Induction of lesions of selenium-vitamin E deficiency in ducklings fed silver, copper, cobalt, tellurium, cadmium, or zinc: protection by selenium or vitamin E supplements.
In 3 experiments, 684 newly hatched White Pekin ducklings were fed (for 15 to 28 days) a commercial starter mash that was adequate in selenium and vitamin E (Se-E) content, either alone or with supplements of Ag (3,000 mg/kg of feed, as acetate), Cu (1,500 mg/kg, as sulfate), Co (200 or 500 mg/kg, as chloride), Te (500 mg/kg, as tetrachloride), Cd (100 or 500 mg/kg, as sulfate), Zn (3,000 or 6,000 mg/kg, as sulfate), or V (100 mg/kg, as vanadate). The ducklings fed Ag, Cu, Co, Te, Cd, and Zn frequently developed lesions characteristic of Se-E deficiency, such as necrosis of skeletal and cardiac muscle and of smooth muscle of the gizzard and intestine. Complete protection from the muscle lesions produced by Cu, Co, Te, Cd, and Zn supplements was provided by vitamin E (200 IU of alpha-tocopherol acetate/kg) and Se (2 mg/kg, as selenite). Ducklings fed Ag were protected by supplements of vitamin E and partial protection was achieved by Se addition. The birds fed excessive Zn developed pancreatic necrosis and fibrosis that was not prevented by supplements of Se or vitamin E. Terminally, blood glutathione peroxidase activity was low and hepatic Se concentration was increased in the ducklings fed Ag. However, neither blood glutathione peroxidase activity nor hepatic Se concentrations was consistently abnormal in ducklings fed other trace elements, although lesions of Se-E deficiency were often present in these animals.


Renal and cardiac function during alpha1-beta-blockade in congestive heart failure.
The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function. Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol. Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR). but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol. Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.


When birds can't fly: an analysis of interfacility ground transport using advanced life support when helicopter emergency medical service is unavailable.
Helicopter emergency medical service (HEMS) transport of trauma patients is costly and of unproven benefit. Recent retrospective studies fail to control for crew expertise and therefore compare highly trained advance life support with less-trained basic life support crews. The purpose of our study was to compare HEMS with ground, interfacility transport while controlling for crew training. We hypothesized that patients transported by HEMS would experience shorter interhospital transport time and reduced mortality. Our National Trauma Registry of the American College of Surgeons database was retrospectively queried to identify consecutive interfacility, hospital transfers (January 1, 2008, to November 1, 2012) to our Level I trauma center. Transfers were stratified by transportation vehicle (i.e., HEMS vs. ground transport). Cohorts were compared across standard demographic and clinical variables using univariate analysis. Multivariate logistic regression was performed to determine the association of these variables with mortality. The HEMS (n = 2,190) and ground (n = 223) cohorts were well matched overall, with no significant differences for demographics, injury severity, physiology, hospital length of stay, or complications. Median (interquartile range) time to definitive care was significantly lower for HEMS (150 [114] minutes vs. 255 [157] minutes, p < 0.001), without change in mortality (9.0% vs. 8.1%, p = 0.71). Multivariate logistic regression did not identify an association between transport mode and mortality. Despite faster interfacility transport times, HEMS offered no mortality benefit compared with ground when crew expertise was controlled for, contradicting recent large, retrospective National Trauma Data Bank studies. Our study may represent the best approximation of a prospective study by focusing on patients deemed worthy of HEMS by referring providers. Although HEMS may seem intuitively beneficial for time-dependent injuries, larger studies with a similar methodology are warranted to justify the cost and risk of HEMS and identify subsets of patients who may benefit. Prognostic/epidemiologic study, level III.


Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.
The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.


Effects of Mg2+, anions and cations on the Ca2+ + Mg2+-activated ATPase of sarcoplasmic reticulum.
In a previous paper [Gould, East, Froud, McWhirter, Stefanova & Lee (1986) Biochem. J. 237, 217-227] we presented a kinetic model for the activity of the Ca2+ + Mg2+-activated ATPase of sarcoplasmic reticulum. Here we extend the model to account for the effects on ATPase activity of Mg2+, cations and anions. We find that Mg2+ concentrations in the millimolar range inhibit ATPase activity, which we attribute to competition between Mg2+ and MgATP for binding to the nucleotide-binding site on the E1 and E2 conformations of the ATPase and on the phosphorylated forms of the ATPase. Competition is also suggested between Mg2+ and MgADP for binding to the phosphorylated form of the ATPase. ATPase activity is increased by low concentrations of K+, Na+ and NH4+, but inhibited by higher concentrations. It is proposed that these effects follow from an increase in the rate of dephosphorylation but a decrease in the rate of the conformational transition E1'PCa2-E2'PCa2 with increasing cation concentration. Li+ and choline+ decrease ATPase activity. Anions also decrease ATPase activity, the effects of I- and SCN- being more marked than that of Cl-. These effects are attributed to binding at the nucleotide-binding site, with a decrease in binding affinity and an increase in 'off' rate constant for the nucleotide.


Lentiviruses allow widespread and conditional manipulation of gene expression in the developing mouse brain.
Generation of transgenic mice, in utero electroporation and viral injection are common approaches to manipulate gene expression during embryonic development of the mammalian brain. While very powerful in many contexts, these approaches are each characterized by their own limitations: namely, that generation of transgenic mice is time-consuming and electroporation only allows the targeting of a small area of the brain. Similarly, viral injection has been predominantly characterized by using retroviruses or adenoviruses that are limited by a relatively low infectivity or lack of integration, respectively. Here we report the use of integrating lentiviral vectors as a system to achieve widespread and efficient infection of the whole brain after in utero injection in the telencephalic ventricle of mouse embryos. In addition, we explored the use of Cre-mediated recombination of loxP-containing lentiviral vectors to achieve spatial and temporal control of gene expression of virtually any transgene without the need for generation of additional mouse lines. Our work provides a system to overcome the limitations of retroviruses and adenoviruses by achieving widespread and high efficiency of transduction. The combination of lentiviral injection and site-specific recombination offers a fast and efficient alternative to complement and diversify the current methodologies to acutely manipulate gene expression in developing mammalian embryos.


Thoracic Endometriosis Syndrome: A Review of Diagnosis and Management.
Endometriosis is characterized by the presence of endometrial-like glands and stroma outside the uterine cavity and is believed to affect 6%-10% of reproductive-age women. Endometriosis within the lung parenchyma or on the diaphragm and pleural surfaces produces a range of clinical and radiological manifestations. This includes catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules, resulting in an entity known as thoracic endometriosis syndrome (TES). Computerized searches of MEDLINE and PubMed were conducted using the key words "thoracic endometriosis," "catamenial pneumothorax," "catamenial hemothorax," and "catamenial hemoptysis." References from identified sources were manually searched to allow for a thorough review. TES can produce incapacitating symptoms for some patients. Symptoms of TES are nonspecific, so a high degree of clinical suspicion is warranted. Medical management represents the first-line treatment approach. When this fails or is contraindicated, definitive surgical treatment for cases of suspected TES uses a combined video laparoscopy performed by a gynecologic surgeon and video-assisted thoracoscopic surgery performed by a thoracic surgeon. Postoperative hormonal suppression may further reduce disease recurrence.


Transgastric surgery for posterior juxtacardial ulcers: a minimal and safe approach.
A transgastric approach may be used succesfully for the treatment of posterior juxtacardial ulcers presenting with massive bleeding. Eight patients were admitted during a 6-year period with acute massive upper gastrointestinal bleeding caused by posterior juxtacardial ulcers. All patients had signs of profound hypovolemic shock, and initial endoscopic control was achieved in 3 patients. They all underwent surgery after endoscopy. At operation, the ulcer was approached through an anteromedial gastrostomy and hemostasis was achieved by transfixing stitches. Ulcers were excised whenever possible, or excluded if adherent posteriorly. Four-quadrant biopsy was taken for frozen section to exclude malignancy. Both anterior and posterior gastric walls were then closed with nonabsorbable suture material. There were 6 men and 2 women with a mean age of 73 years. Hemoglobin levels ranged from 5.2 to 8.0 g/dL. Five patients underwent emergency surgery within 28 hours of admission. The diameter of the ulcers ranged from 2 to 5 cm. Ulcerectomy was performed in 6 cases. In the remaining 2 patients, the crater of the ulcer was adherent to the diaphragm and required exclusion from the gastrointestinal tract. None of the ulcers proved to be malignant, and there were no operative deaths. Patients were followed up for a mean of 3 years with no complications. Satisfactory results can be achieved with a transgastric approach to these rare ulcers. This allows definitive treatment while avoiding major gastric resection with its potential complications.


Role of natural killer cells in a cohort of elite suppressors: low frequency of the protective KIR3DS1 allele and limited inhibition of human immunodeficiency virus type 1 replication in vitro.
Natural killer (NK) cells are associated with the innate immune response and are important in many viral infections. Recent studies indicate that NK cells can control human immunodeficiency virus type 1 (HIV-1) replication. We studied the effect of NK cells on HIV-1 replication in a subpopulation of HIV-1-infected individuals termed elite suppressors (ES) or elite controllers. These patients maintain a clinically undetectable viral load without treatment and thus provide a fascinating cohort in which to study the immunological response to HIV-1. Using an autologous system, we analyzed the effects of NK cells and CD8(+) T cells on viral replication in CD4(+) T lymphoblasts. Although we had postulated that NK cells of ES would be highly effective at controlling viral replication, we found that NK cells from some, but not all, ES were capable of inhibiting replication in the presence of interleukin-2, and the inhibition was less robust than that mediated by CD8(+) T cells. Additionally, we examined whether particular alleles of the KIR receptors, specifically KIR3DS1 and KIR3DL1, or allele-ligand combinations correlated with the control of HIV-1 replication by NK cells and whether any specific KIR alleles were overrepresented in ES. Our ES cohort did not differ from the general population with respect to the frequency of individual KIR. However, of the eight ES studied, the four exhibiting the most NK cell-mediated control of viral replication also had the fewest activating KIR and were haplotype A. Thus, the strong NK cell-mediated inhibition of viral replication is not necessary for the immunological control of HIV-1 in all ES.


Mycophenolic acid in diabetic renal transplant recipients: pharmacokinetics and application of a limited sampling strategy.
Limited sampling strategies may be useful in optimizing therapeutic drug monitoring of mycophenolic acid (MPA). Their use, however, may be limited by several patient factors, including comorbidity. In this study the pharmacokinetics of MPA in diabetic and nondiabetic renal transplant recipients were compared, and it was evaluated whether a limited sampling strategy developed and validated for nondiabetic patients can also be used in diabetic patients. The pharmacokinetics of MPA were analyzed on days 7 and 11 after transplantation in 136 renal transplant patients, among whom 7 patients had diabetes. All patients received cyclosporine and corticosteroids as maintenance immunosuppressive therapy. A limited sampling strategy [AUC (mg x h/L) = 7.182 + 4.607 C0 + 0.998 C0.67 + 2.149 C2] was developed and validated for nondiabetic patients and was subsequently tested for its usefulness in diabetic patients. Diabetic renal transplant patients did not have significantly different dose-normalized MPA area under concentration-time curve (AUC), MPA clearance, or MPA maximum concentration (Cmax). However, in diabetic patients Tmax (time of Cmax, 1.59 hours) was higher than for nondiabetic patients (0.67 hours) on day 11 (P = 0.04). The developed and validated limited sampling strategy performed acceptably, estimating MPA AUC in nondiabetic patients with a mean bias of 0.2 mg x h/L (95% confidence interval from -1.3 to 1.6 mg x h/L). Applying the limited sampling strategy in diabetic patients revealed a mean bias of -1.5 (-5.7, 2.7 mg x h/L). In conclusion, although diabetic renal transplant patients exhibit increased Tmax, this does not affect the accuracy of the limited sampling strategy.


HLA genotyping in pediatric celiac disease patients.
Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 90-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children's Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1*02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development.


Total synthesis and cloning of a gene coding for the ribonuclease S protein.
A gene for ribonuclease S protein, has been chemically synthesized and cloned. The gene is designed to have 25 specific restriction endonuclease sites spaced at short intervals, permitting its structure to be rapidly modified. This flexibility facilitates tests of hypotheses relating the primary structure of the enzyme to its physical and catalytic behavior.


A higher significance of anaerobes: the clone library analysis of bacterial pleurisy.
The frequencies of etiologic bacterial agents of intrapleural infections reported until now have been widely varied, largely depending on the implemented detective methods. The aims of this study were to evaluate bacterial etiologies of bacterial pleurisy using a cultivation-independent method. Pleural fluids were collected from 42 febrile patients with hemipleural effusion. The bacterial flora was analyzed by a clone library method using amplified fragments of the 16S ribosomal RNA gene (rDNA) with universal primers in addition to conventional cultivation methods. Forty-two specimens were obtained from 26 patients with bacterial pleurisy, seven with mycobacterial pleurisy, and nine with other pleural effusions. In the 26 bacterial cases, 16 (61.5%) showed positive results for 16S rDNA sequencing analysis, of which 11 (42.3%) were also positive for cultivation method. In seven (43.8%) of the 16 polymerase chain reaction-positive cases, anaerobic phylotypes were predominantly detected. Anaerobic phylotypes (six of these seven cases) were not detected by cultivation method. In nine (34.6%) of the 26 bacterial pleural cases, the results from the clone library methods were not accordant with those of the cultivation method. In seven of these nine cases, the discrepancies between the two detection methods were due to the existence of anaerobes. The clone library analysis using the 16S rDNA of pleural fluid showed a higher incidence of anaerobic bacteria in infectious pleurisy than that previously expected and provided additional bacterial information for cultivation methods.


Left ventricular hypertrophy is associated with arterial stiffness and vascular calcification in hemodialysis patients.
Left ventricular hypertrophy (LVH) is the most frequent cardiac abnormality in patients with end-stage renal disease (ESRD). Recent studies have shown that arterial stiffness is associated with mediacalcinosis in these patients. However, whether arterial stiffness and vascular calcification are associated with the LVH in patients with ESRD has not been well established. Forty-nine patients on chronic hemodialysis participated in this study. 1) To better understand the mechanism underlying the increased incidence of LVH, we studied the relation between LVH and each of arterial wall stiffness, aortic calcification, and numerous clinical parameters in 49 patients on chronic hemodialysis. 2) To evaluate the contribution of arterial stiffness and arterial calcification to LVH in hemodialysis patients, we performed the present clinical analysis on 49 patients on chronic hemodialysis. We used an automatic device to measure arterial pulse wave velocity (PWV) as an index of arterial wall stiffness. The aortic calcification index (ACI) was quantified morphometrically by CT scan. The left ventricular mass index (LVMI) was estimated by M-mode echocardiography. To understand the mechanism underlying the increased incidence of LVH, we examined the factors contributing to LVMI in these patients. The correlation between each of the study parameters and LVMI as an indicator of LVH was then examined. The LVMI value was correlated positively with PWV (r=0.439, p=0.0014), systolic blood pressure (r=0.421, p=0.0023), and ACI (r=0.467, p=0.0006). A stepwise linear regression analysis showed that PWV, systolic blood pressure, and ACI were independently associated with LVH in our subjects. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients, with vascular calcification being the most important contributor to the development of LVH. Alteration of pulsatile dynamics contributes to an increase in left ventricular load and thus is also related to the LVH in these patients. These results suggest that LVH is associated with hypertension, increased arterial stiffness, and the extent of vascular calcification in hemodialysis patients. Vascular calcification, which alters the pulsatile dynamics and thereby contributes to an increase in left ventricular load, is the most important contributor to the development of LVH in patients undergoing hemodialysis.


Discrimination and identification of vowels by young, hearing-impaired adults.
This study examined the effects of mild-to-moderate sensorineural hearing loss on vowel perception abilities of young, hearing-impaired (YHI) adults. Stimuli were presented at a low conversational level with a flat frequency response (approximately 60 dB SPL), and in two gain conditions: (a) high level gain with a flat frequency response (95 dB SPL), and (b) frequency-specific gain shaped according to each listener's hearing loss (designed to simulate the frequency response provided by a linear hearing aid to an input signal of 60 dB SPL). Listeners discriminated changes in the vowels /I e E inverted-v ae/ when F1 or F2 varied, and later categorized the vowels. YHI listeners performed better in the two gain conditions than in the conversational level condition. Performances in the two gain conditions were similar, suggesting that upward spread of masking was not seen at these signal levels for these tasks. Results were compared with those from a group of elderly, hearing-impaired (EHI) listeners, reported in Coughlin, Kewley-Port, and Humes [J. Acoust. Soc. Am. 104, 3597-3607 (1998)]. Comparisons revealed no significant differences between the EHI and YHI groups, suggesting that hearing impairment, not age, is the primary contributor to decreased vowel perception in these listeners.


Phosphoglycerides of Trichophyton terrestre and one phenotype selected from the Apollo 16 microbial ecology evaluation device.
Total lipid extracted from wild-type Trichophyton terrestre CDC-X285 was found to be 2.0 percent of the dry cell weight. The total lipid contained the following phospholipid components identified by silicic acid-impregnated thin-layer and paper chromatography: phosphatidyl inositol, phosphatidyl choline, phosphatidyl serine, and phosphatidic acid. The total lipid extracted from the phenotype T. terrestre 7048-1 isolated from the Apollo 16 Microbial Ecology Evaluation Device (MEED) was found to vary according to the time at which the phospholipids were extracted. The Trichophyton phenotype was selected from a cuvette housed in the MEED exposed to specific space parameters including ultraviolet light of known wavelengths and energy levels in deep space. The phospholipid components, identified in the phenotype were phosphatidyl ethanolamine and cardiolipin. The major lipid fraction was composed of digalactosyl diglyceride and monogalactosyl diglyceride. An unusual lipid was detected in the phenotype, which appeared to be sterol glycoside.


Superoxide assay-leukocyte adherence inhibition test and a soluble factor which stimulates the adherence of macrophages.
A modified method for the leukocyte adherence inhibition test is described. Peritoneal cells from immune guinea pigs or peripheral mononuclear cells from cancer patients were incubated with immunizing antigen or tumor extract in a 4-mm-wide glass microcell for spectrophotometer analysis. Instead of visual cell counting, the cells adherent to the bottom of the microcell were stimulated with cytochalasin E and wheat germ agglutinin, and the amount of the superoxide (O2.-) generated from the adherent macrophages or monocytes was assayed. Antigen-specific adherence inhibition of peritoneal cells of the immunized guinea pigs was detected 2 weeks after immunization. In contrast, cell adherence was stimulated after 3 weeks. It was shown that a soluble factor was responsible for the adherence stimulation and that nonadherent cells were necessary for its production. Peripheral mononuclear cells of 70% of the tumor-bearing lung cancer patients reacted to the lung tumor extract (9 adherence inhibitions and 7 adherence stimulations per 23 patients). Twenty-five % (3 of 12) of tumor-free patients showed positive reactions, all with adherence stimulation. Of the 12 healthy donors, 3 cases of pneumonia, one case of angiosarcoma of the left flank, one case of hemangiopericytoma of the mediastinum, and 8 cases of breast cancer, non reacted with the lung tumor extract, and only one of 7 lung tuberculosis patients showed positive adherence stimulation.


Systemic vitamin D supplementation and local bone formation after maxillary sinus augmentation - a randomized, double-blind, placebo-controlled clinical investigation.
Maxillary sinus augmentation procedures with bone replacement grafts aimed to increase bone height in the posterior maxilla. During healing, bone particles are partially resorbed and replaced by the patient's own bone. Vitamin D plays an essential role in calcium homeostasis and is critical for bone formation and remodeling. This randomized, double-blind, placebo-controlled clinical investigation studied whether oral supplementation with vitamin D3 (5000 IU) combined with calcium (600 mg) impacts bone formation and remodeling after maxillary sinus augmentation compared to a placebo medication containing calcium alone (n = 10/group). Bone cores were harvested at the time of implant placement (6-8 months) for histological analysis. Serum 25-hydroxyvitamin D (25-OHD) levels were comparable between both groups at the baseline (P = nonsignificant [n.s.]). Vitamin D3+ calcium supplementation improved significantly serum 25-OHD levels (placebo vs. vitamin D3 group: 25-OHD ng/ml: 31.13 ± 7.06 vs. 61.11 ± 20.42, P ≤ 0.01); however, no statistically significant difference in bone formation or graft resorption was detected between groups. However, in the vitamin D3 group, a significant association was found between increased vitamin D levels and number of bone-resorbing osteoclasts around graft particles suggesting that local bone remodeling might be more pronounced when serum vitamin D levels were improved (r = 0.92, P ≤ 0.05). Vitamin D3+ calcium supplementation improves serum vitamin D levels and potentially impacts local bone remodeling on a cellular level. However, no statistically significant difference in bone formation or graft resorption was detected between groups.


Single gene-mediated shift in pollinator attraction in Petunia.
Animal-mediated pollination is essential in plant reproductive biology and is often associated with pollination syndromes, sets of floral traits, such as color, scent, shape, or nectar content. Selection by pollinators is often considered a key factor in floral evolution and plant speciation. Our aim is the identification and characterization of the genetic changes that caused the evolution of divergent pollination syndromes in closely related plant species. We focus on ANTHOCYANIN2 (AN2), a well-defined myb-type transcription factor that is a major determinant of flower color variation between Petunia integrifolia and Petunia axillaris. Analysis of sequence variation in AN2 in wild P. axillaris accessions showed that loss-of-function alleles arose at least five times independently. DNA sequence analysis was complemented by functional assays for pollinator preference using genetic introgressions and transgenics. These results show that AN2 is a major determinant of pollinator attraction. Therefore, changes in a single gene cause a major shift in pollination biology and support the notion that the adaptation of a flowering plant to a new pollinator type may involve a limited number of genes of large effect. Gene identification and analysis of molecular evolution in combination with behavioral and ecological studies can ultimately unravel the evolutionary genetics of pollination syndromes.


International inter-rater agreement in scoring acne severity utilizing cloud-based image sharing of mobile phone photographs.
Cloud-based image sharing technology allows facilitated sharing of images. Cloud-based image sharing technology has not been well-studied for acne assessments or treatment preferences, among international evaluators. We evaluated inter-rater variability of acne grading and treatment recommendations among an international group of dermatologists that assessed photographs. This is a prospective, single visit photographic study to assess inter-rater agreement of acne photographs shared through an integrated mobile device, cloud-based, and HIPAA-compliant platform. Inter-rater agreements for global acne assessment and acne lesion counts were evaluated by the Kendall's coefficient of concordance while correlations between treatment recommendations and acne severity were calculated by Spearman's rank correlation coefficient. There was good agreement for the evaluation of inflammatory lesions (KCC = 0.62, P < 0.0001), noninflammatory lesions (KCC = 0.62, P < 0.0001), and the global acne grading system score (KCC = 0.69, P < 0.0001). Topical retinoid, oral antibiotic, and isotretinoin treatment preferences correlated with photographic based acne severity. Our study supports the use of mobile phone based photography and cloud-based image sharing for acne assessment. Cloud-based sharing may facilitate acne care and research among international collaborators.


High Sensitivity, Wide Linear-Range Strain Sensor Based on MXene/AgNW Composite Film with Hierarchical Microcrack.
Stretchable strain sensors suffer the trade-off between sensitivity and linear sensing range. Developing sensors with both high sensitivity and wide linear range remains a formidable challenge. Different from conventional methods that rely on the structure design of sensing nanomaterial or substrate, here a heterogeneous-surface strategy for silver nanowires (AgNWs) and MXene is proposed to construct a hierarchical microcrack (HMC) strain sensor. The heterogeneous surface with distinct differences in cracks and adhesion strengths divides the sensor into two regions. One region contributes to high sensitivity through penetrating microcracks of the AgNW/MXene composite film during stretching. The other region maintains conductive percolation pathways to provide a wide linear sensing range through network microcracks. As a result, the HMC sensor exhibits ultrahigh sensitivity (gauge factor ≈ 244), broad linear range (ɛ = 60%, R2 ≈ 99.25%), and fast response time (<30 ms). These merits are confirmed in the detection of large and subtle human motions and digital joint movement for Morse coding. The manipulation of cracks on the heterogeneous surface provides a new paradigm for designing high-performance stretchable strain sensors.


Health-effects related structure-toxicity relationships: a paradigm for the first decade of the new millennium.
Prediction of the effects of industrial chemicals to humans will be an area of increasing concern in the next century. The role of quantitative structure-activity relationships (QSARs) is to aid in the prediction of effects by determination of the limits of variation in structure that are consistent with the production of a specific toxic effect and define the ways in which alterations in structure influences toxicity. The paradigm followed in the development of QSARs for ecotoxic-endpoints has been successful as a direct result of the availability of in vivo toxicity data in which to build initial QSARs and validate surrogate test systems. However, the lack of quantitative in vivo toxicity data means this paradigm cannot be used in the prediction of human health-effect endpoints. Therefore, a new paradigm, which provides guidance in the use of predictive QSARs for health-effects that serves to circumvent the problems associated with the lack of whole-mammal toxicity data must be established. A scenario is given that provides for the development, standardization, and validation of health-effects related QSARs in the first decade of the 21st century. Due to the structural diversity and sheer number of industrial organic chemicals, assays used to garner health-effects data must be based on quantifiable, rapid, reliable, and inexpensive surrogate endpoints. New 'biotools' developed using modern molecular techniques will aid in the circumvention of in vivo health-effects data and provide measurable endpoints, which can be used as surrogates for health-effects endpoints. This has particular application in receptor-mediated toxicity and gene expression. The lack of whole-mammal health-effects data means that the standardization and validation, of these endpoints will be accomplished in novel ways. Databases garnered using modern biotools will allow the derivation of QSARs developed for validated surrogate health-effect endpoints. If QSARs are to be useful in bridging gaps in health-effects data, they must be based on accurate, reproducible data for a robust series of non-congeneric chemicals. The latter applies to both toxicity and descriptor values. Because health-effects are often the result of metabolic activation, if these new QSARs are to be meaningful, validated software for predicting metabolite formation must be incorporated. Lastly, once QSARs and software are developed and validated, they will need to be linked into some type of expert system.


Brief report: A pilot study of a web-based resource for families of children with cancer.
To develop a Web-based resource for families of children newly diagnosed with cancer and examine the viability of this modality of providing support. Twenty-one children (8-17 years) newly diagnosed with cancer and their families were enrolled. Quantitative data on Web site utilization and frequency of accessing specific sections and qualitative data on participant satisfaction are reported. Twenty-one families comprising 51 participants (children with cancer, parents, and siblings) had access to the Web site. Utilization was lower than anticipated, with members of only nine families accessing the site. The majority of these hits were on peer discussion groups. Further research is warranted to examine whether the Internet is a viable method of delivering support to families affected by childhood cancer. The current pattern of results suggests that the timing of its introduction and the method used to train families may affect utilization.


Age is not a significant risk factor for failed trial of beta-blocker therapy in older patients with chronic heart failure.
To evaluate how well older heart failure patients tolerate beta-blockers in everyday clinical practice. Retrospective casenote analysis. Specialist heart failure clinic in a large teaching hospital. 226 patients with a clinical diagnosis of heart failure and evidence of left ventricular systolic dysfunction. Data on age, sex, comorbid illness, other medications, duration of beta-blocker therapy, side-effects and reasons for discontinuation. Patients aged 75 years and over had a higher level of comorbid disease and worse New York Heart Association status. Despite this, 60.4% of those aged 75 or over had been tried on a beta-blocker (versus 69% of those aged <75), and of those tried, 80% of those aged 75 or over were still taking a beta-blocker at the time of survey (versus 86% of those aged <75). Forty-seven percent of those aged 75 or over had at least one side-effect recorded (versus 48% of those aged <75). Significant risk factors for failing a trial of beta-blocker therapy were worse New York Heart Association status and worse left ventricular function, but importantly not age. A high proportion of older heart failure patients tolerate beta-blockers. Side-effects and failure rates are comparable to younger patients. Left ventricular function and worse New York Heart Association class, rather than age, predict low tolerability of therapy. Further studies are warranted to evaluate whether frail patients with heart failure can improve their quality of life by taking beta-blockers.


Factors Influencing the Adequacy of Bowel Preparation in Patients With Developmental Disabilities.
The rate of inadequate bowel preparation in the general population is approximately 23%. As more individuals with developmental disabilities enter late adulthood, a concomitant rise in endoscopic procedures for this population, including screening colonoscopies, is anticipated. However, there are sparse data on the adequacy of bowel preparation in patients with developmental disabilities. A retrospective analysis of 91 patients with developmental disabilities who underwent colonoscopy from 2006 to 2014 was performed. Bowel preparation adequacy from these procedures was evaluated, together with other data, including age, developmental disability diagnoses, procedure type, indication and setting. Mean age at the time of endoscopy was 52.6 ± 13.4 years, with an age range of 18 - 74 years. Inadequate bowel preparation was found in approximately 51% of documented cases. Outpatients were more likely to have adequate bowel preparation compared to inpatients, with an odds ratio of 2.75 (95% confidence interval: 1.14 - 6.62, P = 0.022). No other major factors identified had any statistically significant influence on the adequacy of bowel preparation. Over half of patients with developmental disabilities undergoing colonoscopy had inadequate bowel preparations in our study, which is more than twice the rate for the general population. Furthermore, outpatients were 2.75 times more likely to have adequate bowel preparation compared to inpatients. Further studies are recommended to improve endoscopic practices for this patient population.


Effect of primary tumour resection without curative intent in patients with metastatic neuroendocrine tumours of the small intestine and right colon: meta-analysis.
Patients with small intestinal neuroendocrine tumours (siNETs) usually present with advanced disease. Primary tumour resection without curative intent is controversial in patients with metastatic siNETs. The aim of this meta-analysis was to investigate survival after primary tumour resection without curative intent compared with no resection in patients with metastatic siNETs. A systematic literature search was performed, using MEDLINE® (PubMed), Embase®, Web of Science, and the Cochrane Library up to 25 February 2021. Studies were included if survival after primary tumour resection versus no resection in patients with metastatic siNETs was reported. Results were pooled in a random-effects meta-analysis, and are reported as hazard ratios (HRs) with 95 per cent confidence intervals. Sensitivity analyses were undertaken to enable comment on the impact of important confounders. After screening 3659 abstracts, 16 studies, published between 1992 and 2021, met the inclusion criteria, with a total of 9428 patients. Thirteen studies reported HRs adjusted for important confounders and were included in the meta-analysis. Median overall survival was 112 (i.q.r. 82-134) months in the primary tumour resection group compared with 60 (74-88) months in the group without resection. Five-year overall survival rates were 74 (i.q.r. 67-77) and 44 (34-45) per cent respectively. Primary tumour resection was associated with improved survival compared with no resection (HR 0.55, 95 per cent c.i. 0.47 to 0.66). This effect remained in sensitivity analyses. Primary tumour resection is associated with increased survival in patients with advanced, metastatic siNETs, even after adjusting for important confounders.


Refined HLA-DPB1 mismatch with molecular algorithms predicts outcomes in hematopoietic stem cell transplantation.
HLA-DPB1 mismatches between donor and recipient are commonly seen in allogeneic hematopoietic stem cell transplantation from an unrelated donor. HLA-DPB1 mismatch, conventionally determined by the similarity of the T-cell epitope (TCE), is associated with an increased risk of acute graft-versus-host disease (GVHD) and a decreased risk of disease relapse. We investigated the clinical impact of HLA-DPB1 molecular mismatch quantified by mismatched eplets (ME) and the Predicted Indirectly Recognizable HLA Epitopes Score (PS) in a cohort of 1,514 patients receiving hematopoietic stem cell transplants from unrelated donors matched at HLA-A, -B, -C, -DRB1/3/4/5, and - DQB1 loci. HLA-DPB1 alloimmunity in the graft-versus-host direction, determined by high graft-versus-host ME/PS, was associated with a reduced risk of relapse (hazard ratio [HR]=0.83, P=0.05 for ME) and increased risk of grade 2-4 acute GVHD (HR=1.44, P<0.001 for ME), whereas high host-versus-graft ME/PS was only associated with an increased risk of grade 2-4 acute GVHD (HR=1.26, P=0.004 for ME). Notably, in the permissive mismatch subgroup classified by TCE grouping, high host-versus-graft ME/PS was associated with an increased risk of relapse (HR=1.36, P=0.026 for ME) and grade 2-4 acute GVHD (HR=1.43, P=0.003 for PS-II). Decision curve analysis showed that graftversus- host ME outperformed other models and provided the best clinical net benefit for the modification of acute GVHD prophylaxis regimens in patients with a high risk of developing clinically significant acute GVHD. In conclusion, molecular assessment of HLA-DPB1 mismatch enables separate prediction of host-versus-graft or graft-versus-host alloresponse quantitatively and allows further refinement of HLA-DPB1 permissiveness as defined by conventional TCE grouping.


Terahertz near-field microscopy of complementary planar metamaterials: Babinet's principle.
Using terahertz near-field imaging we experimentally investigate the resonant electromagnetic field distributions behind a split-ring resonator and its complementary structure with sub-wavelength spatial resolution. For the out-of-plane components we experimentally verify complementarity of electric and magnetic fields as predicted by Babinet's principle. This duality of near-fields can be used to indirectly map resonant magnetic fields close to metallic microstructures by measuring the electric fields close to their complementary analogues which is particularly useful since magnetic near-fields are still extremely difficult to access in the THz regime. We find excellent agreement between the results from theory, simulation and two different experimental near-field techniques.


Next-generation high-density self-assembling functional protein arrays.
We developed a high-density self-assembling protein microarray, based on the nucleic acid programmable protein array (NAPPA) concept, to display thousands of proteins that are produced and captured in situ from immobilized cDNA templates. We arrayed up to 1,000 unique human cDNAs and obtained high yields of protein expression and capture with minimal variation and good reproducibility. This method will enable various experimental approaches to study protein function in high throughput.


How much do locked screws add to the fixation of "hybrid" plate constructs in osteoporotic bone?
Hybrid locked plating has become a commonly used technique for treating complex fractures and nonunions, but information is lacking to direct the specific application of this fixation method. The purpose of this study was to determine the effect of the number and location of locked screws on the mechanical properties of hybrid plate constructs in an osteoporotic bone model. A synthetic commercial composite model of osteoporotic bone with a 5-mm simulated fracture gap was fixed with a 12-hole plate. Seven different constructs (n=5/construct) were tested including 2 unlocked and 5 hybrid configurations. All constructs used bicortical screws tightened to 4 N.m torque. Cyclic (sinusoidal) testing was performed with a peak torsional load of +/-8 N.m for 100,000 cycles. Torsional stiffness of each construct was measured in 10,000 cycle increments, and the maximum removal torque of each screw was measured at the conclusion of torsional testing. Stiffness of the constructs at each testing interval was most affected by the number of screws; stiffness increased at least 33% when 4 screws were used on each side of the fracture versus 3 per side. Among the constructs with 4 screws in each fragment, no difference was observed when 1 or 2 unlocked screws were replaced with locked screws on each side of the simulated fracture. In contrast, replacement of 3 unlocked screws with locked screws increased the torsional stiffness of the construct by another 24% (P<0.001). Compared with baseline (pretesting) values, postcycling screw removal torque was similar for locked screws at all positions (average 50% of peak removal), but removal torque of unlocked screws furthest from the fracture was increased by 274% if they were placed immediately adjacent to a locked screw (P<0.001). At least 3 bicortical locked screws on each side of a fracture are needed to increase the torsional stiffness in an osteoporotic bone model. Locked screws placed between the fracture and unlocked screws protect the unlocked screws from loosening and may have some clinical utility in improving fatigue life of the construct. Biomechanical level 1.


Contact urticaria to O-phenylphenate.
Contact urticaria is a form of immediate hypersensitivity reaction that is being noted with increasing frequency. This report illustrates an unusual presentation of contact urticaria in the form of an immediate reaction to a component of plaster cast material. The substance involved was ortho-phenylphenate, a preservative. It has not been previously implicated in a contact urticaria reaction.


A prospective multicenter study of the effect of patient education on acceptability of generic prescribing in general practice.
The purpose of the study was to assess patients' acceptability of the substitution of brand-name drugs for generic drugs in the primary health care prescribing practices for chronic conditions. A prospective randomised multicentre study was conducted over a 12-month period in which patients taking medications for chronic disorders received an educational intervention on generic drugs at the time they attended different general practices in the city of Barcelona (Spain) for repeat prescribing. Twenty-seven public primary care centres were randomised to the intervention group (eight centres) or the control group (19 centres). Of 4620 patients in the intervention group that received verbal information and handout materials on advantages and disadvantages of generic equivalents and brand-name drugs, 98.9% of them agreed to receive a generic formulation. The primary care centre and the class of drug were associated with statistically significant differences in the percentage of acceptance of generic drugs. In the overall population, generic prescribing in the intervention practices increased to 5.9 as compared with 2.8% in controls. In summary, individual educational intervention in patients with repeat prescribing resulted in a high rate of generic acceptability. The intervention might stimulate the practitioner's motivation, behaviour and knowledge of generic forms.


Theoretical investigation of electronic excitation energy transfer in bichromophoric assemblies.
Electronic excitation energy transfer (EET) rates in rylene diimide dyads are calculated using second-order approximate coupled-cluster theory and time-dependent density functional theory. We investigate the dependence of the EET rates on the interchromophoric distance and the relative orientation and show that Forster theory works quantitatively only for donor-acceptor separations larger than roughly 5 nm. For smaller distances the EET rates are over- or underestimated by Forster theory depending on the respective orientation of the transition dipole moments of the chromophores. In addition to the direct transfer rates we consider bridge-mediated transfer originating from oligophenylene units placed between the chromophores. We find that the polarizability of the bridge significantly enhances the effective interaction. We compare our calculations to single molecule experiments on two types of dyads and find reasonable agreement between theory and experiment.


"Anonymous Meltdown": Content Themes Emerging in a Nonfacilitated, Peer-only, Unstructured, Asynchronous Online Support Group for Family Caregivers.
By providing care for loved ones in the home, family caregivers save millions of dollars for our overtaxed healthcare system. Support groups can lighten the psychological burden of caregiving. Nonprofessionally facilitated (or peer) online caregiver support groups can help meet a critical need in healthcare as a low-cost resource for caregivers. Online caregiver peer support groups can promote the health and well-being of family caregivers and, by extension, the patients themselves, resulting in cost-savings for society. A better understanding of these types of groups is of critical importance, given the unrelenting pace of demographic shift in the United States. The purpose of this study was to examine content themes emerging from an unstructured, asynchronous online peer support group for family caregivers of people with chronic illness. Qualitative content analysis was used, yielding six themes: "experiencing the emotional toll," "need for catharsis/venting," "finding the silver linings," "seeking specific advice/problem solving," "realizing home is no longer a haven," and "adapting to the caregiver role." The themes reflect what emerged organically in an online support group that was not professionally facilitated or structured in any way. Heterogeneity in the relationship between caregivers and care recipients may negatively affect outcomes and requires further study.


New Polymeric Films with Antibacterial Activity Obtained by UV-induced Copolymerization of Acryloyloxyalkyltriethylammonium Salts with 2-Hydroethyl Methacrylate.
New polymeric films with antibacterial activity have been prepared, by simple UV-induced copolymerization of readily available ω-(acryloyloxy)-N,N,N-triethylalcan-1-aminium bromides (or acryloyloxyalkyltriethylammonium bromides, AATEABs) with commercially available 2-hydroethyl methacrylate (HEMA), at different relative amounts. In particular, the antibacterial activity of polymeric films derived from 11-(acryloyloxy)-N,N,N-triethylundecan-1-aminium bromide (or acryloyloxyundecyltriethylammonium bromide, AUTEAB; bearing a C-11 alkyl chain linker between the acrylate polymerization function and the quaternary ammonium moiety) and 12-(acryloyloxy)-N,N,N-triethyldodecan-1-aminium bromide (or acryloyldodecyltriethylammonium bromide, ADTEB, bearing a C-12 alkyl chain linker) has been assessed against Gram-negative Escherichia Coli and Gram-positive Staphylococcus aureus cells. The results obtained have shown a clear concentration-dependent activity against both bacterial strains, the films obtained from homopolymerization of pure AUTEAB and ADTEAB being the most effective. Moreover, ADTEAB-based films showed a higher antibacterial activity with respect to the AUTEAB-based ones. Interestingly, however, both types of films presented a significant activity not only toward Gram-positive S. aureus, but also toward Gram-negative E. Coli cells.


Tools for Open Source, Subnational CGE Modeling with an Illustrative Analysis of Carbon Leakage.
This paper introduces the Wisconsin National Data Consortium (WiNDC) framework for producing self-consistent accounts based on publicly available datasets that can be used in sub-national economic equilibrium analysis in the United States. We describe the process used to generate regional social accounting matrices and a calibrated static multi-regional, multi-sectoral computable general equilibrium model conformal with the constructed dataset. As illustration, we show how the core model can be applied for the analysis of energy-environment issues. We use an energy-economy extension of the core model to assess the effectiveness of several state level greenhouse gas mitigation proposals. Sub-national abatement measures result in carbon leakage - mandated reductions in controlled areas may be vitiated by increased emissions in uncontrolled jurisdictions. Using a WiNDC-based model, we calculate leakage rates and show how these depend on the underlying trade model. Our calculations demonstrate the importance of both data and modeling assumptions for the simulation of policy experiments.


Teaching research in undergraduate nursing education.
This textbook provides alternative ways of thinking about research and the use of research in nursing practice. New textbooks on nursing research may be written, curricula reorganized to provide a different emphasis on research, new teaching strategies applied, and new learning experiences offered; but, in the final analysis, the key to inculcating in students an excitement about inquiry in nursing rests with the faculty. Faculty clearly convey their own beliefs about research and its relevance for practice; they can encourage or dampen a student's interest and inquisitiveness about nursing phenomena, in part, by their own beliefs about inquiry and, in part, by their approach to students.


In Vitro Evaluation of the Interaction of Dextrin-Colistin Conjugates with Bacterial Lipopolysaccharide.
Dextrin-colistin conjugates have been developed with the aim of achieving reduced clinical toxicity associated with colistin, also known as polymyxin E, and improved targeting to sites of bacterial infection. This study investigated the in vitro ability of such dextrin-colistin conjugates to bind and modulate bacterial lipopolysaccharide (LPS), and how this binding affects its biological activity. These results showed that colistin and amylase-activated dextrin-colistin conjugate to a lesser extent induced aggregation of LPS to form a stacked bilayer structure with characteristic dimensions, although this did not cause any substantial change in its secondary structure. In biological studies, both colistin and dextrin-colistin conjugate effectively inhibited LPS-induced hemolysis and tumor necrosis factor α (TNFα) secretion in a concentration-dependent manner, but only dextrin-colistin conjugate showed no additive toxicity at higher concentrations. This study provides the first direct structural experimental evidence for the binding of dextrin-colistin conjugates and LPS and gives insight into the mode of action of dextrin-colistin conjugates.


Decreased Vector Gene Expression from E2b Gene-Deleted Adenovirus Serotype 5 Vaccines Intensifies Proinflammatory Immune Responses.
Recombinant adenovirus serotype 5 (Ad5) vectors are promising vaccine candidates due to their intrinsic immunogenicity and potent transgene expression; however, widespread preexisting Ad5 immunity has been considered a developmental impediment to the use of traditional, or conventional, E1 and E3 gene-deleted Ad5 (Ad5[E1-]) vaccines. Even in the presence of anti-Ad5 immunity, recent murine and human studies have confirmed E2b gene-deleted Ad5 (Ad5[E1-,E2b-]) vaccines to be highly efficacious inducers of transgene-specific memory responses and significantly less toxic options than Ad5[E1-] vaccines. While these findings have been substantially confirmed, the molecular mechanisms underlying the different reactions to these vaccine platforms are unknown. Using cultures of human peripheral blood mononuclear cells (hPBMCs) derived from multiple human donors, we found that Ad5[E1-,E2b-] vaccines trigger higher levels of hPBMC proinflammatory cytokine secretion than Ad5[E1-] vaccines. Interestingly, these responses were generated regardless of the donors' preexisting anti-Ad5 humoral and cell-mediated immune response status. In vitro hPBMC infection with the Ad5[E1-,E2b-] vaccine also provoked greater Th1-dominant gene responses yet smaller amounts of Ad-derived gene expression than Ad5[E1-] vaccines. These results suggest that Ad5[E1-,E2b-] vaccines, in contrast to Ad5[E1-] vaccines, do not promote activities that suppress innate immune signaling, thereby allowing for improved vaccine efficacy and a superior safety profile independently of previous Ad5 immunity.


Utility of Th1-cell immune responses for distinguishing active tuberculosis from non-active tuberculosis: A case-control study.
Currently available Interferon-γ release assay (IGRA) cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). A study was performed to evaluate the value of Mycobacterium tuberculosis (MTB) specific Th1 cell immune responses which test IFN-γ and IL-2 simultaneous for differentiating ATB from non-ATB. Forty-nine newly diagnosed inpatients with ATB (26 pulmonary TB and 23 extrapulmonary TB) were enrolled as the ATB group. Forty-five volunteers with latent tuberculosis infection (LTBI) and twenty with evidence of previous TB were enrolled during the same period as the non-ATB group. Clinical examination and MTB specific Th1 cell immune responses were performed for all participants. After being stimulated with ESAT-6 and CFP-10, the median frequencies of single IL-2-, single IFN-γ-, and dual IFN-γ/IL-2-secreting T-cells were all higher in the ATB group than in the non-ATB group (20(8-45) vs. 7(3-13), P<0.001;131(44-308) vs. 10(6-27), P<0.001;25(9-74) vs. 7(3-23), P = 0.001, respectively). Evaluation of the diagnostic performance of detecting single IFN-γ-secreting T cells for pulmonary TB employed a cutoff value of 35 iSFCs/250,000 PBMC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 92.3%, 80.0%, 64.9%, 96.3%, 4.62, and 0.10, respectively. For extrapulmonary TB, using a cutoff value of 23 iSFCs/ 250,000 PBMC, the sensitivity, specificity, PPV, NPV, PLR, and NLR were 91.3%, 76.9%, 58.3%, 96.2%, 3.96, and 0.11, respectively. When combining frequencies and proportion of single IFN-γ-secreting T cells, the test sensitivity was 100% in parallel tests and the specificity was 87.7% in serial tests for pulmonary TB. MTB specific Th1 cell immune responses (FluoroSpot) had value for the differentiation of ATB and non-ATB. Further confirmatory studies are indicated.


A cluster randomized controlled trial of a modified vaccination clinical reminder for primary care providers.
Adult vaccination rates in the United States fall short of national goals, and rates are particularly low for Black Americans. We tested a provider-focused vaccination uptake intervention: a modified electronic health record clinical reminder that bundled together three adult vaccination reminders, presented patient vaccination history, and included talking points for providers to address vaccine hesitancy. Primary care teams at the Atlanta Veterans Affairs Medical Center, who saw 28,941 patients during this period, were randomly assigned to receive either the modified clinical reminder (N = 44 teams) or the status quo (N = 40 teams). Uptake of influenza and other adult vaccinations was 1.6 percentage points higher in the intervention group, which was not statistically significant (confidence interval, CI [-1.3, 4.4], p = .28). The intervention had similar effects on Black and White patients and did not reduce the disparity in vaccination rates between these groups. Provider-focused interventions are a promising way to address vaccine hesitancy, but they may need to be more intensive than a modified clinical reminder to have appreciable effects on vaccination uptake. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Mixotrophic in vitro cultivations: the way to go astray in plant physiology.
Rate of photosynthesis and related plant carbohydrate status are crucial factors affecting plant vigor. Sugars providing carbon and energy sources serve also as important signaling molecules governing plant growth and development through a complex regulatory network. These facts are often neglected when mixotrophic cultivation of plants in vitro is used, where artificial exogenous sugar supply hinders studies of metabolism as well as sugar-driven developmental processes. We compared the growth, selected gas-exchange parameters and sugar metabolism characteristics in four model plants, potato (Solanum tuberosum 'Lada'), tobacco (Nicotiana tabacum 'Samsun'), rapeseed (Brassica napus 'Asgard') and strawberry (Fragaria vesca), under both photomixotrophic (PM) and photoautotrophic (PA) conditions. To ensure PA conditions, we used our improved sun caps that serve as gas and light permeable covers for cultivation vessels. We found bigger biomass accumulation, larger leaf areas, higher stomatal conductance and higher instantaneous water use efficiency and lower root sugar contents in PA plants compared to PM ones. However, for other characteristics (root biomass, root/shoot ratio, pigment contents, leaf sugar and starch levels and transpiration rates), a strong species-dependent reactions to the exogenous sugar supply was noted, which does not allow to create a general view on the overall impact of PM nutrition under in vitro conditions.


Repair of vesicouterine fistula by not using traditional O' connor method.
A 25-year-old female patient visited our clinic with complaint of cyclic haematuria. She had previous two Caesarean Sections at a secondary care hospital. Her complete urinalysis showed abundant red blood cells. Through computed tomography a fistula tract between the posterior wall of the bladder and the anterior wall of the lower uterine segment was diagnosed. The Cystoscopy revealed a fistulous opening with a diameter of nearly 1.5 cm localized between the bladder and uterine cavity. Fistulae was repaired by abdominal approach without transection of bladder. Surgery was performed by mobilization of bladder and wide anterior uterine dissection. A 2cm defect in the lower uterine segment was identified and was closed with 0 polyglycolic acid suture. Bladder defect was repaired in two layers and omental tissue flap was placed between the two surfaces. At 6 months follow the up patient was asymptomatic.


N-heterocyclic carbene-functionalized metal-organic frameworks for the chemical fixation of CO2.
N-heterocyclic carbenes (NHCs) are a class of molecules with a lone pair of carbene electrons and thus, they have the ability to activate CO2 to form imidazolium carboxylates. The incorporation of activated, metal-free NHC moieties into metal-organic frameworks (MOFs) without the decomposition of metal-carboxylate coordination motifs is highly desired owing to the high CO2 affinity and versatile chemical functionalities in MOFs. Herein, we have summarized the recent in situ generation approaches to form metal-free NHC-functionalized MOFs, which are a unique class of CO2-conversion catalysts with high catalytic activity, selectivity and stability, superior to those of homogenous and other heterogeneous NHC analogues. The NHC-functionalized MOFs for catalytic CO2 reduction include reactions such as the hydroboration of CO2, hydrosilylation of CO2, N-methylation using CO2 and hydrogenation of CO2 to formic acid. Overall, the synthetic strategy of metal-free NHC-functionalized MOFs, the unique catalytic pathways of NHC-functionalized MOFs, and potentially new research directions of NHC-functionalized MOFs are discussed, which will guide researchers to attempt to design new NHC-MOFs and extend their catalytic applications in the chemical fixation of CO2.


Borderline personality disorder and the diagnostic co-occurrence of mental health disorders and somatic diseases: A controlled prospective national register-based study.
Information on borderline personality disorder (BPD) and its comorbidities is often limited to concentrate on a few diagnoses. The aim of the study was to use national register data to investigate all diagnostic co-occurring mental health disorders and somatic diseases 3 years before and after initial BPD diagnosis compared with a matched control group. The study was a register-based cohort of 2756 patients with incident BPD (ICD F60.3) and 11,024 matched controls, during 2002-2016. Comorbidity data were classified into main disease groups, in accordance with the World Health Organization ICD-10 criteria. Almost half the patients had been diagnosed with mental and behavioral disorders before the BPD diagnosis as compared to 3% in the control group. Further, the co-occurrence of diseases due to external causes of morbidity, including injury, self-harm, and poisoning were more represented in the BPD group before diagnosis as compared to the control group. In addition, co-occurring morbidity related to diseases in the circulatory, the respiratory, the digestive, the musculoskeletal, and the genitourinary system was more represented in the BPD group. After diagnosis, the proportion of patients with co-occurring morbidity increased further in all main disease groups in the BPD group. As many as 87% of patients had mental and behavioral co-occurring morbidity and 15% nervous diseases as compared with 3% and 4%, respectively, in the control group. Also, comorbidities related to external causes of morbidity, including for example, injury and self-harm were more represented in the BPD group. The BPD group had more somatic co-occurring morbidity, especially digestive, respiratory, circulatory, and endocrine diseases. Finally, the mortality over 12 years was statistically significantly higher in people with BPD than in the control group. Patients with BPD have higher odds for multiple physical health conditions and co-occurrence of mental health disorders.


Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery: Protocol for a single-center prospective observational study.
The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft after esophageal reconstruction. Clinical judgment is unreliable in determining graft perfusion. Therefore, an objective, validated, and reproducible method is urgently needed. Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an emerging and promising modality. This study's objectives are to evaluate the feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion and to validate ICGA by comparison with hemodynamic parameters, blood and tissue expression of hypoxia-induced markers, and tissue mitochondrial respiration rates. And, second, to evaluate its ability to predict AL in patients after minimally invasive esophagectomy (MIE). Patients (N = 70) with resectable esophageal cancer will be recruited for standard MIE. ICGA will be performed after graft creation and thoracic pull-up. Dynamic digital images will be obtained starting after intravenous bolus administration of ICG. The resulting images will be subjected to curve analysis and to compartmental analysis based on the adiabatic approximation to tissue homogeneity kinetic model. The calculated perfusion parameters will be compared to intraoperative hemodynamic data to evaluate the effects of patient hemodynamics. To verify whether graft perfusion represents tissue oxygenation, ICGA perfusion parameters will be compared with systemic and serosa lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia-related markers and mitochondrial chain respiratory rate. Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict AL and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses. The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during MIE, potentially reducing the incidence of AL and its associated severe morbidity and mortality. Clinicaltrials.gov registration number is NCT03587532. The study was approved by the ethical committee of the Ghent University, Belgium (B670201836427).


What is the role of fresh groundwater and recirculated seawater in conveying nutrients to the coastal ocean?
Submarine groundwater discharge (SGD) is a major process operating at the land-sea interface. Quantifying the SGD nutrient loads and the marine/terrestrial controls of this transport is of high importance, especially in oligotrophic seas such as the eastern Mediterranean. The fluxes of nutrients in groundwater discharging from the seafloor at Dor Bay (southeastern Mediterranean) were studied in detail using seepage meters. Our main finding is that the terrestrial, fresh groundwater is the main conveyor of DIN and silica to the coastal water, with loads of 500 and 560 mol/yr, respectively, per 1 m shoreline. Conversely, recirculated seawater is nutrient-poor, and its role is mainly as a dilution agent. The nutrient loads regenerated in the subterranean estuary (sub-bay sediment) are relatively small, consisting mostly of ammonium (24 mol/yr). On the other hand, the subterranean estuary at Dor Bay sequesters as much as 100 mol N/yr per 1 m shoreline, mainly via denitrification processes. These, and observations from other SGD sites, imply that the subterranean estuary at some coastal systems may function more as a sink for nitrogen than a source. This further questions the extent of nutrient contributions to the coastal water by some subterranean estuaries and warrants systematic evaluation of this process in various hydrological and marine trophic conditions.


Comparative analysis of chloroplast genomes in Vasconcellea pubescens A.DC. and Carica papaya L.
The chloroplast genome is an integral part of plant genomes in a species along with nuclear and mitochondrial genomes, contributing to adaptation, diversification, and evolution of plant lineages. In the family Caricaceae, only the Carica papaya chloroplast genome and its nuclear and mitochondrial genomes were sequenced, and no chloroplast genome-wide comparison across genera was conducted. Here, we sequenced and assembled the chloroplast genome of Vasconcellea pubescens A.DC. using Oxford Nanopore Technology. The size of the genome is 158,712 bp, smaller than 160,100 bp of the C. papaya chloroplast genome. And two structural haplotypes, LSC_IRa_SSCrc_IRb and LSC_IRa_SSC_IRb, were identified in both V. pubescens and C. papaya chloroplast genomes. The insertion-deletion mutations may play an important role in Ycf1 gene evolution in family Caricaceae. Ycf2 is the only one gene positively selected in the V. pubescens chloroplast genome. In the C. papaya chloroplast genome, there are 46 RNA editing loci with an average RNA editing efficiency of 63%. These findings will improve our understanding of the genomes of these two crops in the family Caricaceae and will contribute to crop improvement.


[Clinical, surgical and diagnostic evaluation of lesions of the oral mucosa using biopsy and histological studies: comparison of two methods].
In this study, the authors evaluated the clinical and histologic efficacy of electrosurgery (DTC 100) in performing excisional biopsy on benign mucosal lesions, in comparison with traditional surgery (scalpel and suture). For this aim, 40 biopsy specimens were selected and divided into 4 distinct groups: group A1, samples of oral lesions located on the genian mucosa and removed using DTC 100; group A2, samples of healthy genian mucosa removed using DTC 100, as control; group B1, samples of oral lesions located on the genian mucosa and removed using traditional surgery; group B2, samples of healthy genian mucosa removed using traditional surgery, as control. The clinical evaluation was carried out regarding symptomatology and bleeding after surgery, healing time, restitutio ad integrum. It gives positive results for the electrosurgical technique, in which the suture is not necessary. The histologic evaluation regarding the microscopical adequacy of specimens removed by means of electrosurgery shows better results than those from other authors; in fact, the presence of the cauterized margin compromize minimally the possibility of examining specimens of adequate size; the dimension of the cauterized margin also depends on various factors: the use of only the tomic function of the electroscalpel with the correct setting; the skill of the surgeon who should apply neither pressure or resistance; the speed of incision; the use, when possible, of acicular and thin blades.


An Indirect Treatment Comparison of Semaglutide 2.0 mg vs Dulaglutide 3.0 mg and 4.5 mg Using Multilevel Network Meta-regression.
Currently, no head-to-head data are available comparing semaglutide 2.0 mg with dulaglutide 3.0 mg or 4.5 mg. We conducted an indirect treatment comparison (ITC) of their effects on glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. Multilevel network meta-regression was conducted, based on a connected evidence network of published results from the A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes 11 trial and individual patient data from the A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes (SUSTAIN) and SUSTAIN 7 trials. Semaglutide 2.0 mg significantly reduced HbA1c vs dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETDs) of -0.44% points (95% credible interval [CrI], -0.68 to -0.19) and -0.28% points (95% CrI, -0.52 to -0.03), respectively. Semaglutide 2.0 mg also significantly reduced body weight vs dulaglutide 3.0 mg and 4.5 mg with ETDs of -3.29 kg (95% CrI, -4.62 to -1.96) and -2.57 kg (95% CrI, -3.90 to -1.24), respectively. Odds of achieving HbA1c < 7.0% were significantly greater for semaglutide 2.0 vs dulaglutide 3.0 mg (odds ratio [OR]: 2.23 [95% CrI, 1.15-3.90]), whereas this did not reach significance for semaglutide 2.0 mg vs dulaglutide 4.5 mg (OR: 1.58 [95% CrI, 0.82-2.78]). Sensitivity analyses supported the main analysis findings. This ITC demonstrated significantly greater reductions from baseline in HbA1c and body weight with semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg. The findings of this study provide important comparative effectiveness information until randomized head-to-head studies become available.


Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study.
Adipocyte-derived secretory proteins have been increasingly linked to diabetes. To investigate whether adiponectin, a major adipocyte secretory protein, predicts diabetes, we conducted a case-cohort study representing the approximately 9-year experience of the 10,275 middle-aged, U.S. African-American and white participants of the Atherosclerosis Risk in Communities (ARIC) study. Adiponectin was measured on stored plasma of 581 incident diabetes case subjects and 572 noncase subjects. Overall hazard ratios (95% CIs) for developing diabetes, for those in the second, third, and fourth (versus the first) quartile of adiponectin were 0.57 (0.41-0.78), 0.39 (0.27-0.56), and 0.18 (0.11-0.27), respectively, after adjustment for age, sex, ethnicity, study center, parental history of diabetes, and hypertension and 0.72 (0.48-1.09), 0.67 (0.43-1.04), and 0.58 (0.34-0.99), respectively, after additional adjustment for BMI, waist-to-hip ratio, fasting glucose, insulin, and a score composed of six inflammation markers. The association was of similar magnitude in men and women and in whites and African Americans, but was absent in smokers and in those with a greater inflammation score (interaction P < 0.01 for each). In conclusion, in this community-based sample of U.S. adults, higher adiponectin levels were associated with a lower incidence of diabetes.


Sex determination in Drosophila: The view from the top.
One of the most important decisions in development is whether to be male or female. In Drosophila melanogaster, most cells make this choice independent of their neighbors such that diploid cells with one X chromosome (XY) are male and those with two X chromosomes (XX) are female. X-chromosome number is relayed through regulatory proteins that act together to activate Sex-lethal (Sxl) in XX animals. The resulting SXL female specific RNA binding protein modulates the expression of a set of downstream genes, ultimately leading to sexually dimorphic structures and behaviors. Despite the apparent simplicity of this mechanism, Sxl activity is controlled by a host of transcriptional and posttranscriptional mechanisms that tailor its function to specific developmental scenarios. This review describes recent advances in our understanding of Sxl regulation and function, highlighting work that challenges some of the textbook views about this classical (often cited, yet poorly understood) binary switch gene.


Microsecond molecular dynamics simulations of the kinetic pathways of gas hydrate formation from solid surfaces.
In this paper, we report microsecond molecular dynamics simulations of the kinetic pathway of CO(2) hydrate formation triggered by hydroxylated silica surfaces. Our simulation results show that the nucleation of the CO(2) hydrate is a three-stage process. First, an icelike layer is formed closest to the substrates on the nanosecond scale. Then, on the submicrosecond timescale, a thin layer with intermediate structure is induced to compensate for the structure mismatch between the icelike layer and the final stable CO(2) hydrate. Finally, on the microsecond timescale, the nucleation of the first CO(2) hydrate motif layer is generated from the intermediate structure that acts as nucleation seeds. We also address the effects of the distance between two surfaces.


Transcriptomes reveal genetic signatures underlying physiological variations imposed by different fermentation conditions in Lactobacillus plantarum.
Lactic acid bacteria (LAB) are utilized widely for the fermentation of foods. In the current post-genomic era, tools have been developed that explore genetic diversity among LAB strains aiming to link these variations to differential phenotypes observed in the strains investigated. However, these genotype-phenotype matching approaches fail to assess the role of conserved genes in the determination of physiological characteristics of cultures by environmental conditions. This manuscript describes a complementary approach in which Lactobacillus plantarum WCFS1 was fermented under a variety of conditions that differ in temperature, pH, as well as NaCl, amino acid, and O(2) levels. Samples derived from these fermentations were analyzed by full-genome transcriptomics, paralleled by the assessment of physiological characteristics, e.g., maximum growth rate, yield, and organic acid profiles. A data-storage and -mining suite designated FermDB was constructed and exploited to identify correlations between fermentation conditions and industrially relevant physiological characteristics of L. plantarum, as well as the associated transcriptome signatures. Finally, integration of the specific fermentation variables with the transcriptomes enabled the reconstruction of the gene-regulatory networks involved. The fermentation-genomics platform presented here is a valuable complementary approach to earlier described genotype-phenotype matching strategies which allows the identification of transcriptome signatures underlying physiological variations imposed by different fermentation conditions.


Tunable 1D van der Waals Nanostructures by Vapor-Liquid-Solid Growth.
ConspectusVapor-liquid-solid (VLS) growth using molten metal catalysts has traditionally been used to synthesize nanowires from different 3D-crystalline semiconductors. With their anisotropic structure and properties, 2D/layered semiconductors create additional opportunities for materials design when shaped into 1D nanostructures. In contrast to hexagonal 2D crystals such as graphene, h-BN, and transition metal dichalcogenides, which tend to roll up into nanotubes, VLS growth of layered group III and group IV monochalcogenides produces diverse nanowire and nanoribbon morphologies that crystallize in a bulk-like layered structure with nanometer-scale footprint and lengths exceeding tens of micrometers. In this Account, we discuss the achievable morphologies, the mechanisms governing key structural features, and the emerging functional properties of these 1D van der Waals (vdW) architectures. Recent results highlight rich sets of phenomena that qualify these materials as a distinct class of nanostructures, far beyond a mere extension of 3D-crystalline VLS nanowires to vdW crystals.The main difference between 3D- and vdW crystals, the pronounced in-plane/cross-plane anisotropy of layered materials, motivates investigating the factors governing the layer orientation. Recent research suggests that the VLS catalyst plays a key role, and that its modification via the choice of chalcogens or through modifiers added to the growth precursor can switch both the nanostructure morphology and vdW layering. In many instances, ordinary layered structures are not formed but VLS growth is dominated by morphologies─often containing a crystal defect─that present reduced or vanishing layer nucleation barriers, thus achieving fast growth and emerging as the principal synthesis product. Prominent defect morphologies include vdW bicrystals growing by a twin-plane reentrant process and chiral nanowires formed by spiral growth around an axial screw dislocation. The latter carry particular promise, e.g., for twistronics. In vdW nanowires, Eshelby twist─a progressive crystal rotation caused by the dislocation stress field─translates into interlayer twist that is precisely tunable via the wire diameter. Projected onto a helicoid vdW interface, the resulting twist moirés not only modify the electronic structure but also realize configurations without equivalent in planar systems, such as continuously variable twist and twist homojunctions.1D vdW nanostructures derive distinct functionality from both their layered structure and embedded defects. Correlated electron microscopy methods including imaging, nanobeam diffraction, as well as electron-stimulated local absorption and luminescence spectroscopies combine to an exceptionally powerful probe of this emerging functionality, identifying twist-moiré induced electronic modulations and chiral photonic modes, demonstrating the benign nature of defects in optoelectronics, and uncovering ferroelectricity via symmetry-breaking by single-layer stacking faults in vdW nanowires. Far-reaching possibilities for tuning crystal structure, morphology, and defects create a rich playground for the discovery of new functional nanomaterials based on vdW crystals. Given the prominence of defects and extensive prospects for controlling their character and placement during synthesis, 1D vdW nanostructures have the potential to cause a paradigm shift in the science of electronic materials, replacing the traditional strategy of suppressing crystal imperfections with an alternative philosophy that embraces the use of individual defects with designed properties as drivers of technology.


Genetic variability in melatonin concentrations in ewes originates in its synthesis, not in its catabolism.
We investigated whether the genetic difference in plasma melatonin concentration in ewes was due to differences in the synthesis pathway from the pineal gland or in the catabolism of the hormone. Two groups of ewes [9 low (L) and 10 high (H)] were selected according to the breeding value of their mean nighttime plasma melatonin concentrations estimated at winter and summer solstices. In response to an identical dose of melatonin administered intravenously at 9:00 AM, no differences between groups were observed for any of the kinetic parameters: clearance rate, steady-state volume of distribution, terminal half-lives, and mean residence times. In the second experiment, two series of frequent blood samples were performed, one in the middle of the dark phase with samples taken every 5 min, and the other over 24 h with hourly samples. Highly significant differences between groups in nocturnal melatonin production rate were observed (L: 25.7 +/- 2.8 vs. H: 63.1 +/- 8.9 microg . kg-1 . h-1, P < 0.01). Thus the genetic differences in plasma melatonin concentrations in ewes originate in the synthesis pathway of the melatonin from the pineal gland rather than from differences in the catabolism of the hormone.


Acute rhabdomyolysis and myonecrosis complicating aeromonas bacteremia in neutropenic patients with hematologic malignancies: report of two cases.
Infections by Aeromonas spp. are a rare cause of systemic infection in normal and immunocompromised hosts. We report the cases of two patients with acute non-lymphoblastic leukemia who developed septic shock by Aeromonas species with unusual soft-tissue complications. One patient who was undergoing consolidation chemotherapy developed septic shock by Aeromonas hydrophila with rhabdomyolysis and subsequent soft-tissue destruction consistent with myonecrosis. She recovered with combination antibiotic therapy and supportive care. The second patient developed neutropenia due to ganciclovir treatment for post-allogeneic transplant cytomegalovirus antigenemia. He developed a rapidly progressive septic shock due to Aeromonas sobria with rhabdomyolysis, multi-organ failure and bilateral lower limb myonecrosis, and died within 48 hours. The portal of entry was not identified in either case. These cases confirm the potentially aggressive nature of these bacteria in neutropenic cancer patients with an unusual tendency to produce muscular and soft-tissue destruction.


Placebo insight: the rationality of insight-oriented psychotherapy.
It is widely believed that the insight-oriented psychotherapies provide their clients with valid methods of self-exploration that lead to bona fide self-knowledge. It also is widely believed that clients' insights must be true in order to be therapeutically effective. Both these claims are implausible. I argue that because clients face significant epistemic pressures in the therapeutic encounter, the insight-oriented psychotherapies are highly susceptible to generating placebo insights, that is, illusions, deceptions, and adaptive self-misunderstandings that convincingly mimic veridical insight but have no genuine explanatory power. The insight-oriented psychotherapies also are highly susceptible to generating therapeutic artefacts that appear to confirm the insights acquired by clients. The powerful treatment methods to which clients are subjected generate some of the very psychological and behavioral facts that clients claim to "discover" in their explorations. This impugns the scientific status of the insight-oriented psychotherapies.


Effect of Dry-Aged Beef Crust Levels on Quality Properties of Brown Sauce.
This study utilized the crust by-product from dry-aged beef as a flavor enhancer for brown sauce and analyzed its physicochemical and organoleptic properties. The physiochemical properties include proximate composition, color, pH, swelling yield, viscosity, and salinity. The organoleptic properties were studied through electronic nose and sensory evaluations. The moisture content of the samples decreased while fat and protein content increased as crust content increased (p<0.05). The lightness, yellowness, and redness increased with increasing crust content (p<0.05). The pH of the samples also increased as the crust content increased. The viscosity significantly increased while salinity decreased with increasing crust content (p<0.05). The aromatic profiles of the control and samples with 5% and 10% crust addition were distinguishable; however, samples with crust additives between 10% and 15% gave similar aromatic profiles. The taste of the control sample was significantly lower than that of the samples formulated with the crust (p<0.05), and the sensory viscosity of the samples with 10% crust was significantly higher than that of the control (p<0.05). Flavor and overall acceptability tended to increase with increasing crust content of up to 10% addition (p<0.05). These results show that the crust from dry-aged beef loin crust is a suitable natural flavor enhancer for brown sauce and improves its physiochemical and organoleptic properties.


Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility.
Axoplasm from the squid giant axon contains a soluble protein translocator that induces movement of microtubules on glass, latex beads on microtubules, and axoplasmic organelles on microtubules. We now report the partial purification of a protein from squid giant axons and optic lobes that induces these microtubule-based movements and show that there is a homologous protein in bovine brain. The purification of the translocator protein depended primarily on its unusual property of forming a high affinity complex with microtubules in the presence of a nonhydrolyzable ATP analog, adenylyl imidodiphosphate. The protein, once released from microtubules with ATP, migrates on gel filtration columns with an apparent molecular weight of 600 kilodaltons and contains 110-120 and 60-70 kilodalton polypeptides. This protein is distinct in molecular weight and enzymatic behavior from myosin or dynein, which suggests that it belongs to a novel class of force-generating molecules, for which we propose the name kinesin.


Terminology of psychogenic nonepileptic seizures.
Several different terms have been used to describe "psychogenic nonepileptic seizures" (PNES) in the literature. In this study, we evaluated the most common English terms used to describe PNES on Google and in PubMed using multiple search terms (https://www.google.com and http://www.ncbi.nlm.nih.gov/pubmed). The information prevalence of the five terms most frequently used to refer to PNES in PubMed were: psychogenic non(-)epileptic seizure(s), followed by pseudo(-)seizure(s), non(-)epileptic seizure(s), psychogenic seizure(s), and non(-)epileptic event(s). The five most frequently adopted terms to describe PNES in Google were: psychogenic non(-)epileptic seizure(s), followed by non(-)epileptic event(s), psychogenic attack(s), non(-)epileptic attack(s), and psychogenic non(-)epileptic attack(s). The broad spectrum of synonyms used to refer to PNES in the medical literature reflects a lack of internationally accepted, uniform terminology for PNES. In addition to "seizure(s)," lay people use the word "attack(s)" to describe PNES. Although considered obsolete, some terms, e.g., pseudoseizure(s), are still used in the recent medical literature. Adopting a uniform terminology to describe PNES could facilitate communication between epileptologists, physicians without specific expertise in epilepsy, and patients.


[Microangiographic signs of blood vessel rearrangement during tumor growth].
In the experiment performed in mice with a subcutaneously implanted sarcoma-37 on the chin, rearrangement of the blood vessels has been followed by means of micro-roentgenography. In the process of the implanted tumour growth, the blood vessels undergo a profound functional-anatomical rearrangement, which develops, beginning from the first hours, in two ways: at the expense of the peripheral vessels rearrangement in the recepient and at the expense of real tumorous vessels development ensuaring vascular trophic of the tumour.


Left occipital and right frontal involvement in syntactic category prediction: MEG evidence from Standard Arabic.
Though recent years have seen a growth in research on predictive processes in language comprehension, their scope and mechanisms remain partially elusive. While mechanisms involved in predicting specific words are relatively well understood, those underlying syntactic prediction are still unclear. In part, this is because of the difficulty in designing experiments that manipulate syntactic predictability while controlling other variables. In this MEG study, we achieved this with a manipulation of syntactic category predictability within fully well-formed expressions of Standard Arabic. Participants read sentences beginning with a subject-adjective context, in which the presence of at least one of two possible cues (gender-incongruity and/or an intervening relative pronoun) was sufficient for predicting a target word's syntactic category. Absence of both cues (i.e., congruent subject-adjective context with no relative pronoun) increased uncertainty about the target's syntactic category. Using source analysis, we compared activity evoked by targets with predictable and unpredictable categories in the occipital lobe. We found an interaction effect consistent with previous findings: in the primary visual cortex, an early evoked component (visual M100) is enhanced only when the syntactic category was unpredictable. We also compared responses to pre-target predictive and unpredictive contexts across five bilateral frontal and temporal regions. In the right-hemispheric frontal region, we found a temporal cluster (~230 ms after adjective onset), where unpredictive contexts elicited more activation than predictive contexts. By hypothesis elimination, we conclude that the most likely variable driving this effect is syntactic entropy. Our results show that predictive mechanisms recruited during reading also involve predicting upcoming syntactic categories, implicating at least two cortical regions: the left visual cortex and the right frontal cortex.


Fatigue Failure in Extra-Articular Proximal Tibia Fractures: Locking Intramedullary Nail Versus Double Locking Plates-A Biomechanical Study.
The goal of this study is to compare the fatigue strength of a locking intramedullary nail (LN) construct with a double locking plate (DLP) construct in comminuted proximal extra-articular tibia fractures. Eight pairs of fresh frozen cadaveric tibias with low bone mineral density [age: 80 ± 7 (SD) years, T-score: -2.3 ± 1.2] were used. One tibia from each pair was fixed with LN, whereas the contralateral side was fixed with DLP for complex extra-articular multifragmentary metaphyseal fractures (simulating OTA 41-A3.3). Specimens were cyclically loaded under compression simulating single-leg stance by staircase method out to 260,000 cycles. Every 2500 cycles, localized gap displacements were measured with a 3D motion tracking system, and x-ray images of the proximal tibia were acquired. To allow for mechanical settling, initial metrics were calculated at 2500 cycles. The 2 groups were compared regarding initial construct stiffness, initial medial and lateral gap displacements, stiffness at 30,000 cycles, medial and lateral gap displacements at 30,000 cycles, failure load, number of cycles to failure, and failure mode. Failure metrics were reported for initial and catastrophic failures. DLP constructs exhibited higher initial stiffness and stiffness at 30,000 cycles compared with LN constructs (P < 0.03). There were no significant differences between groups for loads at failure or cycles to failure. For the fixation of extra-articular proximal tibia fractures, a LN provides a similar fatigue performance to double locked plates. The locked nail could be safely used for fixation of proximal tibia fractures with the advantage of limited extramedullary soft tissue damage.