Three-dimensional time-of-flight MR angiography in the evaluation of intracranial aneurysms treated with Guglielmi detachable coils.
Intravascular treatment of intracranial aneurysms is a relatively new therapeutic technique and long-term controlled angiographic trials are needed to assess persistence of aneurysm occlusion. Our purpose was to evaluate the effectiveness of 3D time-of-flight (3D-TOF) MR angiography as a noninvasive screening tool in the follow-up of cerebral aneurysms treated with Guglielmi detachable coils (GDCs). Forty-nine patients with 50 intracranial aneurysms previously treated with GDCs were studied with both DSA and 3D-TOF MR angiography. In 14 cases, a second follow-up examination was performed, for a total of 64 aneurysms evaluated. In 25 aneurysms, both pre- and postcontrast MR angiographic studies were obtained. In seven of 64 aneurysms, the MR angiographic studies were considered to be unreliable owing to the presence of artifacts that obscured part of the parent artery and did not allow an accurate evaluation of the aneurysm neck. These seven aneurysms, however, all were shown to be completely occluded at digital subtraction angiography (DSA). In the remaining 57 aneurysms, DSA revealed complete occlusion in 39 and the presence of residual patency in 18, whereas MR angiography showed complete occlusion in 38 and residual patency in 19. Enhanced MR angiography proved to be useful in evaluating residual patency in large and giant aneurysms and in better depicting the distal branch arteries. Although artifacts related to the presence of coils are evident on a considerable number of imaging studies, our findings indicate that MR angiography is useful in the evaluation of residual patency of cerebral aneurysms treated with GDCs and may eventually prove valuable in the follow-up of those cases in which a good initial correlation with DSA was demonstrated.


Virus and host interactions critical for filoviral RNA synthesis as therapeutic targets.
Filoviruses, which include Ebola virus (EBOV) and Marburg virus, are negative-sense RNA viruses associated with sporadic outbreaks of severe viral hemorrhagic fever characterized by uncontrolled virus replication. The extreme virulence and emerging nature of these zoonotic pathogens make them a significant threat to human health. Replication of the filovirus genome and production of viral RNAs require the function of a complex of four viral proteins, the nucleoprotein (NP), viral protein 35 (VP35), viral protein 30 (VP30) and large protein (L). The latter performs the enzymatic activities required for production of viral RNAs and capping of viral mRNAs. Although it has been recognized that interactions between the virus-encoded components of the EBOV RNA polymerase complex are required for viral RNA synthesis reactions, specific molecular details have, until recently, been lacking. New efforts have combined structural biology and molecular virology to reveal in great detail the molecular basis for critical protein-protein interactions (PPIs) necessary for viral RNA synthesis. These efforts include recent studies that have identified a range of interacting host factors and in some instances demonstrated unique mechanisms by which they act. For a select number of these interactions, combined use of mutagenesis, over-expressing of peptides corresponding to PPI interfaces and identification of small molecules that disrupt PPIs have demonstrated the functional significance of virus-virus and virus-host PPIs and suggest several as potential targets for therapeutic intervention.


Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.
Records of 73 patients with medullary thyroid cancer were reviewed to assess prognostic factors and the role of external beam radiation therapy. Patients were treated between 1954 and 1992. The median age was 49 years (range 15-85), M:F ratio 1.6:1, and the median follow-up was 7.9 years. (2.5-34.6). The primary tumor size was < 1 cm in 10%, 1-4 cm in 53%, and > 4 cm in 37%. Multifocality was noted in 32%, and 23% had metastasis at presentation. Eight patients presented with inoperable tumors, 40% had gross, and 37% microscopic residual disease postthyroidectomy. Extraglandular extension was present in 56%, and 74% had pathologically involved lymph nodes. Treatment was by total or near total thyroidectomy in 41 patients; 37 had a lymph node dissection. Forty-six patients were irradiated, the dose of radiation ranging from 20 to 75.5 Gy; median was 40 Gy, treatment time median was 28 days and the median number of fractions was 20. The overall cause specific survival (CSS) was 70% and 57% at 5 and 10 years, respectively. In a univariate analysis, the following factors predicted for lower CSS: age as a continuous variable (p = 0.003), male gender (p = 0.008), presence of distant metastasis (p < 0.0001), lymph node involvement (p = 0.03), gross residual disease (p < 0.0001), tumor size > 4 cm (p = 0.05), extraglandular invasion (p < 0.004), vascular invasion (p = 0.007), diarrhea (p < .0007), and abnormal postoperative calcitonin (p = 0.02). On multivariate analysis only two factors were significant: the presence of extraglandular invasion, and postoperative gross residual disease. There was no difference in local/regional relapse free rate between patients receiving external radiation and those that did not, but in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse.


Optical particle manipulation using an LC device with eight-divided circularly hole-patterned electrodes.
We propose an optical manipulation system by using a liquid crystal (LC) device with unique functions such as an anamorphic lens property, variable-focusing and deflection properties. The positions and rotation of optical trapped microscopic slender particles suspended in water can be controlled. The trapped particles can be aligned along the major axis of the elliptically shaped laser beam spot and the position of the particle can be controlled three-dimensionally.


Comparison of Vision-related Quality of Life Between Normal Tension Glaucoma and Primary Open-angle Glaucoma.
Although there was little difference in overall vision-related quality of life (VRQOL) between patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) after controlling for confounding factors, POAG tended to have poorer VRQOL, especially in social functioning and dependency, than NTG. The fundamental goal of treatment of patients with glaucoma is to preserve their VRQOL. The aim of this study was to compare VRQOL between patients with NTG and those with POAG. The self-reported National Eye Institute Visual Function Questionnaire (NEI VFQ-25) survey was performed, including clinical, demographic, and socioeconomic data from 506 Korean patients with NTG and 287 with POAG. The mean deviation of the integrated binocular visual field was calculated using the best location method. The NEI VFQ-25 results were evaluated by Rasch analysis to control item difficulty and variation in individual response ability. Propensity score matching was used to control for various confounding factors affecting VRQOL. Although patients with POAG tended to have worse VRQOL than those with NTG, there was no statistically significant between-group difference in ocular pain, near and distance activities, mental health, role difficulties, ability to drive, and the overall composite score. However, the social functioning (P=0.016) and dependency (P=0.026) were significantly poorer in POAG patients. Overall VRQOL in patients with NTG and POAG was found to be similar. However, social functioning and dependency were significantly worse in those with POAG. These findings are relevant to supporting glaucoma patients.


A conserved role for Hox paralog group 4 in regulation of hematopoietic progenitors.
Regulatory circuits that control stem cell fate decisions can be identified and understood by manipulating individual regulatory elements genetically. While impractical in the rare somatic stem cells of primary tissue, this approach is feasible in embryonic stem cells differentiated in vitro into the somatic stem cell type of interest. We present an improved highly efficient targeting system allowing genes to be integrated into a predetermined, doxycycline-inducible locus, and corresponding inducible embryonic stem cell lines to be generated rapidly. We apply this system to evaluate a key hematopoietic progenitor cell regulatory element, HoxB4, and its mammalian paralogs, whose effects have not yet been tested in this context. We show that all Hox paralog group 4 members, A4, B4, C4, and D4, have similar effects on hematopoietic stem and progenitor self-renewal in vitro, and thus classify Hox paralog group 4 as promoting self-renewal. Each paralog group 4 member both promotes proliferation and inhibits differentiation, enabling the exponential expansion of hematopoietic progenitors from the c-kit(+)/CD41(+) cell fraction of day 6 murine embryoid bodies. By evaluating a set of deletion mutants we show that sequences in addition to the homeodomain and hexapeptide motif are required for this activity. These results highlight the utility of this expression system to perform functional and structural analyses of genetic regulators of cell fate decisions.


MDCT-QCT, QUS, and DXA in healthy adults: An intermodality comparison.
Background: Cortical deceleration is the main reason for bone loss at peripheral sites. It was suggested that when peripheral bones were assessed for osteoporosis, management and therapy can be administered early. The main aim of this study was to assess the relationships between the central and peripheral measurements at different skeleton bone sites (spine, femur, forearm, tibia, and calcaneus) with available modalities: DXA, QUS, and MDCT-QCT. Methods: The volunteers recruited in this study did not have any history or evidence of metabolic bone disease. Blood test and DXA measurements were used as inclusion criteria to select 40 healthy participants. The selected volunteers underwent 3 imaging modalities: QCT, DXA, and QUS. DXA-based measurements were made on 3 sites, including spine, femur, and forearm. QCT and QUS measurements were done for distal of tibia and calcaneus bones, respectively. The extracted parameters from the 3 modalities were analyzed using a bivariate (Pearson) correlation (r) in statistical software. Results: The results showed moderate to good correlations between spongy bones in central and peripheral sites from all the modalities. However, there was no correlation between MDCT measures and central bone values. According to correlations between different peripheral sits, aBMD of 33% radius and trabecular vBMD in 38% distal tibia showed weak but significant relationship between peripheral bones (r=-0.342, p=0.044). Conclusion: The findings demonstrated how bones in central and peripheral sites were correlated. Multimodality imaging was used in this group of healthy volunteers. Also, it was found that QCT-based MDCT needs more optimization and requires further investigations.


A highly sensitive method for analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz syndrome.
We describe a highly sensitive method for the detection of 7-dehydrocholesterol (7-DHC), the biosynthetic precursor of cholesterol, based on its reactivity with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in a Diels-Alder cycloaddition reaction. Samples of biological tissues and fluids with added deuterium-labeled internal standards were derivatized with PTAD and analyzed by LC-MS. This protocol permits fast processing of samples, short chromatography times, and high sensitivity. We applied this method to the analysis of cells, blood, and tissues from several sources, including human plasma. Another innovative aspect of this study is that it provides a reliable and highly reproducible measurement of 7-DHC in 7-dehydrocholesterol reductase (Dhcr7)-HET mouse (a model for Smith-Lemli-Opitz syndrome) samples, showing regional differences in the brain tissue. We found that the levels of 7-DHC are consistently higher in Dhcr7-HET mice than in controls, with the spinal cord and peripheral nerve showing the biggest differences. In addition to 7-DHC, sensitive analysis of desmosterol in tissues and blood was also accomplished with this PTAD method by assaying adducts formed from the PTAD "ene" reaction. The method reported here may provide a highly sensitive and high throughput way to identify at-risk populations having errors in cholesterol biosynthesis.


Detecting cell death with optical coherence tomography and envelope statistics.
Currently no standard clinical or preclinical noninvasive method exists to monitor cell death based on morphological changes at the cellular level. In our past work we have demonstrated that quantitative high frequency ultrasound imaging can detect cell death in vitro and in vivo. In this study we apply quantitative methods previously used with high frequency ultrasound to optical coherence tomography (OCT) to detect cell death. The ultimate goal of this work is to use these methods for optically-based clinical and preclinical cancer treatment monitoring. Optical coherence tomography data were acquired from acute myeloid leukemia cells undergoing three modes of cell death. Significant increases in integrated backscatter were observed for cells undergoing apoptosis and mitotic arrest, while necrotic cells induced a decrease. These changes appear to be linked to structural changes observed in histology obtained from the cell samples. Signal envelope statistics were analyzed from fittings of the generalized gamma distribution to histograms of envelope intensities. The parameters from this distribution demonstrated sensitivities to morphological changes in the cell samples. These results indicate that OCT integrated backscatter and first order envelope statistics can be used to detect and potentially differentiate between modes of cell death in vitro.


Indocyanine green-mediated antimicrobial photodynamic therapy as an adjunct to periodontal therapy: a systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to evaluate the efficacy of indocyanine green-mediated photodynamic therapy (ICG-PDT) as an adjunct to non-surgical periodontal therapy (NSPT), in the management of chronic periodontitis. Four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Embase via OVID, Web of Science) were searched for randomised controlled trials comparing NSPT with ICG-PDT to NSPT without laser therapy. Primary outcome measures were changes in probing pocket depth (PPD) and clinical attachment level (CAL). Clinical outcomes were extracted and pooled from 7 eligible trials and meta-analyses conducted using mean difference with standard deviations. For PPD, adjunctive ICG-PDT resulted in a mean additional reduction of 1.17 mm (95% CI: 0.67-1.66 mm) at 3 months and a mean additional reduction of 1.06 mm (95% CI: 0.54-1.57 mm) at 6 months. For CAL, adjunctive ICG-PDT resulted in a mean additional gain of 0.70 mm (95% CI: 0.17-1.23 mm) at 3 months and a mean additional gain of 1.03 mm (95% CI: 0.83-1.24 mm) at 6 months. No adverse events were reported in any studies. The adjunctive use of ICG-PDT in NSPT results in improved treatment outcomes at 3 and 6 months post-therapy. Further investigation is needed to evaluate variables such as different photosensitiser concentrations and adjusting parameters associated with the light source. Indocyanine green-based photosensitisers may be a novel, clinically efficacious agent for use in the management of periodontitis.


Cardiorespiratory fitness and cardiovascular disease - The past, present, and future.
The importance of cardiorespiratory fitness (CRF) is now well established and it is increasingly being recognized as an essential variable which should be assessed in health screenings. The key findings that have established the clinical significance of CRF are reviewed in this report, along with an overview of the current relevance of exercise as a form of medicine that can provide a number of positive health outcomes, including increasing CRF. Current assessment options for assessing CRF are also reviewed, including the direct measurement via cardiopulmonary exercise testing which now can be interpreted with age and sex-specific reference values. Future directions for the use of CRF and related measures are presented.


[Neckpain: additional investigations only when there is an indication--treatment is rarely necessary].
In this article, we describe the case of a 44-year-old secretary who developed neck pain. Without first having consulted her general practitioner, she visited a chiropractor who concluded that she had 'irritation of the nerves', which the patient interpreted as a herniation of a cervical disc. She believed an MRI to be necessary. She underwent a total body scan at a commercial facility which revealed degenerative changes of the cervical and lumbar spine and an arachnoid cyst in the brain. We could not reassure this patient; however, unnecessary investigations and treatment in a different patient could be prevented. Additional investigations for neck pain without neurological signs on examination are only necessary for a few patients. Chiropractic may have serious side effects. Confusing information about neck pain appearing on the Internet and in medical journals should be contested with information based on the solid, critical appraisal of studies.


The impact of body mass index and type 2 diabetes on breast cancer: current therapeutic measures of prevention.
Epidemiological data have suggested a possible relationship between obesity, diabetes mellitus and cancer risk, particularly breast cancer. We set out to investigate the effect of body mass index and diabetes mellitus on the presence of breast cancer in the Apulian population. We selected 1,663 women affected with primary breast cancer and 4,702 control patients. All patients with breast cancer underwent surgical excision of the tumor and their tumors were histologically confirmed. The prevalence of type 2 diabetes (8%) in the women affected by breast cancer was significantly higher than in the control group (5%) (p<0.05). The majority of the diabetic women affected by breast cancer had a BMI value >25, both in premenopause and in postmenopause. With respect to BMI, the non-diabetic patients with breast cancer in postmenopause showed the same pattern as the diabetic ones. Instead, among the women in premenopause a higher percentage (55%) of patients with a BMI <24.9 was found (p<0.01). In the Apulian population, the presence of both type 2 diabetes and elevated values of BMI (that is in a condition of hyperinsulinemia) were found to enhance the frequency of breast cancer.


Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion-An Omics Network Approach.
The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins' glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.


Leontio Lyceum ALbuminuria (3L Study) epidemiological study: aims, design and preliminary findings.
The significance of microalbuminuria (MA) in paediatric essential hypertension has yet to be established. The Leontio Lyceum ALbuminuria Study (3L Study) was designed to determine the prevalence of MA among Greek schoolchildren and to evaluate these rates in relation to the children's anthropometric and lifestyle characteristics, and dietary habits. During April 2009, 498 students from the Leontio Lyceum, aged 12-17 years (7th-12th grade), were asked to participate in the 3L Study. For each child a questionnaire was completed that was developed for the purposes of the study to retrieve information on socio-demographic and lifestyle characteristics, as well as dietary habits (through a semi-quantitative Food Frequency Questionnaire), and physical activity status. Overweight and obesity were defined using the international body mass index cut-off points established for children and young people. Office blood pressure (BP) was measured on two different occasions and those students who had BP >95th percentile for gender, age and height on both occasions were considered as hypertensives. Microalbuminuria was determined as albumin to creatinine ratio >or=22 mg/g in boys and >or=31 mg/g in girls in a morning spot urine sample using a quantitative assay (DCA 2000). The prevalence of MA was found to be 12.9% and that of childhood hypertension 5.2%. The prevalence of overweight status was 25.8% and 5.8% of the students were classified as obese. Low physical activity was reported by 7% of boys and girls, while 46.5% of the students reported participation in vigorous physical activities during a normal week. Based on the KIDMED score of each student, only 6% of them were classified as high adherers to a Mediterranean diet and 41.9% were classified as having very low diet quality. In this paper we present the aims, design and preliminary results of an epidemiological study on MA, hypertension, increased body size and lifestyle characteristics among Greek schoolchildren.


Antibiotic elution from bone cement: A study of common cement-antibiotic combinations.
The in vitro antibiotic elution characteristics (including the effects of cement fracture) of the following cements were studied: 1) CMW 1 with gentamicin, 2) Palacos R with gentamicin, 3) Palacos LV with gentamicin, 4) CMW 1 with gentamicin and vancomycin, 5) Palacos R with gentamicin and vancomycin, 6) CMW 1 with gentamicin and flucloxacillin, and 7) Palacos R with gentamicin and flucloxacillin. Elution of both gentamicin and vancomycin was satisfactory in all cases. There tended to be a peak of antibiotic release on cement fracture, suggesting sequestration of active antibiotic within deeper layers of the cement. Palacos LV exhibited the best antibiotic elution characteristics but with the highest post-fracture peak. Palacos R was superior to CMW 1. Flucloxacillin was present only until day 4. Adulteration of proprietary Palacos R/gentamicin with flucloxacillin produced prolonged high elution of gentamicin, possibly due to porosity. Flucloxacilloic acid (microbiologically inactive) was present from day 4 onwards after flucloxacillin was added to cement. These findings suggest that flucloxacillin is not a suitable additive to bone cement in revision surgery. (Hip International 2002; 1: 23-7).


[Juvenile low back pain: clinical approach in 2010].
The first part of this article reviews the evolution of diagnostic issues regarding low back pain (LBP) in children and adolescents in recent years. The attitude recommended in the literature has been adapted to current epidemiological data showing that non specific LBP is largely prevalent in these age groups, much like in adult populations. Thus, it seems reasonable to avoid an overly aggressive therapeutic attitude, especially in the adolescent population. The second part of the article is devoted to non specific LBP and summarizes recent studies. These data show that the impact of LBP on the quality of life in children and adolescents is very low, with the exception, however, of a small subgroup of adolescents suffering generalized pain in conjunction with LBP.


Systemic treatment of advanced thymic malignancies.
The rarity of thymic malignancies prevents us from performing large randomized clinical trials. As a result, systemic treatment decisions are often guided by a small amount of prospective trial data, retrospective series, and individual case reports. In recent years, we have begun to unravel the molecular biology of thymic tumors. It is becoming more apparent as a result of gene expression profiling and genomic clustering studies that the subclassifications of type A, AB, B1, B2, B3, and thymic carcinoma have different molecular features that may be clinically relevant. Genomic profiling distinguishes type B3 thymoma and thymic carcinoma as distinct entities from type A and type B2 thymoma. Furthermore, type B2 thymomas can be separated from other subgroups in that it has a more distinct lymphocytic component than the other groups where epithelial cells predominate. Next generation RNA sequencing has recently identified a large microRNA cluster on chromosome 19q13.42 in types A and AB thymomas, which is absent in type B thymomas and thymic carcinomas. This cluster has been shown to result in activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which suggests a possible role for PI3K inhibitors in these subtypes. The presence of KIT mutations in thymic carcinomas is also well described. Herein we discuss the chemotherapeutic and targeted treatment options for advanced thymic malignancies and highlight important advances in our understanding of the molecular biology of these rare tumors.


The c-MYC-ABCB5 axis plays a pivotal role in 5-fluorouracil resistance in human colon cancer cells.
c-MYC overexpression is frequently observed in various cancers including colon cancer and regulates many biological activities such as aberrant cell proliferation, apoptosis, genomic instability, immortalization and drug resistance. However, the mechanism by which c-MYC confers drug resistance remains to be fully elucidated. In this study, we found that the c-MYC expression level in primary colorectal cancer tissues correlated with the recurrence rate following 5-fluorouracil (5-FU)-based adjuvant chemotherapy. Supporting this finding, overexpression of exogenous c-MYC increased the survival rate following 5-FU treatment in human colon cancer cells, and knockdown of endogenous c-MYC decreased it. Furthermore, c-MYC knockdown decreased the expression level of ABCB5, which is involved in 5-FU resistance. Using a chromatin immunoprecipitation assay, we found that c-MYC bound to the ABCB5 promoter region. c-MYC inhibitor (10058-F4) treatment inhibited c-MYC binding to the ABCB5 promoter, leading to a decrease in ABCB5 expression level. ABCB5 knockdown decreased the survival rate following 5-FU treatment as expected, and the ABCB5 expression level was increased in 5-FU-resistant human colon cancer cells. Finally, using a human colon cancer xenograft murine model, we found that the combined 5-FU and 10058-F4 treatment significantly decreased tumorigenicity in nude mice compared with 5-FU or 10058-F4 treatment alone. 10058-F4 treatment decreased the ABCB5 expression level in the presence or absence of 5-FU. In contrast, 5-FU treatment alone increased the ABCB5 expression level. Taken together, these results suggest that c-MYC confers resistance to 5-FU through regulating ABCB5 expression in human colon cancer cells.


Statins have therapeutic potential for the treatment of Alzheimer's disease, likely via protection of the neurovascular unit in the AD brain.
Structural and functional abnormalities in the neurovascular unit (NVU) have been recently observed in Alzheimer's disease (AD). Statins, which are used clinically for reducing cholesterol levels, can also exert beneficial vascular actions, improve behavioral memory and reduce senile plaque (SP). Thus, we examined cognitive function, the serum level of lipids, senile plaque (SP), and the protective effects of statins on NVU disturbances in a mouse AD model. Amyloid precursor protein (APP) transgenic (Tg) mice were used as a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3mg/kg/day, p.o.) were administered from 5 to 20 months of age. These 2 statins improved behavioral memory and reduced the numbers of SP at 15 and 20 M without affecting serum lipid levels. There was a reduction in immunopositive staining for N-acetyl glucosamine oligomer (NAGO) in the endothelium and in collagen IV in the APP vehicle (APP/Ve) group, with collagen IV staining most weakest near SP. There was also an increase in intensity and numbers of glial fibrillary acidic protein (GFAP) positive astrocytes, particularly around the SP, where MMP-9 was more strongly labeled. Double immunofluorescent analysis showed that astrocytic endfeet had detached from the capillary endothelium in the APP/Ve group. Overall, these data suggest that statins may have therapeutic potential for AD by protecting NVU.


Chronic administration of recombinant ovine leptin in growing beef heifers: effects on secretion of LH, metabolic hormones, and timing of puberty.
Serum concentrations of leptin increase linearly from approximately 16 wk before until the week of pubertal ovulation in beef heifers. To test the hypothesis that exogenous leptin can hasten the onset of puberty in heifers, we examined the effects of chronic administration of recombinant ovine leptin (oleptin) on timing of puberty, pulsatile and GnRH-mediated release of LH, and plasma concentrations of GH, IGF-I, and insulin. Fourteen fall-born, prepubertal heifers (Brahman x Hereford, 12 to 13 mo; 304.7+/-4.12 kg) were used. Heifers were stratified by age and BW and assigned randomly to one of two groups (seven animals per group): 1) Control; heifers received s.c. injections of saline twice daily (0700 and 1900) for 40 d; and 2) Leptin; heifers received s.c. injections of oleptin (19.2 microg/kg) twice daily at 0700 and 1900 for 40 d. Blood samples were collected at 10-min intervals for 5 h on. d 0, 5, 10, 20, 30, and 40, and twice daily, just before each treatment injection, throughout the study. On d 41, heifers received i.v. injections of GnRH at 0 (0.0011 microg/kg) and 90 min (0.22 microg/kg), with additional sampling for 5.5 h to examine releasable pools of LH. Diets promoted a gain of 0.32+/-0.09 kg/d, which did not differ between groups. Plasma concentrations of leptin increased markedly in leptin-treated heifers and were greater (P < 0.001) than controls throughout (27.8+/-0.8 vs. 4.9+/-0.12 ng/mL). None of the heifers reached puberty during the experiment, but did so within 45 d of its termination. Mean concentrations of plasma LH, GH, IGF-I, and insulin were not affected by treatment, nor was there an overall effect on the frequency of LH pulses. However, a treatment x day interaction (P = 0.02) revealed that the frequency of LH pulses (pulses/ 5 h) was greater (P = 0.03) in controls (3.6+/-0.36) than in leptin-treated heifers (1.7+/- 0.28) on d 10. Characteristics of GnRH-induced release of LH were not affected by treatment. In summary, chronically administered leptin failed to induce puberty or alter endocrine characteristics in beef heifers nearing the time of expected puberty.


Active targeting strategies for anticancer drug nanocarriers.
Chemotherapy at present remains the main form of treatment for cancer, though there is no clinically available antineoplastic drug that acts selectively on the tumor mass. For this reason, the scientific research is focused towards the development of novel cancer therapies and drug delivery strategies, like drug targeting, that would enhance the therapeutic efficacy of drugs while reducing their side toxicity. This review describes tree types of nanoparticles used in active targeting for cancer treatment: liposomes, lipid and polymer nanoparticles, and micelles. The opportunities and challenges achieved by the proposed strategies of active targeting have been highlighted, as well as the necessity to conciliate the targeting efficiency of drug nanocarriers with their longevity in the bloodstream.


Genome sequencing and identification of cellulase genes in Bacillus paralicheniformis strains from the Red Sea.
Cellulolytic microorganisms are considered a key player in the degradation of plant biomass in various environments. These microorganisms can be isolated from various environments, such as soils, the insect gut, the mammalian rumen and oceans. The Red Sea exhibits a unique environment in terms of presenting a high seawater temperature, high salinity, low nutrient levels and high biodiversity. However, there is little information regarding cellulase genes in the Red Sea environment. This study aimed to examine whether the Red Sea can be a resource for the bioprospecting of microbial cellulases by isolating cellulase-producing microorganisms from the Red Sea environment and characterizing cellulase genes. Three bacterial strains were successfully isolated from the plankton fraction and the surface of seagrass. The isolated strains were identified as Bacillus paralicheniformis and showed strong cellulase activity. These results suggested that these three isolates secreted active cellulases. By whole genome sequencing, we found 10 cellulase genes from the three isolates. We compared the expression of these cellulase genes under cellulase-inducing and non-inducing conditions and found that most of the cellulase genes were generally upregulated during cellulolysis in the isolates. Our operon structure analysis also showed that cellulase genes form operons with genes involved in various kinds of cellular reactions, such as protein metabolism, which suggests the existence of crosstalk between cellulolysis and other metabolic pathways in the bacterial isolates. These results suggest that multiple cellulases are playing important roles in cellulolysis. Our study reports the isolation and characterization of cellulase-producing bacteria from the Red Sea. Our whole-genome sequencing classified our three isolates as Bacillus paralicheniformis, and we revealed the presence of ten cellulase orthologues in each of three isolates' genomes. Our comparative expression analysis also identified that most of the cellulase genes were upregulated under the inducing conditions in general. Although cellulases have been roughly classified into three enzyme groups of beta-glucosidase, endo-β-1,4-glucanase and exoglucanase, these findings suggest the importance to consider microbial cellulolysis as a more complex reaction with various kinds of cellulase enzymes.


[Malignant melanoma in Puerto Rico].
An epidemiological study of malignant melanoma in Puerto Rico was done by reviewing the Puerto Rico Cancer Registry for all melanoma cases reported between the years 1981 to 1987. A total of 367 new cases were documented with the annual incidence ranging from 1.20 to 2.12 per 100,000 inhabitants with a mean of 1.59. Most of the patients were between 40 and 80 years of age with a peak in the sixties. Nearly one half of the tumors were located on the extremities, most notably on the feet, sharing this predilection with Blacks and Japanese. The most frequently recognized clinico-histologic type was the superficial spreading melanoma followed by the acral lentiginous, the nodular and the lentigo maligna melanoma. Nearly one third of the total cases were not classified according to the histologic type, while Clark's levels and Breslow's thickness were not reported in 44 and 84% of the cases, respectively. When compared to a previous study during 1977 to 1980, the average annual incidence of new cases increased from 0.92 to 1.59 per 100,000 documenting an increased incidence of the condition in our population, but not as significant as that registered in the United States.


Subcutaneous Injection of Triamcinolone and Lidocaine to Prevent Postherpetic Neuralgia.
Herpes zoster (HZ) is associated with inflammation of the peripheral nerves, which is considered to be an important cause of postherpetic neuralgia (PHN). Interventions aimed at reducing this inflammation could prevent PHN. One option is the epidural administration of corticosteroid and local anesthetic. However, several authors have reported a risk of arachnoiditis with epidural corticosteroids. Subcutaneous injection in an outpatient setting is a safer option. However, there is limited evidence of the effectiveness of this alternative for preventing PHN. The aim of this study was to assess the effectiveness of subcutaneous injection of triamcinolone and lidocaine for the prevention of PHN in elderly HZ patients. Randomized, single-center, clinical trial. Department of pain management of a teaching hospital in Beijing, China. Patients with acute HZ with rash < 7 days (n = 100) were randomly assigned to receive either standard therapy (oral antivirals and analgesics) alone or standard therapy plus subcutaneous injection of triamcinolone and lidocaine. The severity of pain was assessed using a numeric rating scale (NRS) at enrollment and at one, 3, and 6 months after rash onset. Quality of life (QoL) was evaluated by the SF-36 before treatment and at 3 and 6 months after rash onset. The primary endpoint was the presence of zoster-associated pain (ZAP) at 3 months after rash onset. At enrollment, all patients reported ZAP with average NRS scores of 6.64 ± 1.44 and 7.16 ± 1.22 in the standard group and subcutaneous group, respectively. At 3 and 6 months after rash onset, the pain had decreased in both groups, but the decrease was significantly greater in the subcutaneous injection group. At 3 months, 2 (4%) patients in the subcutaneous injection group vs. 10 (20%) patients in the standard group had ZAP with NRS > 3 (P = 0.014). Both groups showed significant improvement in QoL at 3 and 6 months. No patient had major adverse events related to the subcutaneous injection. The main limitation of the study was the absence of a placebo subcutaneous injection in the standard group. Subcutaneous injection of triamcinolone and lidocaine in the acute phase of HZ can reduce ZAP more effectively than oral antivirals and analgesics alone, and may be a feasible method to prevent PHN. Subcutaneous injection, lidocaine, triamcinolone, postherpetic neuralgia, prevention.


Decision-making, barriers, and facilitators regarding cervical cancer screening participation among Turkish and Moroccan women in the Netherlands: a focus group study.
OBJECTIVES: Whether the lower Dutch cervical cancer (CC) screening participation of Turkish- and Moroccan-Dutch women is based on informed decision-making is unknown. Our aim was to explore how and why Turkish- and Moroccan-Dutch women decide to participate or not in the current Dutch CC screening programme as well as to learn their perceptions on self-sampling.DESIGN: Six focus group discussions were conducted between March and April 2019 with Turkish (n = 24) and Moroccan (n = 20) women in the Netherlands, aged 30-60 years. Questions were based on an extended version of the Health Belief Model. Discussions were transcribed verbatim and thematically analysed.RESULTS: Participants lacked knowledge about CC and its screening, and seemed to be unaware of the cons of CC screening. Perceived barriers for screening were lack of a good command of the Dutch language, having a male general practitioner, fatalism, shame and taboo, and associations of CC with lack of femininity and infertility. Other barriers were fear of the test result, cancer, suffering, death, and leaving their children behind after death. Perceived facilitators were a high perceived severity of disease, social support, and short procedure time. An additional religious facilitator included the responsibility to take care of one's own health using medical options that God provided. Participants had low self-efficacy expectations towards performing correct self-sampling.CONCLUSIONS: Although participants' informed-decision making seems to be limited, this study showed that women do not only consider factual medical information, but also practical, emotional, cultural, and religious aspects prior to deciding to screen or not. Information materials should be tailored to these aspects, as well as translated to appropriate languages due to lack of a good command of the Dutch language. Self-efficacy expectations towards performing correct self-sampling should be enhanced to promote informed CC screening participation among Turkish- and Moroccan-Dutch women.


[Research about improving flowability of powder of Chinese herbs extracts by surface modification technology].
In this study, modification technology by surface coating was used to improve the flowability of powder of Chinese herbs extracts. Seven kinds of powder of Chinese herbs extracts were coated with 1% silica nanoparticles using an under-driven Comil. The powder characteristics tester was used to evaluate the flowability of uncoated and coated powders. Surface morphology and particle size distribution of powders were compared by scanning electron microscope (SEM) and optical microscope. The powder hygroscopicity was also investigated. The results showed that, after modification, angle of repose, angle of spatula, compressibility and adhesiveness extremely decreased, and flowability index substantially increased, the powder flowability was significantly improved, especially Gegen and Dahuang extracts powders. Scanning electron microscopy images showed the distribution of silica nanoparticles on the host drug particle surfaces. There were no remarkable changes in the particle size distribution and hygroscopicity of all powders after coating. Therefore, Comilling for surface coating modification technology was an effective method to improve the flowability of Chinese herbs extracts and suggested a possible way forward to enhance the quality of Chinese drugs pharmaceutics in their study and manufacture.


Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene.
Stress response elements, which mediate induction of the mouse heme oxygenase-1 (HO-1) gene by several agents, resemble the binding site for the activator protein-1 (Jun/Fos), Maf, and Cap'n'Collar/basic leucine zipper (CNC-bZIP) families of proteins. In L929 fibroblasts, significant activation of an HO-1 enhancer-reporter fusion gene was observed only with the CNC-bZIP class of proteins with Nrf2 exhibiting the highest level of trans-activation, between 25- and 30-fold. To further examine the role of this factor in HO-1 gene regulation, a dominant-negative mutant, Nrf2M, was generated and conditionally expressed in L929 cells. The mutant protein was detected in cytoplasmic and nuclear fractions but did not affect cell growth. Under conditions of Nrf2M overexpression, HO-1 mRNA accumulation in response to heme, cadmium, zinc, arsenite, and tert-butylhydroquinone was inhibited by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun decreased L929 cell growth but did not inhibit HO-1 gene activation. Nrf2 does not homodimerize, but CNC-bZIP.small Maf protein heterodimers and Nrf2. Jun protein complexes are proposed to function as trans-activators. Co-expression of Jun proteins or p18, however, had no significant affect or inhibited Nrf2-mediated trans-activation. Taken together, these results implicate Nrf2 in the induction of the HO-1 gene but suggest that the Nrf2 partner in this function is a factor other than p18 or Jun proteins.


Infection by Cag A positive strains of Helicobacter pylori is associated with autoimmune thyroid disease in Iranian patients.
Infectious agents have been suspected as a triggering factor for development of autoimmune thyroid disease (ATD). Some reports from Western countries have suggested association between Helicobacter pylori (HP) infection and ATD. To investigate the association of ATD with Cag A seropositivity in a population with high rate and early age of onset of HP infection. IgG anti HP and anti Cag A antibodies were measured in 88 patients with ATD and compared with results of 112 healthy individuals. The rate of infection with HP was not significantly different in patient and control groups, but there was significant association between ATD and infection with Cag A strains (p<0.005). This association was significant for both hypothyroidism (p<0.005) and Graves' disease (p<0.02). Cag A antibody level correlated with titers of thyroid auto antibodies (p<0.001). In a population with high rate and early age of onset of HP infection, only infection with Cag A positive strains is associated with ATD, and this may be due to immune cross-reactivity.


Electron microscopy of frozen-hydrated bacteria.
Amorphous, unstained, frozen-hydrated sections of bacteria provide a faithful high-resolution image of procaryotic cells. Conventional preparation artifacts due to fixation, staining, and dehydration are nonexistent. Freezing damage is avoided by using glucose as a cryoprotectant. Cutting damage on frozen material is severe, but sectioning artifacts, being always related to the cutting direction, can be systematically recognized and thus taken into consideration. Geometry and density distribution of the bacterial envelope can be resolved to about 3 nm. The following main features have been observed. In Escherichia coli the inner and outer membranes have an approximately uniform density profile. The distance between the two membranes is constant, ca. 33 nm. In Staphylococcus aureus the cell wall is ca. 40 nm wide. It is bordered on the cytoplasmic side by an asymmetric 5.5-nm-wide bilayer. The bacterial nucleoid, clearly visible with conventional preparation methods, appears in exponentially growing bacteria as an ill-defined central region with approximately the same density as the rest of the cytoplasm. It becomes more clearly visible when bacteria are in the stationary phase, plasmolysed, fixed, or stained. We confirm that "mesosomes," hitherto quite often considered to be essential organelles in all procaryotes, are artifacts. They appear in large numbers during osmium fixation.


Type 1b Endoleaks After Thoracic Endovascular Aortic Repair are Inadequately Reported: A Systematic Review.
Complications after thoracic endovascular aortic repair (TEVAR) are common. Even after a successful TEVAR, a late endoleak (>30 days) can occur. The objective of this study is to summarize the current evidence and, if lacking, the need of evidence regarding the incidence and predictive factors for type 1b endoleak in patients with aortic aneurysm treated with TEVAR. A systematic review of the literature was performed on endoleak type 1b, in patients with aortic aneurysm, after TEVAR. The PubMed and Embase databases were systematically searched for articles regarding endoleak type 1b up to January 2019. The main subjects discussed are the incidence, risk factors, treatment, and prognosis. About 722 articles were screened, and 16 articles were included in this review. The reported incidence of endoleak is between 1.0% and 15.0%, with a mean follow-up duration of at least 1 year. Type 1b endoleak is associated with an increased aortic tortuosity index (>0.15 cm-1). No significant difference is found in relation to age and gender. Treatment is required in most cases (22/27) and is usually performed with distal extension of the stent graft (21/27). There are no data regarding stent graft oversizing, length of distal landing zone, and differences between devices or the prognosis for patients with type 1b endoleak. Limited literature is available on the occurrence of type 1b endoleak after TEVAR. A tortuous aorta can be associated as a predictive factor for the occurrence of type 1b endoleak. Data clearly delineating the anatomic variables predicting type 1b endoleak should be examined and listed. Likewise, the impact of more recent conformable devices to prevent complications like type 1b endoleaks from occurring should be elucidated.


Presence of a tumour-inhibiting factor (TIF) in sera from normal but not tumour-bearing mice.
Some plasmacytomas produce myeloma proteins with known antibody specificities and the secretion of these proteins by individual tumour cells can be determined using haemolytic plaque assay. After a 3 day culture of mouse plasmacytoma cells in medium containing 10% normal mouse serum, the number of plaques was reduced to less than 10% when compared to that of tumour cells incubated with either foetal calf serum or normal rabbit serum. However, tumour cells incubated with sera from mice bearing TEPC-15, McPC-603, or MOPC-315 plasmacytomas displayed control levels of plaques. The production of plaques paralleled the viability of tumour cells suggesting that the reduction of plaque formation is due to the decreased viable cell number. The tumour-inhibiting activity was recovered from the fraction of apparent molecular weight of 300,000-400,000 after a partial purification using an agarose (A 0.5 M) column. This fraction, however, did not suppress in vitro induction of antibody production. Kinetic experiments using sera obtained sequentially from individual mice receiving either TEPC-15 or MOPC-315 plasmacytomas further indicated that the tumour-inhibiting activity is severely reduced during a 2 week period after tumour inoculation. The inhibition of tumour cells did not appear to be specific since tumour cells of three plasmacytomas (TEPC-15, MOPC-167 and MOPC-315), a mastocytoma (P815) and a lymphoma (EL-4) displayed a similar susceptibility to normal serum.


Interactions of waterborne and dietary cadmium on the expression of calcium transporters in the gills of rainbow trout: influence of dietary calcium supplementation.
Recent studies have shown that dietary Ca(2+) supplementation strongly inhibits uptake of Ca(2+) and Cd at the fish gill. To better understand the influence of dietary Ca(2+) on branchial Ca(2+) transport, we examined the expression of two trout gill calcium transporters during waterborne and dietary Cd exposure, at two different levels of dietary Ca(2+). Quantitative polymerase chain reaction (PCR) was used to monitor epithelial calcium channel (ECaC) and sodium-calcium exchange (NCX) mRNA levels following 7-28 days of exposure to these treatments. In brief, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to control, 3 microg/L waterborne Cd, 500 mg/kg dietary Cd, or a combined 3 microg/L waterborne plus 500 mg/kg dietary Cd exposure, supplemented with either 20 mg/g or 60 mg/g dietary calcium (Ca(2+)). Two-way analysis of variance was used to discern the main effects of Cd exposure and dietary Ca(2+) supplementation on ECaC and NCX mRNA levels. We found that dietary Ca(2+) supplementation decreased significantly ECaC mRNA expression on days 14 and 21. In comparison, NCX mRNA levels were not influenced by dietary Ca(2+) supplementation, but rather were significantly inhibited in the combined waterborne and dietary Cd exposure on day 7 alone. Statistical analysis found no interactive effects between Cd exposure and dietary Ca(2+) exposure at any time point, except for day 28. This study provides evidence of the importance of nutritional status on the transcriptional regulation of ion transport at the fish gill. We discuss the importance of diet and nutritional status to the development of new regulatory approaches, such as the biotic ligand model, which currently do not account for the significance of diet on metal bioavailability in aquatic organisms.


The benefits of implant removal from the foot and ankle.
Following successful orthopaedic surgical procedures, implant removal is generally not necessary or recommended. However, patients with pain related to implants may benefit from this elective procedure. The foot and ankle may be more symptomatic from retained implants because of weight-bearing activities, shoe wear, and limited soft-tissue cushioning. In such cases, implant removal may provide good and reliable relief of symptoms. A prospective study of sixty-nine patients who underwent elective removal of symptomatic implants from the foot and ankle was undertaken to evaluate the patients' pain experience. The short-form McGill pain questionnaire was administered preoperatively and six weeks postoperatively. Postoperatively, patients were also asked whether they would repeat the procedure and whether they were satisfied with the results. Patients reported significantly less pain following the procedure, with the average rating of pain on the visual analog scale (VAS) decreasing from 3.06 to 0.88 and the average rating of present pain intensity decreasing from 2.03 to 0.58 (p < 0.05 for both). Sixty-five percent of the patients reported no pain on either measure at six weeks postoperatively. Preoperative pain was correlated with postoperative pain (r = 0.24 and p < 0.05 for VAS, and r = 0.16 and p > 0.05 for present pain intensity).With the small sample size, preoperative and postoperative pain did not show a significant difference on the basis of implant location or patient age or sex. Ninety-four percent of patients said they would repeat the procedure under the same circumstances, and 91% of patients were satisfied with the results. Following successful orthopaedic surgical procedures, removal of implants causing symptoms can result in pain relief and a high rate of patient satisfaction. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer.
Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range of cancer types. A lack of published work using therapeutic modalities has precluded the testing of the hypothesis that blocking the gremlin-1/BMP interaction will provide benefits to patients. To address this shortfall, we developed ginisortamab (UCB6114), a first-in-class clinical anti-human gremlin-1 antibody, currently in clinical development for the treatment of cancer, along with its murine analog antibody Ab7326 mouse immunoglobulin G1 (mIgG1). Surface plasmon resonance assays revealed that ginisortamab and Ab7326 mIgG1 had similar affinities for human and mouse gremlin-1, with mean equilibrium dissociation constants of 87 pM and 61 pM, respectively. The gremlin-1/Ab7326 antigen-binding fragment (Fab) crystal structure revealed a gremlin-1 dimer with a Fab molecule bound to each monomer that blocked BMP binding. In cell culture experiments, ginisortamab fully blocked the activity of recombinant human gremlin-1, and restored BMP signaling pathways in human colorectal cancer (CRC) cell lines. Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298).


Are rural places less safe for motorists? Definitions of urban and rural to understand road safety disparities.
The objectives of the study are to understand road safety within the context of regional development processes and to assess how urban-rural categories represent differences in motor vehicle occupant fatality risk. We analysed 2015 motor vehicle occupant deaths in Wisconsin from 2010 to 2014, using three definitions of urban-rural continua and negative binomial regression to adjust for population density, travel exposure and the proportion of teen residents. Rural-Urban Commuting Area codes, Beale codes and the Census definition of urban and rural places do not explain differences in urban and rural transportation fatality rates when controlling for population density. Although it is widely believed that rural places are uniquely dangerous for motorised travel, this understanding may be an artefact of inaccurate constructs. Instead, population density is a more helpful way to represent transportation hazards across different types of settlement patterns, including commuter suburbs and exurbs.


From Land to Sea; Embracing a Renewable Future.
The authors discuss the ever increasing role of biological renewable resources in energy, nutrition, and pharmaceuticals; specifically those potentially available deep within the oceans. They provide a list of products already gleaned from this vastly untapped marine environment; discuss the innovations in technology required to effectively explore and prospect the deeper reaches of the ocean; expose the impressive contribution to the economy; and expound the paramount importance of protecting the oceans to ensure the future. Already many new proteins, enzymes, and pharmaceuticals are being developed from the fauna and flora of the forests and relatively shallow economic zones of the ocean. With much of the ocean still an unexplored frontier, the authors hope to promote increased interest in research and development in this arena.


Effects of vibration training on force production in female basketball players.
The goal of this research project was to investigate the long-term effects of whole-body vibration (WBV) training on force production. Thirty-one female basketball players were randomly distributed in an experimental group: VG (vibration) and a control group: CG (no vibration). Both groups participated in the same training program; however, the experimental group (VG) performed a set of exercises on a vibration platform (Power Plate) at 30- to 35-Hz frequency and 4 mm amplitude, whereas the CG performed the same exercises at 0 Hz. Muscle performance of the legs was tested on a contact-time platform (Ergojump, Finland) through several tests: squat jump (SJ), countermovement jump (CMJ), and 15-second maximal performance jump; squat leg power (knee extension) was also evaluated using an Ergopower machine (Bosco, Italy). After 14 weeks, there was a significant increase (p < 0.001) from initial to final tests in both groups (CG and VG) in SJ, CMJ, 15 seconds, and squat leg power. However, there were no significant differences between the VG and the CG for any of the parameters evaluated. The findings of this study indicate that WBV training has no additive or discernible effect on the strength development of female basketball players after several weeks of use, suggesting that the application of this technology has no advantages over traditional strength training methods.


Increased dietary salt intake enhances the exercise pressor reflex.
Increased dietary salt in rats has been shown to sensitize central sympathetic circuits and enhance sympathetic responses to several stressors, including hyperinsulinemia, intracerebroventricular injection of angiotensin, and electrical stimulation of sciatic nerve afferents. These findings prompted us to test the hypothesis that increased dietary salt enhanced the exercise pressor reflex. Male Sprague-Dawley rats were fed 0.1% (low) or 4.0% (high) NaCl chow for 2 to 3 wk. On the day of the experiment, the rats were decerebrated, and the hind limb muscles were statically contracted for 30 s by electrically stimulating the cut peripheral ends of the L4 and L5 ventral roots. We found that contraction produced a significantly greater increase in mean arterial pressure of rats fed 4.0% (n = 26) vs. 0.1% (n = 22) NaCl (24 ± 2 vs. 15 ± 2 mmHg, respectively; P < 0.05). Baseline mean arterial pressure was not different between groups (0.1%, 77 ± 4 vs. 4.0% NaCl, 80 ± 3 mmHg). Likewise, the tension time indexes were not different between the two groups (P = 0.42). Section of the L4 and L5 dorsal roots greatly attenuated both the pressor and cardioaccelerator responses to contraction in both groups of rats, an effect showing that the responses were reflex in origin. Finally, electrical stimulation of the lumbar sympathetic chain produced similar increases in mean arterial pressure and decreases in femoral arterial blood flow and conductance between rats fed 0.1% vs. 4.0% NaCl diets. We conclude that increased dietary salt enhances the exercise pressor reflex.


Variation in pigments in pecan testa during kernel development and storage.
The pecan (Carya illinoinensis) is an important tree nut worldwide. Browning of the testa during storage considerably reduces its quality. However, the pigments that cause browning and their accumulation patterns are poorly understood. We analyzed the color changes in the testa during the five developmental stages of the kernel after storage at room temperature to compare differences in their color and identify the pigments. Samples exhibiting different colors along with their corresponding -80 °C storage samples were selected for metabolomic analysis. A total of 591 phenolic compounds were detected, 52 phenolics showed regulatory effects on testa discoloration, and 59 metabolites were identified as possible precursors of the pigments. This study revealed the most thorough phenolic composition of pecan to date. Further, the findings provide new insights into the mechanisms of testa browning, deepens our understanding of the bioactive value of pecans, and contributes to the breeding of less browning-susceptible varieties.


Localized bacterial infection induces systemic activation of neutrophils through Cxcr2 signaling in zebrafish.
Neutrophils are the first line of defense against tissue damage and are rapidly mobilized to sites of bacterial infection. However, the signals that regulate neutrophil recruitment are not well defined. Here, using photolabel-enabled fate mapping in zebrafish larvae, we show that localized otic infection with Pseudomonas aeruginosa induces systemic activation and mobilization of neutrophils from the CHT through Cxcr2 signaling. We have cloned the zebrafish Cxcr1 and Cxcr2 receptors and show that Cxcr2 functions as a Cxcl8 receptor in live zebrafish. With the use of morpholino-mediated depletion, we show that infection-induced neutrophil mobilization from the CHT is mediated by Cxcr2 but not Cxcr1. By contrast, Cxcr2 depletion does not affect neutrophil recruitment to the chemoattractant LTB4. Taken together, our findings identify Cxcl8-Cxcr2 signaling as an infection-induced long-range cue that mediates neutrophil motility and mobilization from hematopoietic tissues, positioning Cxcr2 as a critical pathway that mediates infection-induced systemic activation of neutrophils.


Metallothioneins (MTs) in the human eye: a perspective article on the zinc-MT redox cycle.
Metallothioneins (MTs) are zinc-ion-binding proteins with a wide range of functions, among which are neuroprotection, maintenance of cellular zinc homeostasis, and defense against oxidative damage and inflammation. The human eye is enriched in MTs, and multiple isoforms may contribute to distinct antioxidant defense mechanisms in various ocular tissues. Zinc is a main regulator of MT gene and protein expression, and we recently applied bioanalytical techniques to address key questions on its relationship with MTs, including the stoichiometry of zinc-MT, the fate of zinc tracers ((nat)Zn and (68)Zn) in MTs during activation by exogenous zinc and cytokines, and the concentration of MTs in human ocular cells. We found that exogenously introduced zinc induced a potent de novo synthesis of MTs as well as a strong inhibition of pro-inflammatory cytokines. Zinc and cytokines also promote a stoichiometric transition of the MT complex from Zn6Cu1-MT to Zn7-MT, suggesting that MTs may interact more effectively with reactive oxygen species to decrease potential oxidative damage. Levels of MTs decrease with aging and disease, which may result in zinc release that is potentially cytotoxic. This state is also observed with increased oxidative stress and inflammation, suggesting that the antioxidant function of MTs has been impaired. In this review we propose a working model of the "zinc-metallothionein redox cycle" to regenerate and enhance the antioxidant function of MTs with the aim of combating the progression of these disease states.


[Effect of chalone-containing aorta extracts on regression in experimental atherosclerosis].
The effect of chalone-containing aortic extracts on proliferative activity of smooth muscle cells was examined in conditions of experimental hypercholesterolemia. The tissue-specific cell proliferation inhibitor present in the extract is shown to depress mitotic activity of smooth muscle cells in postnatal rats. The area under aortic atherosclerotic lesion diminished twofold as compared to that of the controls. Morphologically, atherosclerotic changes are seen as lipid plaques.


Serum T3 and T4 concentrations in the adult rats treated with herbicide 2,4-dichlorophenoxyacetic acid.
The influence of sublethal doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on serum T3 and T4 concentrations in Hsd Cpb: Wistar rats of both sexes was studied. The trial was performed on 24 males and females respectively, each divided into three groups of 8 animals (control, groups 1 and 2). Aqueous solution of the compound (11 mg/kg body weight--group 1 and 110 mg/kg body weight--group 2) or clean tap water (control group) was used. Aliquots of 2.4 ml/kg body weight were administered with a stomach tube from the 1st to 10th day of the experiment. Three days before the first treatment and on the 6th and 13th day of the experiment the serum T3 and T4 concentrations were determined by commercial radioimmunoassay kits (Byk-Sangtec Diagnostica), validated for rats. A significant decrease of serum T4 (P < 0.01) and T3 (P < 0.001) was determined in males of groups 1 and 2 during the experiment. On the 6th day of experiment serum T4 and T3 values were significantly lower (P < 0.001 and 0.01 respectively) in group 2 than in the controls and group 1 of both males and females. During the whole experiment serum T4 levels were lower in females than in males (P < 0.05).


Multiplexed genome engineering by Cas12a and CRISPR arrays encoded on single transcripts.
The ability to modify multiple genetic elements simultaneously would help to elucidate and control the gene interactions and networks underlying complex cellular functions. However, current genome engineering technologies are limited in both the number and the type of perturbations that can be performed simultaneously. Here, we demonstrate that both Cas12a and a clustered regularly interspaced short palindromic repeat (CRISPR) array can be encoded in a single transcript by adding a stabilizer tertiary RNA structure. By leveraging this system, we illustrate constitutive, conditional, inducible, orthogonal and multiplexed genome engineering of endogenous targets using up to 25 individual CRISPR RNAs delivered on a single plasmid. Our method provides a powerful platform to investigate and orchestrate the sophisticated genetic programs underlying complex cell behaviors.


Calcium-channel blocking and nanoparticles-based drug delivery for treatment of drug-resistant human cancers.
Cancer cell chemoresistance is one of the major limitations to successful cancer treatment and one of the factors that is responsible for the possible recurrence of the disease. Here, we aimed to combine a calcium-channel blocker, verapamil, with an alternative delivery of the anti-cancer drug, doxorubicin, using nanostructural materials. This approach could reduce the cellular resistance to chemotherapeutics agents. The outcome of this complex approach on cellular viability was investigated by using various assays in both a time- and concentration-dependent manner: WST-1, flow cytometry cell viability assay, fluorescence microscopy, DNA fragmentation, and TUNEL labeling of apoptotic cells. All of these analytical assays confirmed the ability to reduce the chemoresistance of the cancer cells based on the proposed procedure.


Peripheral neuropathy associated with monoclonal gammopathy. Studies of intraneural injections of monoclonal immunoglobulin sera.
A causal relationship between paraproteinemia and neuropathies has been suggested. We studied three patients with chronic sensorimotor polyneuropathy associated with plasma cell dyscrasia and monoclonal gammopathies (IgGK, IgMK, IgA lambda). Sural nerve biopsies showed mild (2 cases) to moderate loss of myelinated fibers (1 case). Teased single fiber studies showed segmental demyelination-remyelination in two patients. Direct immunofluorescence demonstrated immune deposits of the myelin sheath of the same specificity as the serum paraprotein, IgGK (1 of 3 cases). Treatment with prednisone, melphalan or chlorambucil, and plasmapheresis resulted in remission (1 case), partial improvement (1 case), or had no effect (1 case), although reduction of monoclonal immunoglobulin occurred in all. To investigate the role the paraproteins might play in the pathogenesis of the neuropathy, patients' serum was injected intraneurally into rat sciatic nerves. None of the animals developed weakness, slowing of in vitro conduction of sciatic nerve, or significant evidence of demyelination by light- or electron-microscopy or teased single fiber studies 48 hours postinjection. Similar injections of rabbit serum with experimental allergic neuritis (EAN) produced focal segmental demyelination. Our studies employing an in vivo bioassay technique failed to establish antimyelin activity of monoclonal immunoglobulin sera.


Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy.
Traditional magnetic resonance (MR) imaging can identify abnormal changes in ipsilateral thalamus in patients with unilateral middle cerebral artery (MCA) infarcts. However, it is difficult to demonstrate these early changes quantitatively. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (MRS) are potentially sensitive and quantitative methods of detection in examining changes of tissue microstructure and metabolism. In this study, We used both DTI and MRS to examine possible secondary damage of thalamus in patients with corona radiata infarction. Twelve patients with unilateral corona radiata infarction underwent MR imaging including DTI and MRS at one week (W1), four weeks (W4), and twelve weeks (W12) after onset of stroke. Twelve age-matched controls were imaged. Mean diffusivity (MD), fractional anisotropy (FA), N-acetylaspartate (NAA), choline(Cho), and creatine(Cr) were measured in thalami. T1-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted, and T2-FLAIR imaging showed an infarct at unilateral corona radiate but no other lesion in each patient brain. In patients, MD was significantly increased at W12, compared to W1 and W4 (all P< 0.05). NAA was significantly decreased at W4 compared to W1, and at W12 compared to W4 (all P< 0.05) in the ipsilateral thalamus. There was no significant change in FA, Cho, or Cr in the ipsilateral thalamus from W1 to W12. Spearman's rank correlation analysis revealed a significant negative correlation between MD and the peak area of NAA, Cho, and Cr at W1, W4, and W12 and a significant positive correlation of FA with NAA at W1. These findings indicate that DTI and MRS can detect the early changes indicating secondary damage in the ipsilateral thalamus after unilateral corona radiata infarction. MRS may reveal the progressive course of damage in the ipsilateral thalamus over time.


Development of a Model Care Pathway for Myasthenia Gravis.
Myasthenia Gravis (MG) is a chronic, life-lasting condition that requires high coordination among different professionals and disciplines. The diagnosis of MG is often delayed and sometimes misdiagnosed. The goal of the care pathway (CP) is to add value to healthcare reducing unnecessary variations. The quality of the care received by patients affected with MG could benefit from the use of CP. We conducted a study aimed to define an inclusive, comprehensive, and multidisciplinary CP for the diagnosis, treatment, and care of MG. The development of the model CP, key interventions, and process indicators is based on the literature review and 85 international MG experts were involved in their evaluation, expressing a judgment of relevance through the Delphi study. 60 activities are included in the model CP and evaluated by the MG experts were valid and feasible. The 60 activities were then translated into 14 key interventions and 24 process indicators. We believe that the developed model CP will help for MG patients to have a timely diagnosis and high-quality, accessible, and cost-effective treatments and care. We also believe that the development of model CPs for other rare diseases is feasible and could aid in the integration of evidence-based knowledge into clinical practice.


Monitoring the remediation of groundwater polluted by MSW landfill leachates by activated carbon and zeolite with spectral induced polarization technique.
The municipal solid waste (MSW) landfill in Hangzhou, China utilized zeolite and activated carbon (AC) as permeable reactive barrier (PRB) fill materials to remediate groundwater contaminated with MSW leachates containing ammonium, chemical oxygen demand (COD), and heavy metals. The spectral induced polarization (SIP) technique was chosen for monitoring the PRB because of its sensitivity to pore fluid chemistry and mineral-fluid interface composition. During the experiment, authentic groundwater collected from the landfill site was used to permeate two columns filled with zeolite and AC, and the SIP responses were measured at the inlet and outlet over a frequency range of 0.01-1000 Hz. The results showed that zeolite had a higher adsorption capacity for COD (7.08 mg/g) and ammonium (9.15 mg/g) compared to AC (COD: 2.75 mg/g, ammonium: 1.68 mg/g). Cation exchange was found to be the mechanism of ammonium adsorption for both zeolite and AC, while FTIR results indicated that π-complexation, π-π interaction, and electrostatic attraction were the main mechanisms of COD adsorption. The Cole-Cole model was used to fit the SIP responses and determine the relaxation time (τ) and normalized chargeability (mn). The calculated characteristic diameters of zeolite and AC based on the Schwarz equation and relaxation time (τ) matched the pore sizes observed from SEM and MIP, providing valuable information on contaminant distribution. The mn of zeolite was positively linear with adsorbed ammonium (R2 = 0.9074) and COD (R2 = 0.8877), while the mn of AC was negatively linear with adsorbed ammonium (R2 = 0.8192) and COD (R2 = 0.7916), suggesting that mn could serve as a surrogate for contaminant saturation. The laboratory-based real-time non-invasive SIP results showed good performance in monitoring saturation and provide a strong foundation for future field PRB monitoring.


Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics.
Recent studies have reported an increased risk of second primary malignancies (SPM) following multiple myeloma (MM) diagnosis associated with novel anti-myeloma treatments. We evaluated the risk of SPM among 36 491 MM cases reported to the Surveillance, Epidemiology, and End Results program (SEER) between 1973 and 2008. We calculated overall and site-specific standardized incidence ratio (SIR) and 95% confidence intervals (CI) for 2012 SPM cases diagnosed within the 35-year follow-up. There was no significant overall risk of SPM (SIR=0.98; 95% CI=0.94-1.02); however, there were multiple site-specific risk patterns. The risk of breast and prostate cancer was significantly decreased overall and across age, latency and the year of diagnosis strata. There was an ∼50% increased risk of colorectal cancer 5 years after MM diagnosis (Ptrend<0.001). The risk of hematological malignancies was significantly increased, notably for acute myeloid leukemia (AML; SIR=6.51; 95% CI=5.42-7.83). There was a significant decreasing trend for AML over time, particularly for patients 65. However, no significant change in risk was noted after the introduction of autologous stem cell transplant among younger patients (<65 years). On the basis of observed trends for overall SPM as well as AML, no association between the introduction of novel therapies and SPM following MM has emerged in this large population-based study.


[Tissue engineering in urology. Basic principles and application].
Tissue engineering is a rather new field of science. Despite this fact, some experimental investigations have already been applied in clinical studies. Compared to other medical fields, tissue engineering in urology is well established. Tissue-engineered bulking agents and tissue-engineered bladder augments are being investigated in clinical trials. Even though the knowledge gained in recent years is promising, the results of cellular therapies need to be critically judged before being finally applied in patients. Genetic engineering and stem cell research (adult undifferentiated cells) have had major impact on the field of tissue engineering over the past 2 years. By using the technology of genetic engineering, biochemical and functional qualities of tissues may be modified. Adult stem cells may help to substitute lost tissue in an autologous fashion by isolating undifferentiated cells from the body and by differentiating them into a desired cell type. These cells may be used to form native functional tissue to replace a diseased organ or organ part.


Quantifying Unmet Need in Statin-Treated Hyperlipidemia Patients and the Potential Benefit of Further LDL-C Reduction Through an EHR-Based Retrospective Cohort Study.
Statins are effective in helping prevent cardiovascular disease (CVD). However, studies suggest that only 20%-64% of patients taking statins achieve reasonable low-density lipoprotein cholesterol (LDL-C) thresholds. On-treatment levels of LDL-C remain a key predictor of residual CVD event risk. To (a) determine how many patients on statins achieved the therapeutic threshold of LDL-C < 100 mg per dL (general cohort) and < 70 mg per dL (secondary prevention cohort, or subcohort, with preexisting CVD); (b) estimate the number of potentially avoidable CVD events if the threshold were reached; and (c) forecast potential cost savings. A retrospective, longitudinal cohort study using electronic health record data from the Indiana Network for Patient Care (INPC) was conducted. The INPC provides comprehensive information about patients in Indiana across health care organizations and care settings. Patients were aged > 45 years and seen between January 1, 2012, and October 31, 2016 (ensuring study of contemporary practice), were statin-naive for 12 months before the index date of initiating statin therapy, and had an LDL-C value recorded 6-18 months after the index date. Subsequent to descriptive cohort analysis, the theoretical CVD risk reduction achievable by reaching the threshold was calculated using Framingham Risk Score and Cholesterol Treatment Trialists' Collaboration formulas. Estimated potential cost savings used published first-year costs of CVD events, adjusted for inflation and discounted to the present day. Of the 89,267 patients initiating statins, 30,083 (33.7%) did not achieve the LDL-C threshold (subcohort: 58.1%). In both groups, not achieving the threshold was associated with patients who were female, black, and those who had reduced medication adherence. Higher levels of preventive aspirin use and antihypertensive treatment were associated with threshold achievement. In both cohorts, approximately 64% of patients above the threshold were within 30 mg per dL of the respective threshold. Adherence to statin therapy regimen, judged by a medication possession ratio of ≥ 80%, was 57.4% in the general cohort and 56.7% in the subcohort. Of the patients who adhered to therapy, 23.7% of the general cohort and 50.5% of the subcohort had LDL-C levels that did not meet the threshold. 10-year CVD event risk in the at-or-above threshold group was 22.78% (SD = 17.24%) in the general cohort and 29.56% (SD = 18.19%) in the subcohort. By reducing LDL-C to the threshold, a potential relative risk reduction of 14.8% in the general cohort could avoid 1,173 CVD events over 10 years (subcohort: 15.7% and 454 events). Given first-year inpatient and follow-up costs of $37,300 per CVD event, this risk reduction could save about $1,455 per patient treated to reach the threshold (subcohort: $1,902; 2017 U.S. dollars) over a 10-year period. Across multiple health care systems in Indiana, between 34% (general cohort) and 58% (secondary prevention cohort) of patients treated with statins did not achieve therapeutic LDL-C thresholds. Based on current CVD event risk and cost projections, such patients seem to be at increased risk and may represent an important and potentially preventable burden on health care costs. Funding support for this study was provided by Merck (Kenilworth, NJ). Chase and Boggs are employed by Merck. Simpson is a consultant to Merck and Pfizer. The other authors have nothing to disclose.


Interactions between bacteria and plant-parasitic nematodes: now and then.
Based on genome-to-genome analyses of gene sequences obtained from plant-parasitic, root-knot nematodes (Meloidogyne spp.), it seems likely that certain genes have been derived from bacteria by horizontal gene transfer. Strikingly, a common theme underpinning the function of these genes is their apparent direct relationship to the nematodes' parasitic lifestyle. Phylogenetic analyses implicate rhizobacteria as the predominant group of 'gene donor' bacteria. Root-knot nematodes and rhizobia occupy similar niches in the soil and in roots, and thus the opportunity for genetic exchange may be omnipresent. Further, both organisms establish intimate developmental interactions with host plants, and mounting evidence suggests that the mechanisms for these interactions are shared too. We propose that the origin of parasitism in Meloidogyne may have been facilitated by acquisition of genetic material from soil bacteria through horizontal transfer, and that such events represented key steps in speciation of plant-parasitic nematodes. To further understand the mechanisms of horizontal gene transfer, and also to provide experimental tools to manipulate this promising bio-control agent, we have initiated a genomic sequence of the bacterial hyper-parasite of plant parasitic nematodes, Pasteuria penetrans. Initial data have established that P. penetrans is closely related to Bacillus spp., to the extent that considerable genome synteny is apparent. Hence, Bacillus serves as a model for Pasteuria, and vice versa.


Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid.
Clinical applications of the first-generation multidrug resistance (MDR) modulators, such as cyclosporin A (CsA) have been hampered because of their severe side effects in vivo. In this study, we utilized liposomes and Intralipid to provide selective delivery of CsA to tumor cells as well as to circumvent toxicities associated with CsA by altering the pharmacodistribution properties of encapsulated CsA. The MDR reversing effect of CsA in free, liposomal or Intralipid formulations on the uptake and transport of epirubicin in Caco-2 cells and rat intestines was evaluated. The results showed that CsA in free or liposomal formulations significantly enhanced the intracellular accumulation of epirubicin in a dose-related fashion in Caco-2 cells, with the highest enhancement at 2 microM: These formulations substantially ameliorated the apical to basolateral absorption of epirubicin in Caco-2 cells and markedly increased mucosal to serosal absorption of epirubicin in rat jejunum and ileum. CsA in free, liposomal or Intralipid formulations all significantly reduced basolateral to apical efflux of epirubicin across Caco-2 monolayers. CsA encapsulated in liposomes showed greater enhancement than other formulations. In conclusion, liposomal preparations of CsA may circumvent MDR and have the advantage of diminishing side effects, thus providing a useful alternative dosage form for intravenous administration of CsA to be combined with cytotoxic agents for the treatment of resistant tumors.


Trastuzumab regulates IGFBP-2 and IGFBP-3 to mediate growth inhibition: implications for the development of predictive biomarkers for trastuzumab resistance.
Activation of insulin-like growth factor-I receptor (IGF-IR) signaling is an important mechanism for trastuzumab resistance. IGF-binding proteins (IGFBP) modulate IGF-IR signaling and play important roles in the control of breast cancer progression. In this article, we report that trastuzumab treatment enhances the expression and secretion of IGFBP-3 in SKBR3 cells, a trastuzumab-sensitive breast cancer cell line, and that this upregulation of IGFBP-3 induced by trastuzumab correlates with trastuzumab-mediated growth inhibition. We describe a new role for IGFBP-3 in the regulation of IGF-I-mediated cross-talk between IGF-IR and ErbB2 signaling pathways. In particular, treatment of SKBR3 cells with recombinant IGFBP-3 blocks IGF-I-induced activation of IGF-IR and ErbB2, and stable expression of IGFBP-3 inhibits SKBR3 cell growth. We find an inverse relationship in the levels of secreted IGFBP-3 such that high levels of IGFBP-3 are associated with trastuzumab-sensitive breast cancer cells (SKBR3 and BT-474), whereas low levels of IGFBP-3 are found in trastuzumab-resistant cells (clone 3 and JIMT-1). In contrast to IGFBP-3, the secretion and expression of IGFBP-2 are upregulated in trastuzumab-resistant SKBR3 cells. Furthermore, we show that IGFBP-2 stimulates activation of ErbB2 and that trastuzumab reduces IGFBP-2-stimulated ErbB2 activation. Based on our data, we propose a novel mechanism of action whereby trastuzumab enhances the expression and secretion of IGFBP-3, which interferes with IGF-I-mediated mitogenic signaling via autocrine and paracrine mechanisms and reduces IGFBP-2-induced ErbB2 activation to mediate growth inhibition. Changes in secretion profiles of IGFBP-2 and IGFBP-3 in trastuzumab-sensitive and trastuzumab-resistant cells may promote the development of IGFBP-2 and IGFBP-3 as predictive biomarkers for trastuzumab resistance.


Oral candidiasis in hematopoietic cell transplantation patients: an outcome-based analysis.
Despite aggressive antifungal prophylaxis, the increased risk for systemic fungal infection in recipients of hematopoietic cell transplants (HCT) continues to be a significant concern because Candida infection can cause morbidity and mortality in these patients. The objectives of this study were to examine the relationship of oral colonization by Candida species to systemic infection, mortality, and the impact of antifungal treatment on a population of recipients of HCT. One hundred and fifteen consecutive patients undergoing hematopoietic cell transplantation were evaluated. Oral examinations and cultures for Candida were completed before transplantation and on a weekly basis until discharge. The oral complications were assessed, and the level of mucositis was scored by using the National Cancer Institute grade. Systemic antifungal prophylaxis was provided to all patients. Chlorhexidine oral rinses were also routinely provided. Colonization by Candida species was identified in 31% of patients. Fifty-six percent of patients with colonization had clinical evidence of oral candidiasis. Significantly decreased Candida colonization was seen in patients using chlorhexidine alone compared with those using chlorhexidine and nystatin together (P <.046). Twenty-five patients died in the immediate posttransplantation period, 17 of whom were Candida-positive. The length of hospital stay ranged from 15 to 153 days; increased stay was also associated with Candida colonization (P =.04). Seventy-four percent of all patients developed ulcerative mucositis. More severe mucositis was seen in patients undergoing chemotherapy and radiation therapy. There was no significant difference between Candida colonization and the presence or severity of mucositis. Despite systemic and topical antifungal prophylaxis, oropharyngeal colonization by Candida species was common in patients who had received HCT. Candidiasis was commonly present in those who did not survive the early transplant period. Of the 25 patients who died early after the transplantation, 92% had ulcerative mucositis in comparison with 70% of those who survived, reflecting the association of oral mucositis with the toxicity of HCT. There was a significant relationship among allogeneic and autologous HCT, length of stay, and colonization of Candida. In patients undergoing systemic antifungal prophylaxis, chlorhexidine rinse was statistically more effective in reducing colonization by Candida than chlorhexidine and nystatin combined (P =.046).


Condensed fraction of an atomic Bose gas induced by critical correlations.
We study the condensed fraction of a harmonically trapped atomic Bose gas at the critical point predicted by mean-field theory. The nonzero condensed fraction f(0) is induced by critical correlations which increase the transition temperature T(c) above T(c) (MF). Unlike the T(c) shift in a trapped gas, f(0) is sensitive only to the critical behavior in the quasiuniform part of the cloud near the trap center. To leading order in the interaction parameter a/λ(0), where a is the s-wave scattering length and λ(0) the thermal wavelength, we expect a universal scaling f(0) proportionally (a/λ(0))(4). We experimentally verify this scaling using a Feshbach resonance to tune a/λ(0). Further, using the local density approximation, we compare our measurements with the universal result obtained from Monte Carlo simulations for a uniform system, and find excellent quantitative agreement.


Counting the invisible: understanding the lives of young people with disabilities in Pakistan.
To understand the lives of young people with disabilities in Pakistan using a household survey. Data were collected by administering the survey to 1094 urban and rural households randomly selected from nine districts in two provinces. The survey had a roster, which captured basic demographic, anthropometric, education and labour market status information on all resident household members in the sampled households (around 9000 individuals). In addition, detailed individual-level questionnaires were administered only to those aged between 15 and 60 years. While the survey did not have an exclusive focus on issues of disability, the questions used were informative and innovative. The findings of this survey emphasise the continued marginalisation of young people with disabilities in the areas of education, employment and marriage prospects. Additionally, reflections on the research process highlight the many challenges entailed in undertaking research on disability issues. Considering the high numbers of people reporting difficulties, many of them mild but which have a considerable impact on their functioning, there is a need for better health care planning and outreach. Given the lack of knowledge about people with disabilities - their incidence and status - there is a need for more rigorous research to help develop effective interventions.


Effect of a Compressive Garment on Kinematics of Jump-Landing Tasks.
de Britto, MA, Lemos, AL, dos Santos, CS, Stefanyshyn, DJ, and Carpes, FP. Effect of a compressive garment on kinematics of jump-landing tasks. J Strength Cond Res 31(9): 2480-2488, 2017-During jump-landing tasks, knee kinematics such as excessive valgus have been linked to knee injury in females. We determine the influence of a compressive garment on knee valgus during landing. Physically active women (n = 27, mean age 23 years) performed 4 different jump-landing tasks with 2 apparel conditions (compressive garment and regular sports shorts). Kinematic data were collected to determine knee flexion and valgus angles and the maximum jump height. Results showed that the compressive garment decreased knee flexion and knee valgus range of motion, without significant changes in the maximum jump height. As a practical application, we suggest that compression could be a strategy to reduce dynamic valgus without influencing jump performance, which motivates further study of its potential for knee injury prevention.


Involvement of neuronal acceptors for dendrotoxin in its convulsive action in rat brain.
Dendrotoxin, a snake-venom polypeptide, is a potent convulsant that facilitates transmitter release apparently by inhibition of voltage-sensitive K+ channels responsible for A-currents. A biologically active 125I-iodinated derivative of this toxin was prepared and used to characterize kinetically homogeneous non-interacting high-affinity acceptors in synaptic membranes from rat cerebral cortex and hippocampus. Binding of radiolabelled toxin from Dendroaspis angusticeps to its membrane acceptor protein was inhibitable by homologous polypeptides from other mamba snakes; most importantly, their rank order of potency was identical with that for their central neurotoxicities in rats, furnishing evidence for involvement of this binding component in the convulsive symptoms observed. Beta-Bungarotoxin, a presynaptically acting neurotoxin whose action on neurotransmitter release at the neuromuscular junction and effects on brain synaptosomes are antagonized by dendrotoxin, was only able to inhibit the binding of the 125I-labelled toxin with low efficacy, although dendrotoxin apparently interacts avidly with the acceptor sites for beta-bungarotoxin. This weak interaction of beta-bungarotoxin with the acceptor was not attributable to its phospholipolytic action. Other neurotoxins and ion-channel antagonists failed to affect the binding of dendrotoxin. The findings presented here, together with recent electrophysiological data, favour the interpretation that dendrotoxin binds to a membrane protein comprising, or closely associated with, this one group of voltage-dependent K+ channels.


Comorbidity of PTSD and depression among refugee children during war conflict.
We examined the prevalence and nature of comorbid post-traumatic stress reactions and depressive symptoms, and the impact of exposure to traumatic events on both types of psychopathology, among Palestinian children during war conflict in the region. The 403 children aged 9-15 years, who lived in four refugee camps, were assessed by completing the Gaza Traumatic Events Checklist, the Child Post Traumatic Stress Reaction Index (CPTSD-RI), and the Short Mood and Feelings Questionnaire (MFQ). Children reported experiencing a wide range of traumatic events, both direct experience of violence and through the media. CPTSD-RI and MFQ scores were significantly correlated. Both CPTSD-RI and MFQ scores were independently predicted by the number of experienced traumatic events, and this association remained after adjusting for socioeconomic variables. Exposure to traumatic events strongly predicted MFQ scores while controlling for CPTSD-RI scores. In contrast, the association between traumatic events and CPTSD-RI scores, while controlling for MFQ scores, was weak. The CPTSD-RI items whose frequency was significantly associated with total MFQ scores were: sleep disturbance, somatic complaints, constricted affect, impulse control, and difficulties in concentration. However, not all remaining CPTSD-RI items were significantly associated with exposure to traumatic events, thus raising the possibility that the association between depression and PTSD was due in part to symptom overlap. Children living in war zones are at high risk of suffering from PTSD and depressive disorders. Exposure to trauma was not found to have a unique association with PTSD. The relationship between PTSD and depressive symptomatology requires further investigation.


Protective effect of Copalite surface coating on mercury release from dental amalgam following treatment with carbamide peroxide.
The effect of Copalite coating on mercury release from dental amalgam following treatment with 10%, 20%, 30% and 40% carbamide peroxide was assessed in vitro, using a cold-vapour atomic absorption Mercury Analyzer System. Eighty samples of dental amalgam were automatically mixed in a dental amalgamator and condensed into silicon embedding molds. Forty amalgam samples were coated with three uniform layers of Copalite intermediary varnish and the other 40 samples were left uncoated. The coated and non-coated amalgam samples were exposed for 24 h to 10%, 20%, 30% or 40% carbamide peroxide preparations and compared with samples exposed to phosphate buffer. In the non-coated samples a significant increase of mercury concentration in solution was found following exposure to all carbamide peroxide preparations tested. Mercury concentration was directly related to carbamide peroxide concentration. In the Copalite-coated samples, significantly lower concentrations of mercury in solution were found as compared to the non-coated samples (P < 0.01). In conclusion, exposure of amalgam restorations to 10%-40% carbamide peroxide-based bleaching agents increased the mercury release. Pre-coating of the external amalgam surfaces with Copalite significantly reduced the release of mercury.


Characterization of the daily oxytocin rhythm in primate cerebrospinal fluid.
The circadian characteristics of the daily rhythm in oxytocin (OT) concentrations in cerebrospinal fluid (CSF) were studied in the rhesus monkey. Monkeys subjected to constant light or constant dark for periods of 3 to 6 days manifested persistence of the CSF OT rhythm. A 12-hr phase shift in the light-dark cycle resulted in a resynchronization of the rhythm to the new lighting schedule within 3 to 4 days. Altering the daily feeding and care schedule during a period of constant darkness did not alter the expression or timing of the CSF OT rhythm significantly. These results suggest that the OT rhythm is endogenously generated and that the daily light-dark cycle normally synchronizes the rhythm to the 24-hr cycle.