoxidized counterparts. Moreover, our results show that the adsorption energies on the cationic and neutral silver oxide clusters manifest an odd-even alternation pattern. Likewise, the average magnetic moment of the O2 radical in the charged and neutral silver environment tends to be greater than the charged and neutral bare diatomic oxygen molecule.


A survey of Babesia spp. and Hepatozoon spp. in wild canids in Israel.
Babesia spp. and Hepatozoon spp. are apicomplexan parasites that infect a variety of animals, including canids. Their life-cycle includes an invertebrate hematophagous vector as a definitive host and vertebrates as intermediate hosts. The aims of this study were to investigate the prevalence and risk factors for Babesia spp. and Hepatozoon spp. infections in wild golden jackals (Canis aureus) and red foxes (Vulpes vulpes) in Israel and to compare spleen with blood sample polymerase chain reaction (PCR) for the detection of infection. Blood and spleen samples from 109 golden jackals and 21 red foxes were tested by PCR for the detection of Babesia spp. and Hepatozoon spp. using primers for the 18S ribosomal (r) RNA gene. Hepatozoon canis was detected in 50/109 (46%) of the jackals and 9/21 (43%) of the foxes. "Babesia vulpes" (the Babesia microti-like piroplasm) was detected in 4/21 (19%) of the foxes and in none of the jackals. A previously unknown genotype termed Babesia sp. MML related to Babesia lengau (96-97% identity) was detected in 1/109 (1%) of the jackals and 4/21 (19%) of the foxes. Further characterization of this genotype carried out by PCR of the rRNA internal transcribed spacer 2 (ITS2) indicated that it had only 87% identity with the B. lengau ITS2. Sex (male or female), age (juvenile or adult) and geographic zone (North, Central or South Israel) were not found to be significant risk factors for these protozoan infections. The prevalence of "B. vulpes" and Babesia sp. MML infections was significantly higher in foxes compared to jackals (χ2 = 15.65, df = 1, P < 0.005), while there was no statistically significant difference in the rate of H. canis infection between these two canid species. A fair agreement beyond chance between identification in the blood and spleen of H. canis was found in 21 animals from which both blood and spleen samples were available (k = 0.33). This study describes a high prevalence of H. canis infection in foxes and jackals and is the first report of "B. vulpes" infection in Israel, an area where Ixodes spp. are rare. It describes infection with a previously unknown genotype of Babesia related to B. lengau from Africa.


Managing a good death in critical care: can health policy help?
This paper discusses end-of-life care (EoLC) in critical care through exploration of what is known from the international literature and what is currently presented within UK policy. EoLC is an important international critical care issue, and currently provides a key focus for health care policy in the UK. While society holds that critical care is delivered in a highly technical area with a strong focus on cure and recovery, mortality rates in this speciality remain at approximately 20%. When patient recovery is not an outcome, discussions with patient, family and extended care teams turn towards futility of treatment and end-of-life management. However, there are specific barriers to overcome in EoLC for the critically ill. A key issue for EoLC in critical care is a lack of robust systems to prospectively identify individuals who are most at risk of dying. A further challenge is divergent perspectives within and across clinical teams on treatment withdrawal and limitation practices. To streamline patient management and underpin a hospice approach to care, EoLC policies are currently being used within the UK. While this provides a national framework to address some key critical care clinical issues in the UK, there is a need for further refinement of the tool to reflect the reality of EoLC for the critically ill. It is important that international best practice exemplars are examined and clinicians actively engage and contribute to ensure that any local EoLC frameworks are fit for purpose.


The Fentanyl Epidemic and Evolution of Fentanyl Analogs in the United States and the European Union.
Since 2013, an unprecedented surge in fentanyl overdose deaths has been caused by heroin laced with illicitly produced fentanyl and/or fentanyl analogs (FAs) sold as heroin. The US Drug Enforcement Agency's National Forensic Laboratory Information System reported a >300% increase in fentanyl encounters from 4697 in 2014 to 14440 in 2015. In 2015, the CDC reported 9580 deaths caused by synthetic opioids, primarily fentanyl, a 72% increase from 2014. The European Monitoring Centre for Drugs and Drug Addiction has also encountered several new FAs in the heroin supply. Counterfeit pharmaceuticals containing mixtures of fentanyl and FAs continue to be a poorly recognized worldwide problem despite the WHO classifying several FAs as a serious threat to public health. This review covers the epidemiology of fentanyl abuse and discusses the clinical practice implications of widespread fentanyl abuse. It includes a historical perspective on the illicit FAs that have appeared in the US and European Union and reviews the methods available to identify FAs and emerging technologies useful for identifying previously undescribed analogs. A compilation of structural and mass spectral data on FAs reported thus far is provided. Fentanyl and FAs have evolved into a global public health threat. It is important to understand the analytical, clinical, and regulatory efforts underway to assist communities affected by the current fentanyl epidemic.


Late outcomes after the Cox maze IV procedure for atrial fibrillation.
The Cox maze IV procedure (CMPIV) has been established as the gold standard for surgical ablation; however, late outcomes using current consensus definitions of treatment failure have not been well described. To compare to reported outcomes of catheter-based ablation, we report our institutional outcomes of patients who underwent a left-sided or biatrial CMPIV at 5 years of follow-up. Between January 2002 and September 2014, data were collected prospectively on 576 patients with AF who underwent a CMPIV (n = 532) or left-sided CMPIV (n = 44). Perioperative variables and long-term freedom from AF, with and without AADs, were compared in multiple subgroups. Follow-up at any time point was 89%. At 5 years, overall freedom from AF was 93 of 119 (78%), and freedom from AF off AADs was 77 of 177 (66%). No differences were found in freedom from AF, with or without AADs, at 1, 2, 3, 4, and 5 years for patients with paroxysmal AF (n = 204) versus with persistent/longstanding persistent AF (n = 305), or for those who underwent standalone versus a concomitant CMP. Duration of preoperative AF and hospital length of stay were the best predictors of failure at 5 years. The outcomes of the CMPIV remain good at late follow-up. The type of preoperative AF or the addition of a concomitant procedure did not affect late success. The results of the CMPIV remain superior to those reported for catheter ablation and other forms of surgical AF ablation, especially for patients with persistent or longstanding AF.


Use of Tranexamic Acid in Aesthetic Surgery: A Retrospective Comparative Study of Outcomes and Complications.
Bleeding is a potential complication of aesthetic surgery. Surgeons have adhered to the principle of minimizing blood loss. Tranexamic acid (TXA) is an antifibrinolytic medication capable of reducing bleeding. This study aimed to investigate TXA and its effect on complications and overall outcomes in aesthetic surgery patients. This retrospective chart review of patients undergoing various aesthetic procedures between 2019 and 2022 was conducted in Riyadh, Saudi Arabia. Preoperative and postoperative hemoglobin levels, blood transfusions, and complications were the primary outcomes. Furthermore, the predictors of giving TXA were studied. In total, 435 patients were included in the study. TXA was administered to 181 patients (41.6%). Significantly higher proportions of patients who received TXA underwent trunk aesthetic surgery (P < 0.001), and those who received TXA underwent combined procedures more frequently than non-users (P < 0.001). The mean operative time and length of hospital stay were significantly longer among patients who did not receive TXA (P < 0.001, and P < 0.001, respectively). Most predictors for using TXA were significantly associated with performing liposuction (OR = 5.5), trunk aesthetic surgery (OR = 4.9), and undergoing combined procedures (OR = 2.7). No significant difference was noted in the rate of complications between the two cohorts. Although our data show improvement in patient outcomes in multiple aspects, the heterogeneity of our cohort makes us unable to draw definite conclusions to recommend the use of TXA in aesthetic surgery. Thus, a randomized controlled trial is necessary to support the findings of this study.


Bridging the gap: an integrated paediatric to adult clinical service for young adults with kidney failure.
Transition from paediatric to adult care of young adults with chronic diseases is poorly coordinated, often delayed, and usually managed through a single referral letter. About 35% of young adults lose a successfully functioning kidney transplant within 36 months of transfer from paediatric to adult services. Before and after study of the impact of a new integrated paediatric-adult clinical service for patients with kidney failure. Adult renal centre in Oxford and two paediatric renal centres in London. An integrated paediatric-young adult joint transition clinic and care pathway was established in 2006, in conjunction with a young adult clinical service with regular community based clinics. Previously, young adult transplant recipients were transferred by a single referral letter to an adult renal consultant and managed in a conventional adult clinic. Rates of acute rejection and loss of kidney transplants five years before and five years after the introduction of the integrated young adult care pathway. EFFECTS OF THE CHANGE: Nine young adult kidney transplant recipients were transferred directly to adult care between 2000 and 2006 (group 1). From 2006 to 2010, 12 young adult transplant recipients underwent integrated transition into the new young adult service (group 2). Six transplants were lost in group 1 (67%) compared with no transplant losses in group 2. Implementing an integrated transition clinic, coupled with improving young adults' healthcare experience through a young adult clinic, improved patient adherence to regular medication and engagement with healthcare providers, as judged by reduced transplant failure rates. This model may be applicable to other young adult populations with chronic disease transferring to adult healthcare.


Proxy WHO Disability Assessment Schedule 2.0 Is Clinically Useful for Assessing Psychosocial Functioning in Severe Mental Illness.
This study explores how well the World Health Organization Disability Assessment Schedule (WHODAS 2.0) assesses problems with psychosocial functioning in patients with severe mental illness (SMI). Further, we assessed the relationships between psychosocial functioning and psychopathology, medication side effects, treatment setting, and quality of life. We performed an observational, cross-sectional study on the island of Curaçao to assess psychosocial functioning in 77 patients with SMI; they mainly had psychotic disorders. We interviewed their healthcare providers using the proxy version of the WHODAS 2.0. In addition, patients were examined for psychiatric symptoms, medication side effects (including drug-induced movement disorders), and quality of life. Associations were examined with Spearman's rank correlation (ρ). Difficulties in psychosocial functioning were reported by patients with SMI in the WHODAS 2.0 domains of understanding and communicating [mean (M)=34.5, standard deviation (SD)=18.6), participation in society (M=25.5, SD=15.6), and getting along with people (M=24.1, SD=16.1)]. Notably, outpatients had more problems participating in society than inpatients (M=33.6, SD=18.5 versus M=23.2, SD=14.1, p=0.03). A positive correlation was observed between drug-induced parkinsonism and the WHODAS 2.0 total score (ρ =0.30; p=0.02), as well as with various subscales, getting around, and household activities. The proxy version of the WHODAS 2.0 is clinically useful for patients with severe mental illness. The highest scores on the WHODAS 2.0 were found in domains related to interactions with other people and to participation in society. Inpatient status appeared to aid participation in society; this might be due to living in the sheltered clinic environment and its associated daily activities. We further found that drug-induced parkinsonism was associated with a broad spectrum of psychosocial disabilities. ClinicalTrials.gov, identifier: NCT02713672; retrospectively registered in February 2016.


The applicability of the Lamendin method to skeletal remains buried for a 16-year period: a cautionary note.
The Lamendin method is widely reported as one of the most reliable means of age estimation of skeletal remains, but very little is known concerning the influence of burial in soil. This study aimed at verifying the reliability of the Lamendin method on corpses buried for 16 years in a cemetery. The Lamendin and the Prince and Ubelaker methods were applied. In all age groups except the 40- to 49-year-olds, the error was higher in the buried sample. The age-at-death error ranged between 10.7 and 36.8 years for the Lamendin method (vs. the reported 7.3-18.9 years) and 9.5 and 35.7 for the Prince and Ubelaker one (vs. the original 5.2-32.6 years); in all age groups, the error is closer to that found on archeological populations. These results suggest caution in applying the Lamendin method to forensic cases of human remains buried even for a brief period under soil.


Ehrlichia spp. infection in rural dogs from remote indigenous villages in north-eastern Brazil.
Ehrlichia canis is a tick-borne bacterium that causes severe, life-threatening disease in dogs, being more prevalent in tropical and subtropical countries. Randomized studies conducted in Brazil indicate that the prevalence of E. canis infection in dogs ranges from 0.7% to over 50.0%. In a study conducted in northern Brazil, the prevalence was higher in dogs from urban areas, as compared to dogs from rural areas. In the present study, we investigated the exposure to Ehrlichia spp. infection in dogs from remote indigenous villages located in a rural area in north-eastern Brazil. From March to June 2015, 300 privately owned dogs were blood sampled and tested by a rapid ELISA and by a conventional PCR in order to detect anti-Ehrlichia spp. antibodies and E. canis DNA, respectively. Additionally, dogs were also tested for anti-Anaplasma spp. antibodies and Anaplasma platys DNA, using the same diagnostic approaches. Positivity was correlated with tick infestation and dogs' data (gender, age and level of restriction). Overall, 212 (70.7%) dogs were positive for at least one test targeting Ehrlichia spp. In particular, 173 (57.7%) dogs were positive only by rapid ELISA, 5 (1.7%) only by PCR and 34 (11.4%) were simultaneously positive by both tests. In the same way, 39 (13.0%) dogs presented detectable E. canis DNA in their blood, whereas 18 (6.0%) dogs were A. platys DNA-positive. Coupling serological and PCR data, 63 (21.0%) dogs were simultaneously positive to Ehrlichia spp. and Anaplasma spp. Positivity rates for both Ehrlichia spp. and Anaplasma spp. were higher among dogs more than 1 year of age. Sick dogs were more positive to Ehrlichia spp. as compared to healthy dogs. Dogs from rural areas in north-eastern Brazil are highly exposed to Ehrlichia spp. infection and positivity rates do not necessarily correlate with current tick infestation load, since only one infected tick bite is needed to get the infection. This reinforces the importance of keeping dogs free of ticks, in order to reduce as much as possible the risk of infection by E. canis and other tick-borne pathogens such as Babesia vogeli, which are usually co-endemic.


Review of the career of Professor Dr. Herbert Remmer.
This article is a laudatio summarizing the scientific career and accomplishments of Herbert Remmer as observed by one of his first students. The article traces over fifty years of multiple contributions of Herbert Remmer to pharmacology and toxicology and clearly identifies the leadership characteristics of this memorable man.


Presence of a dedicated trauma center physiatrist improves functional outcomes following traumatic brain injury.
Maximizing long-term recovery following traumatic brain injury (TBI) is an important end point. We hypothesized that the addition of a dedicated physiatrist specializing in brain injury medicine to the trauma team would lead to improved functional outcomes. Data from the Northern NJ TBI Model Systems were queried for all patients admitted to rehabilitation from four regional trauma centers, one with a full-time TBI physiatrist (PHYS) and three without (NO-PHYS). Patient demographics, mechanism of injury, Glasgow Coma Scale (GCS) score, length of posttraumatic amnesia, length of stay, and Functional Independence Measure (FIM) were abstracted. TBI severity was determined by GCS score and length of posttraumatic amnesia. FIM motor and cognitive scores at rehabilitation admission and discharge were the primary outcome measure. TBI medications (stimulants, sleep, and neurodepressants) administered in acute care were reviewed to evaluate prescription patterns. A total of 148 patients treated at four trauma centers and discharged to a single acute inpatient rehabilitation center between 2005 to 2013 were divided into two groups, PHYS with 44 patients and NO-PHYS with 104 patients. Compared with those in the NO-PHYS group, patients from the PHYS group had significant improvement in FIM motor and cognitive scores (p < 0.05). Prescription patterns differed. Patients from the PHYS group received significantly more neurostimulants (p < 0.001) and sleep medications (p = 0.02) compared with the NO-PHYS group. Analysis of covariance was conducted to examine FIM (motor and cognitive) changes from rehabilitation admission to discharge based on medications initiated in acute care. Those who received neither a neurostimulant nor a sleep medication had significantly lower FIM motor scores compared with those who received at least one of these medications (p = 0.047) and compared with those who received both types of medication (p = 0.17). No significant differences were found in FIM cognitive scores. The addition of a dedicated physiatrist providing early specialized care to patients who sustained a moderate or severe TBI was associated with improved functional outcomes upon discharge from rehabilitation. The presence of a dedicated trauma center physiatrist, trained in TBI rehabilitation, was also associated with a change in neuroprotective medication management in the acute care setting. Therapeutic study, level IV.


Bioavailability, disposition kinetics and dosage of sulfadimethoxine in dogs--a correction.
A reevaluation of the disposition kinetics and extent of absorption of sulfadimethoxine in normal dogs following intravenous and oral dosage has been made. The tissue to plasma level ratio at the peak tissue level (k12/k21) was 0.55, while the tissue to plasma level ratio after distribution equilibrium (k12/k21-beta) was 0.926. The systemic availability of sulfadimethoxine from the oral suspension was 48.8% (24.4-86.2) when corrections for intrasubject variability were made.


Combined use of dexmedetomidine and propofol in monitored anesthesia care: a randomized controlled study.
Although propofol and dexmedetomidine have been widely used for monitored anesthesia care, their adverse effects necessitate the search for better methods. Therefore, we performed this randomized controlled trial to evaluate the combined use of propofol and dexmedetomidine. Eighty-seven adult patients undergoing hand surgery under brachial plexus block were randomly allocated to receive 1.6 μg/ml of the target effect site concentration of propofol (P group) and infusion of 0.4 μg/kg/h dexmedetomidine following a loading dose of 1.0 μg/kg for 10 min (D group). The M group received a half-dose of both drugs simultaneously. The maintenance dose was adjusted to maintain an Observer Assessment of Alertness/Sedation score of 3. Cardiorespiratory variables, adverse effects, and drug efficacy were observed. The significantly higher mean arterial pressure (mmHg) in the D group [P group 86.9 (12.6), D group 96.0 (12.2), M group 85.6 (10.6), p = 0.004)] and a significantly higher heart rate (beat/min) in the P group were observed [P group 67.3 (9.0), D group 57.8 (6.9), M group 59.2 (7.4), p < 0.001)]. The M group had a significant lower incidence of airway obstruction (p < 0.001) and the D group had a higher incidence of bradycardia requiring atropine (p = 0.001). The P group had higher incidences of hypoxia (p = 0.001), spontaneous movement (p < 0.001) and agitation (p = 0.001). The satisfaction scores of the patients (p = 0.007) and surgeon (p < 0.001) were higher in the M group. Onset time was significantly longer in the D group (p < 0.001). The combined use of propofol and dexmedetomidine provided cardiovascular stability with decreased adverse effects. Additionally, it led to a similar onset time of propofol and achieved higher satisfaction scores. KCT0001284 . Retrospectively registered 25 November 2014.


Epidemiology and pattern of superficial fungal infections among primary school children in Enugu, south-east Nigeria.
Superficial fungal infections (SFIs) are prevalent among schoolchildren and result in significant morbidities that may lead to school absenteeism or school drop-out and hence setback in the education of the child. Differences exist in the epidemiology and pattern of SFIs among children in various geographical locations. Community-based studies on diseases are a true reflection of their pattern in that locality. There are no recent studies on this regard in south-east Nigeria despite the high prevalence reported in the country. This study aimed to determine the epidemiology and pattern of SFIs among children in rural and urban communities in Enugu, south-east Nigeria, for evidence-based effective interventions in this region. A comparative and descriptive cross-sectional study of primary school children from three randomly selected urban communities and three randomly selected rural communities was conducted. The sample size was determined with use of the formula for comparison of two proportions. A total of 1662 pupils were recruited through a multistage sampling method, with 831 from urban primary school populations and 831 from rural primary school populations. Data were analysed with IBM SPSS Statistics version 24. Of the 1662 children recruited, 748 had SFIs, with 502 (60.4%) seen in urban communities and 246 (29.6%) seen in rural communities. Tinea capitis was the most prevalent SFI (73.7%), and there was a statistically significant difference between urban (40.3%) and rural (26.1%) communities (P<0.001). The prevalence of SFIs was higher among urban female and rural male pupils. Children aged 9-12 years and 5-8 years were most commonly affected in the urban and rural communities, respectively. The personal hygiene of the children was poor in both communities. Emphasis on health education for SFIs and good personal hygiene will reduce the incidence of SFIs in the communities, especially among urban dwellers, which will encourage school attendance, concentration in class and child education.


An unusual dimeric structure of a Cu(I) bis(thiosemicarbazone) complex: implications for the mechanism of hypoxic selectivity of the Cu(II) derivatives.
The electrochemical reduction of Cu(II) bis(thiosemicarbazone) complexes [Cu(II)(btsc)] is accompanied by protonation to give an unstable Cu(I) intermediate [Cu(btscH(2))](+). The nature of this intermediate was probed by reaction of bis(thiosemicarbazone) ligands with a Cu(I) precursor which gave a novel helical dimeric dicationic complex. The dependence of these reactions on the ligand backbone substituents is discussed together with their possible relevance to the use of Cu(II) bis(thiosemicarbazone) ligands as hypoxic selective imaging and therapeutic agents.


Analysis of information processing stages using event-related potentials.
The event-related potential (ERP) was recorded to identify the time epochs during which different independent variables have their effects on stages in a memory search task. Stimulus intensity, memory set size and response type were varied. For the most part, the order and timing of effects (evaluated by Principal Components Analysis of within-subjects ERP differences) were consistent with the presumed underlying stages, except for early effects of response type prior to memory set effects (suggesting precategorical target recognition). The usefulness of this type of analysis for the investigation of information processing stages is discussed.


Alefacept: an expert review concerning the treatment of psoriasis.
Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy or immunosuppressive agents have been the first line of treatment for patients with severe psoriasis; however, the long-term use of these agents is limited by dose-dependent toxicities. Alefacept was the first biological agent approved in both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selectively reduces memory T cells. The efficacy and safety of up to two courses of alefacept have been demonstrated in clinical trials, and thus, this review focuses on new data to optimise the use of this biological agent. Emerging data indicates that multiple courses of alefacept for the long-term treatment of psoriasis are safe and effective. In addition, data are reviewed on the use of alefacept in combination with other agents and in other diseases, including psoriatic arthritis.


Occipital Nerve Blocks for Pediatric Posttraumatic Headache: A Case Series.
Posttraumatic headache is one of the most common and disabling symptoms after traumatic brain injury. However, evidence for treating posttraumatic headache is sparse, especially in the pediatric literature. This retrospective chart review evaluated the use of occipital nerve blocks in adolescents treated for posttraumatic headache following mild traumatic brain injury, presenting to the Complex Concussion and Traumatic Brain Injury clinic. Fifteen patients (mean age 15.47; range: 13-17) received occipital nerve block for posttraumatic headache. Follow-up was obtained in 14 patients at 5.57 (standard deviation = 3.52) months postinjury. The headache burden was high, with all except one having headaches 15 or more days per month (median 30, range 10-30). Sixty-four percent reported long-term response to the occipital nerve blocks, with associated improved quality of life and decreased postconcussion symptom scores (P < .05). One patient reported transient allopecia. Occipital nerve blocks are well tolerated and can be helpful in posttraumatic headache.


Mortality from esophageal cancer in Piedmont, Italy.
Piedmont is located at the borderline between Italy (where mortality from esophageal cancer is relatively low) and France and Switzerland (where it is relatively high). Therefore, it seemed of interest to investigate the mortality from this cancer in Piedmont. Age-adjusted yearly mortality rates for 1965-1969 were 4.3 and 0.8 per 100,000 for males and females, respectively. Rates were very similar in the town of Torino, in the 23 suburbs of the first belt, in the nonmetropolitan areas of the province of Torino, and in the other 5 provinces of Piedmont. In both sexes, the rates did not differ from those observed in Italy during 1966-1967, whereas rates for males were lower than the national rates for France and Switzerland (14.0 and 8.5/100,000/year, respectively). Rates for males were also lower than in the adjacent French departments of Savoie, Haute-Savoie, and Isère (where in 1967-1968 they ranged between 9 and 16). Mortality rates from esophageal cancer in the town of Torino were constant from 1951-1971. During the same period, mortality from laryngeal cancer in men doubled. This suggests that although some etiological agents (alcohol consumption and tobacco smoking) are common to esophageal and laryngeal cancer, the interplay between these 2 factors as well as that with other carcinogens is different for the 2 types of cancer.


The burden of asthma with specific reference to the United States.
During the second half of the 20th century, the increasing prevalence, morbidity, economic burden, and, in some countries, mortality from asthma have generated worldwide concern. The prevalence in the United States and other English-speaking countries is higher than that in most other countries, but worldwide variations cannot be explained by current knowledge of recognized risk or protective factors. According to hospital admission rates, asthma morbidity rates have also risen throughout the world during the past 40 years. These trends are likely due to many different factors, including an increase in the prevalence of severe asthma. Asthma mortality rates gradually declined in the United States during the 1960s and 1970s but have exhibited a substantial, progressive increase during the past 20 years. This trend stands in contrast to those in most other western countries, where asthma mortality rates have generally been decreasing during the 1990s. In both western and developing countries, the considerable economic burden of asthma disproportionately affects individuals with severe disease. This observation illustrates the potential for reducing the costs associated with asthma through management approaches that have been proven to reduce morbidity and mortality.


Antioxidant Bioactive Compounds Changes in Fruit of Quince Genotypes Over Cold Storage.
Quince fruit has many benefits to human health and is excellent source of bioactive compounds. The fruit of 15 quince genotypes stored at 2 °C for 5 mo to study fruit quality changes during cold storage. Fruit were sampled monthly and stored at 20 °C for 24 h. Fruit ascorbic acid (AA), total phenol (TP), and total flavonoid (TF) concentrations, total antioxidant activity (TAA), flesh browning (FB) incidence, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) activities were measured during storage. A high variation in bioactive compounds was observed across genotypes. The range of 26.8 to 44.4 mg/100 g FW for AA, 86.7% to 98.2% for TAA, 157.7 to 380.7 mg GAE 100(-1) g FW for TP, and 5.3 to 10.7 mg/100 g FW for TF were observed across genotypes at harvest time. The overall AA, TAA, TP, TF, and SOD decreased while PPO and POX increased during storage. FB was first observed after 4 mo and increased thereafter while the FB index was different across genotypes. Higher bioactive content may prevent or reduce FB index so that a negative correlation was found between FB and AA, TAA, TP, TF, and SOD.


Bis-corannulenoanthracene: An Angularly Fused Pentacene as a Precursor for Barrelene-Tethered Receptors for Fullerenes.
Bis-corannulenoanthracene (C50H22, 5) was prepared by the Diels-Alder double cycloaddition of isocorannulenofuran with "bis-benzyne", followed by deoxygenation of the adducts. Despite the presence of a pentacene core, 5 is stable enough to be isolated and stored. A cycloaddition reaction of 5 with maleic anhydride produces 10 which exhibits strong affinity toward C60, as evidenced by (1)H NMR titration experiment. Synthesis of 10 demonstrates the synthetic utility of hydrocarbon 5 in the preparation of the barrelene-based molecular clips with two benzocorannulene pincers adorned with polar substituents on their tethers, which will allow for immobilization of the receptors on solid supports.


Clinical importance of epicardial adipose tissue.
Different visceral fat compartments have several systemic effects and may play a role in the development of both insulin resistance and cardiovascular diseases. In the last couple of years special attention has been paid to the epicardial adipose tissue (EAT), which can be quantified by non-invasive cardiac imaging techniques. The epicardial fat is a unique fat compartment between the myocardium and the visceral pericardium sharing a common embryologic origin with the visceral fat depot. Epicardial adipose tissue has several specific roles, and its local effects on cardiac function are incorporated in the complex pathomechanism of coronary artery disease. Importantly, EAT may produce several adipocytokines and chemokines that may influence - through paracrine and vasocrine effects - the development and progression of coronary atherosclerosis. Epicardial adipose tissue volume has a relatively strong genetic dependence, similarly to other visceral fat depots. In this article, the anatomical and physiological as well as pathophysiological characteristics of the epicardial fat compartment are reviewed.


Development of a mobile groundwater desalination system for communities in rural India.
The consumption of saline groundwater has contributed to a growing incidence of renal diseases, particularly in coastal communities of India. Although reverse osmosis (RO) is routinely used to remove salt from groundwater, conventional RO systems (i.e. centralized systems using spiral wound RO elements) have limited utility in these communities due to high capital and maintenances costs, and lack of infrastructure to distribute the water. Consequently, there is a need to develop an appropriate solution for groundwater treatment based on small-scale, mobile and community-led systems. In this work, we designed a mobile desalination system to provide a simple platform for water treatment and delivery of goods to rural communities. The system employs tubular RO membranes packed in a single, low-profile vessel which fits below the cargo space. The low-profile enables minimal intrusion on the space available for the transportation of goods. Pressure is delivered by a belt driven clutch pump, powered by the engine. Water is treated locally by connecting the intake to the village well while the vehicle idles. A combined numerical and experimental approach was used to optimise the module/system design, resulting in ∼20% permeate flux enhancement. Experimental results revealed that the system can produce 16 L per square meter of membrane area per hour (LMH) at a salinity level of 80 ppm from a ∼2000 ppm groundwater when it is feed at 1 m3/h at 8 bars. This indicates that a vehicle equipped with 12 m2 of tubular RO membranes can deliver 1 m3 of drinkable water by using ∼0.9 L of diesel. Assuming eight such systems could be implemented in a community to fulfil the water demands for a village with 2000 residents, a social business study revealed that a payback time of 2.5 years is achievable, even if the sale price of the water is relatively low, USD 0.18 (Rs 12, which is half of the lowest market price) per 20 L, including providing a goods transportation service at price of USD 5.25 (Rs 350) per 100 km.


A model for analyzing competitive dynamics on triplex networks.
This paper studies the evolution process of competitive dynamics on triplex complex networks. We propose a new triplex network model in which the state of the node in each layer is affected by its neighbors as well as inter-layer competition. Through this model, we combine the opinion diffusion model, the Ising model, and the signed network and extend their application from single-layer to multi-layer networks. We derive the evolution process and dynamical equations of the model and carry out a series of numerical simulations to discuss the influence of several factors on the evolution process and the competitiveness of the network. First, we find that the increase of global transition threshold p or the proportion of initial active nodes will lead to more surviving layers and more active nodes in each layer. In addition, we summarize the similarities and differences of the evolution curves under different conditions. Second, we discuss the influence of initial active nodes and the average degree on the competitiveness of the network and find the correlations between them. Finally, we study the relationship between network topology and network competitiveness and conclude the conditions for the best competitiveness of the network. Based on the simulation results, we give specific suggestions on how to improve the competitiveness of the platform in reality.


Mechanism of immunopotentiation and safety of aluminum adjuvants.
Aluminum-containing adjuvants are widely used in preventive vaccines against infectious diseases and in preparations for allergy immunotherapy. The mechanism by which they enhance the immune response remains poorly understood. Aluminum adjuvants selectively stimulate a Th2 immune response upon injection of mice and a mixed response in human beings. They support activation of CD8 T cells, but these cells do not undergo terminal differentiation to cytotoxic T cells. Adsorption of antigens to aluminum adjuvants enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site which allows time for inflammatory cells to accumulate. The adsorptive strength is important as high affinity interactions interfere with the immune response. Adsorption can also affect the physical and chemical stability of antigens. Aluminum adjuvants activate dendritic cells via direct and indirect mechanisms. Phagocytosis of aluminum adjuvants followed by disruption of the phagolysosome activates NLRP3-inflammasomes resulting in the release of active IL-1β and IL-18. Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells. The use of aluminum adjuvant is limited by weak stimulation of cell-mediated immunity. This can be enhanced by addition of other immunomodulatory molecules. Adsorption of these molecules is determined by the same mechanisms that control adsorption of antigens and can affect the efficacy of such combination adjuvants. The widespread use of aluminum adjuvants can be attributed in part to the excellent safety record based on a 70-year history of use. They cause local inflammation at the injection site, but also reduce the severity of systemic and local reactions by binding biologically active molecules in vaccines.


Chronic exposure to 50Hz magnetic fields causes a significant weakening of antioxidant defence systems in aged rat brain.
Several studies suggest that extremely low-frequency magnetic fields (ELF-MFs) may enhance the free radical endogenous production. It is also well known that one of the unavoidable consequences of ageing is an overall oxidative stress-based decline in several physiological functions and in the general resistance to stressors. On the basis of these assumptions, the aim of this study was to establish whether the ageing process can increase susceptibility towards widely present ELF-MF-mediated pro-oxidative challenges. To this end, female Sprague-Dawley rats were continuously exposed to a sinusoidal 50 Hz, 0.1 mT magnetic field for 10 days. Treatment-induced changes in the major antioxidant protection systems and in the neurotrophic support were investigated, as a function of the age of the subjects. All analyses were performed in brain cortices, due to the high susceptibility of neuronal cells to oxidative injury. Our results indicated that ELF-MF exposure significantly affects anti-oxidative capability, both in young and aged animals, although in opposite ways. Indeed, exposed young individuals enhanced their neurotrophic signalling and anti-oxidative enzymatic defence against a possible ELF-MF-mediated increase in oxygen radical species. In contrast, aged subjects were not capable of increasing their defences in response to ELF-MF treatment but, on the contrary, they underwent a significant decrease in the major antioxidant enzymatic activities. In conclusion, our data seem to suggest that the exposure to ELF-MFs may act as a risk factor for the occurrence of oxidative stress-based nervous system pathologies associated with ageing.


Evidence for developing fractional quantum Hall states at even denominator 1/2 and 1/4 fillings in asymmetric wide quantum wells.
We report the observation of developing fractional quantum Hall states at Landau level filling factors nu = 1/2 and 1/4 in electron systems confined to wide GaAs quantum wells with significantly asymmetric charge distributions. The very large electric subband separation and the highly asymmetric charge distribution at which we observe these quantum Hall states, together with the fact that they disappear when the charge distribution is made symmetric, suggest that these are one-component states, possibly described by the Moore-Read Pfaffian wave function.


[Insulin-dependent diabetes associated with celisc disease in two families].
Two families in which insulin-dependent diabetes was associated with coeliac disease were studied. All patients had the HLA B 8 antigens. In one case there was an association of HLA B 8 with BW 15. The HLA B 8 determinant was found in that of the parents with a familial diabetic trait. These findings contribute to replace the association diabetes-coeliac disease in the larger frame of auto-immune diseases.


Impact of low-level fine particulate matter and ozone exposure on absences in K-12 students and economic consequences.
High air pollution levels are associated with school absences. However, low level pollution impacts on individual school absences are under-studied. Understanding the variability of pollution at individual schools within an urban region could improve school recess decisions, better identify local pollution sources, and improve local economic impact assessments by providing granular information relevant to specific schools. We modelled PM2.5 and ozone concentrations at 36 schools from July 2015 to June 2018 using data from a dense, research grade regulatory sensor network. We determined exposures and daily absences at each school. We used a generalized estimating equations model to retrospectively estimate rate ratios for association between outdoor pollutant concentrations and school absences. We estimated lost school revenue, productivity, and family economic burden. PM2.5 and ozone concentrations and absence rates vary across the School District. Pollution exposure was associated with a rate ratio as high as 1.02 absences per μg m-3 and 1.01 per ppb increase for PM2.5 and ozone, respectively. Significantly, even PM2.5 and ozone exposure below the air quality index breakpoints for good air quality (<12.1 μg m-3 and <55 ppb, respectively) was associated with positive rate ratios of absences: 1.04 per μg m-3 and 1.01 per ppb increase, respectively. Granular local measurements enabled demonstration of air pollution impacts that varied between schools and were undetectable with averaged pollution levels. Reducing pollution by 50% would save $426000 per year districtwide. Pollution reduction benefits would be greatest in schools located in socioeconomically disadvantaged areas. Heterogeneity in exposure, disproportionately affecting socioeconomically disadvantaged schools, points to the need for fine resolution exposure estimation. The economic cost of absences associated with air pollution is substantial even excluding indirect costs such as hospital visits and medication. These findings may help elucidate the differential burden on individual schools and inform local decisions about recess and regulatory considerations for localized pollution sources.


Mullerian adenosarcoma of the uterine cervix.
Sarcomas in the uterine cervix are rare, the incidence being 0.5% to 1% of all cervical malignancies. This is a report of cervical mullerian adenosarcoma, which was encountered in a hysterectomy performed for prolapse. The tumor was composed of benign glandular elements and malignant stromal component, thus justifying its nomenclature. We wish to emphasize the distinctive morphological features of this rare cervical tumor.


Helminths of freshwater animals from five provinces in northern Thailand.
Seven species of fishes, 6 species of mollusks, 1 species of crab, and 1 species of shrimp were collected from 12 natural freshwater sites from 5 provinces: Lumpang, Phrae, Phayao, Chiang Rai and Chiang Mai during the Rainy season of 2000. Fishes, Channa striatus, Dermogenus pusillus, Oxyeleotris marmoratus, Trichogaster trichopterus and Trichopsis vittatus were examined for helminths and 34.69% (17/49) were infected. There were 2 genera of monogenean identified as follows: Dactylogyrus and Trianchoratus; 3 genera of metacercariae were as follows: Acanthostomum, Posthodiplostomum and Stellantchasmus. Furthermore, 1 genus of Acanthocephala was found from fishes to be Pallisentis sp. The prevalence of infection in mollusks was 6.20% (17/274); Pleurolophocercous and Furcocercous cercariae were observed only in one species of mollusks, Melanoides sp. A crab and a shrimp were negative.


Characterization of local delivery with amphotericin B and vancomycin from modified chitosan sponges and functional biofilm prevention evaluation.
Polymicrobial musculoskeletal wound infections are troublesome complications and can be difficult to treat when caused by invasive fungi or bacteria. However, few local antifungal delivery systems have been studied. Chitosan and polyethylene glycol (PEG) sponge local antifungal delivery systems have been developed for adjunctive therapy to reduce musculoskeletal wound contamination. This study evaluated the effects of blending PEG, at 6,000 or 8,000 g/mol, with chitosan in sponge form on in vitro amphotericin B and vancomycin elution, eluate activity, cytocompatibility, and in vivo prevention of a bacterial biofilm. Blended chitosan sponges released both amphotericin B and vancomycin in vitro. All tested amphotericin B eluates remained active against Candida albicans, and vancomycin eluates from blended sponges maintained activity against Staphylococcus aureus. Amphotericin B eluates obtained after 1 h from blended sponges elicited 62-95% losses in fibroblast viability, but 3 h eluates only caused 22-60% decreases in viability. In a Staphylococcus aureus infected mouse catheter biofilm prevention model, vancomycin loaded chitosan/PEG 6000 sponge cleared bacteria from 100% of the catheters, with reduced clearance rate observed in other sponges. These results indicate that the chitosan/PEG blended sponges have potential for local antifungal and/or antibiotic combination delivery as an adjunctive therapy to prevent wound infections.


Return to Play After Forearm and Hand Injuries in the National Basketball Association.
Hand injuries can result in significant time away from competition for professional basketball players. Time to return to play after hand injuries in elite athletes has not been well described. To report the return to play from metacarpal fractures, phalangeal fractures, and thumb ligament tears in National Basketball Association (NBA) players over a 5-year period. Descriptive epidemiology study. The NBA transaction report was analyzed from January 2009 to May 2014. Players were identified if they were added to the inactive list (IL), missed games due to their injury, or underwent surgery as a result of hand injury. Number of games missed due to injury, days spent on the IL, and age at injury were calculated by injury type and location. One hundred thirty-seven injuries were identified: 39 injuries to the hand and 98 injuries to the finger. Three major injury patterns were identified and analyzed: metacarpal fractures (n = 26), phalangeal fractures (n = 33), and thumb ligament tears (n = 9). The type of injury sustained affected return to play (P < .05). All thumb ligament tears required surgery and had the longest return to play of 67.5 ± 17.7 days (P < .05). The return to play for surgically treated metacarpal fractures (56.7 ± 26.3 days) was significantly greater than nonsurgically treated metacarpal fractures (26.3 ± 12.1 days; P < .01). Return to play for surgically repaired phalangeal fractures (46.2 ± 10.8 days) trended greater but was not significantly different than phalangeal fractures treated nonsurgically (33.3 ± 28.5 days; P = .21). Hand injuries in professional basketball players can lead to prolonged periods of time away from competition, especially after surgery. This study provides guidelines on expected return to play in the NBA after these common hand injuries.


Mid-term results of mitral valve repair with autologous pericardium in pediatric patients.
Mitral valve repair to treat mitral regurgitation (MR) in pediatric patients remains challenging because of the complex morphology and fragility of the leaflets. The study aim was to review retrospectively the authors' experience with mitral valve repair using autologous pericardium. Between April 2004 and November 2011, nine pediatric patients (six males, three females; mean age 2.4 +/- 4.5 years) underwent mitral valve repair with an autologous fresh (n = 5) or glutaraldehyde-treated pericardium (n = 4) to treat severe MR. The etiology of the MR was acute endocarditis, acute chordal rupture and congenital disease in three, two, and four patients, respectively. Autologous pericardium was used for valvuloplasty, leaflet extension plasty and commissuroplasty in two, five, and two patients, respectively. Artificial chordal replacement was performed in three patients. No operative deaths or postoperative endocarditis occurred. One patient required mitral valve replacement at three days after the initial mitral repair. The most recent echocardiography findings of the remaining patients after a mean of 6.3 years (range: 1.3-9.0 years) showed that the severity of mitral insufficiency, left ventricular diastolic diameter and fractional shortening were 1.8 +/- 0.6 (grades 0-4), 40.4 +/- 8.4 mm (114.2 +/- 15.8% of normal) and 35.0 +/- 5.0%, respectively. Mitral valve repair using autologous fresh pericardium is associated with mid-term durability and resistance to infection when used for mitral valve repair of active endocarditis in pediatric patients. Augmentation with autologous pericardium could become an alternative to current surgical options.