Introduction: A family systems approach to promote maternal, child and adolescent nutrition.
In all cultures, women and children are embedded in family systems that determine roles, relationships, patterns of communication and authority between family members. Especially in non-western societies, maternal and child nutrition practices are determined not only by the biological parents but also by other influential family members. Most maternal and child nutrition research and interventions do not consider the constellation of family roles and influence on women and children and continue to focus on the mother-child dyad and individual knowledge, attitudes and practices. There is growing agreement on the need to adopt an ecological framework to address public health issues, including those dealing with maternal and child nutrition. This special issue presents examples of research from a variety of settings that employed an ecological, family systems approach either to investigate maternal, child or adolescent nutrition issues or to design interventions that engaged various actors within family settings. These 11 articles contribute to a growing body of evidence supporting the relevance of a wider family systems perspective for nutrition research and interventions. Key themes across studies include the limitations of using a nuclear family model for research and intervention design, the need for formative research that comprehensively explores family systems, increasing recognition of the extensive involvement and support provided by grandmothers, and the importance of engaging men in culturally appropriate ways based on community dialogue and women's perspectives. Future maternal and child nutrition research and interventions can be strengthened by systems thinking that acknowledges that individuals are situated within family and community systems.


Modulation of MDR1 and MRP3 gene expression in lung cancer cells after paclitaxel and carboplatin exposure.
Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.


Identification of 14-3-3sigma mutation causing cutaneous abnormality in repeated-epilation mutant mouse.
Repeated-epilation (Er) mutation in the mouse is inherited as an autosomal and semidominant mutation. Major defects in heterozygous adults and homozygous fetuses were associated with skin and were caused by abnormal ectodermal differentiation. Heterozygous mice are characterized by repeated hair loss and regrowth, and homozygous fetuses die at birth with severe abnormality in skin, limb, tail, and face. To identify the gene causing Er mutation, we have performed gene-expression profiles of skins and mouse embryonic fibroblasts from WT and mutant Er mice by using Affymetrix (Santa Clara, CA) chip analysis. By analyzing the candidate genes generated from gene-expression profiling, we identified a Sfn mutation in Er mice. A single nucleotide insertion in the Sfn (Stratifin, also called 14-3-3sigma) coding region results in a truncated protein lacking 40 amino acid residues at the C terminus. The mutation is linked with phenotypes of Er-heterozygous and -homozygous mice. Ectopic overexpression of WT 14-3-3sigma in Er/Er keratinocytes rescues defects in keratinocyte differentiation. Our study demonstrates that 14-3-3sigma is a crucial regulator for skin proliferation and differentiation.


Celiac disease detection in hypothyroid patients requiring elevated thyroid supplementation: A prospective cohort study.
Celiac disease (CD) is associated with hypothyroidism, but the disease prevalence is not thought to be great enough to warrant testing all hypothyroid patients. We hypothesized that hypothyroid patients with concomitant CD would require elevated doses of levothyroxine, and there is a threshold daily dose, above which, hypothyroid patients should be tested for CD. Hypothyroid patients presenting to the endoscopy or endocrinology clinics at the University of Vermont Medical Center were included. Patients were categorized by whether or not they required ≥125mcg/day of levothyroxine. A serum tissue transglutaminase (tTG) was performed on enrolled patients. Patients with an elevated serum tTG underwent endoscopy with duodenal biopsies. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. Overall, 500 patients were enrolled and 29% (144 patients) required ≥125mcg/day of levothyroxine. CD was detected in 9 patients. The prevalence of CD ranged from 1.8% in our entire cohort to 12.5% in patients requiring ≥200mcg/day of levothyroxine. Eight patients with CD (89%) required ≥125mcg/day of levothyroxine. Patients who required ≥125mcg/day of levothyroxine had a significantly increased risk of CD (p<0.001). CD was detected in 5.6% of patients requiring ≥125mcg/day of levothyroxine. Hypothyroid patients requiring elevated daily doses of levothyroxine are more likely to have CD. Hypothyroid patients requiring ≥125mcg/day of levothyroxine should undergo serologic testing for CD.


Anti-HCV positivity in sexual partners and offspring of patient with chronic hepatitis C.
We investigated the seroprevalence of HCV in stable sexual partners and offspring of chronic hepatitis C patients, and aimed to determine the risk factors involved. 191 anti-HCV and HCV RNA positive subjects who coinhabited with their spouse and/or offspring were included. Risk factors of index cases for disease transmission, liver biopsy results, anti-HCV and HCV-RNA in spouses and/or offspring were evaluated. Together with index cases, a total of 404 family members including 174 stable sexual partners and 230 offspring were included. The most common risk factors among index cases were dental procedures (73.8%), history of surgery (64.9%), and blood transfusions (24.1%). Anti-HCV positivity was established in 11 (2.7%) of the total 404 family contacts--6 sexual partners and 5 offspring. HCV seropositivity was significantly higher in the spouses of index cases with severe hepatitis C compared to those with mild to moderate hepatitis C (p=0.008), but there was no statistically significant correlation between the severity of liver disease in index cases and anti-HCV positivity in their offspring. In conclusion, anti-HCV seropositivity in the spouses and children of patients who are HCV-RNA positive HCV carriers does not appear to be higher than the HCV seroprevalence in our country.


[Dual-energy subtraction radiography of the breast].
Dual-energy projection radiography was applied to breast examination. To perform the dual-energy subtraction radiography using a digital radiography unit, high and low-energy exposures were made at an appropriate time interval under differing X-ray exposure conditions. Dual-energy subtraction radiography was performed in 41 cancer patients in whom the tumor shadow was equivocal or the border of cancer infiltration was not clearly demonstrated by compression mammography, and 15 patients with benign diseases such as fibrocystic disease, cyst and fibroadenoma. In 21 cases out of the 41 cancer patients, the dual-energy subtraction radiography clearly visualized the malignant tumor shadows and the border of cancer infiltration and the daughter nodules by removing the shadows of normal mammary gland. On the other hand, benign diseases such as fibrocystic disease and cyst could be diagnosed as such, because the tumor shadow and the irregularly concentrated image of mammary gland disappeared by the dual-energy subtraction. These results suggest that this new technique will be useful in examination of breast masses.


Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays.
A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis. X-ray exposure (50 kVp) was defined to a 4.0 × 4.0 cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25-79 Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations. Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32 Gy with the central 2.0 × 2.0 cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs. The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI).


Electronic spectroscopy of nonalternant hydrocarbons inside helium nanodroplets.
We have recorded the electronic spectra of three polycyclic aromatic hydrocarbons (acenaphtylene, fluoranthene, and benzo(k)fluoranthene) containing a five-member ring and their van der Waals complexes with argon and oxygen with a molecular beam superfluid helium nanodroplet spectrometer. Although the molecules, which differ by addition of one or two fused benzene rings to acenaphtylene, have the same point group symmetry, the spectral lineshapes show distinct differences in the number of zero phonon lines and shapes of the phonon wings. Whereas the smallest molecule (acenaphtylene) has the most complicated line shape, the largest molecule (benzo(k)fluoranthene) shows different lineshapes for different vibronic transitions. The van der Waals complexes of fluoranthene exhibit more peaks than the theoretically allowed number of isomeric complexes with argon/oxygen. The current models of molecular solvation in liquid helium do not adequately explain these discrepancies.


Characterization of the chicken small intestine type IIb sodium phosphate cotransporter.
Intestinal absorption and renal resorption play a critical role in overall phosphorus homeostasis in chickens. Using RNase-ligase-mediated rapid amplification of cDNA ends PCR, we obtained a cDNA from the broiler small intestine that encodes a type IIb Na-dependent phosphate transporter. The cDNA has an open reading frame of 2,022 bp and predicts a 674-amino acid protein with a molecular mass of approximately 74 kDa. Prediction of membrane spanning domains based on the hydrophilic and hydrophobic properties of the amino acids suggests 8 transmembrane domains, with both the NH(2) and COOH termini being intracellular. The Na-inorganic phosphate (Pi) IIb cotransporter has relative high homology with other type II Na-Pi cotransporters but low homology with the type I or type III Na-Pi cotransporters. Northern blot analysis demonstrated the presence of a single mRNA transcript present predominantly in the small intestine, with the highest expression in the duodenum, followed by the jejunum and ileum. In situ hybridization indicated that the Na-Pi cotransporter mRNA is expressed throughout the vertical cryptvillus axis of the small intestine. Reduction of P in the diet of chicks from hatch to 4 d of age resulted in a significant induction of Na-Pi cotransporter mRNA expression in the small intestine. Further study is needed to elucidate its physiological role in intestinal phosphate absorption in chickens.


[Tracheoplasty for tracheal cuff stenosis post long-term tracheostomy].
We encountered a case of tracheal stenosis post tracheostomy, so-called cuff stenosis. A 43-year-old man with ventricular septal defect (VSD) was treated by oral endotracheal intubation because of heart-failure and pneumonia, and tracheostomy was performed. He was placed on artificial ventilation for almost 3 months. Four months after discharge, he complained of dyspnea and was treated by oral endotracheal intubation again. At that time bronchofiberscopy demonstrated severe circumferential stenosis of the trachea 4 cm from the tracheostomy spot and that was compatible with the cuff site. Although the stenotic portion was dilated by an endotracheal tube, 47-days after dilation, the portion was restenosed to almost 7 mm in diameter. Therefore, surgical treatment was necessary and tracheoplasty was performed by end-to-end suture after 2 cm (4 ring) resection of trachea. Tracheoplasty is the most reliable method of treating cuff stenosis after tracheostomy.


Vascular endothelial growth factor inhibits programmed cell death of endothelial cells induced by clinorotation.
The principal aim of this study was to investigate short- and long-term effects of clinorotation on human endothelial cells (EA hy 926 cell line) using a three-dimensional random positioning machine. Moreover, the impact of vascular endothelial growth factor (VEGF) was addressed. Immediately, within one hour and after four and twenty-four hours an increase of apoptotic cells was detected. VEGF significantly inhibited the amount of apoptotic endothelial cells (EC). VEGF reduced the amount of fas-positive EC. Moreover, after 24 hours, proliferating EC grew in form of three-dimensional multicellular spheroids and also as monolayers. The initially formed spheroids (maximum diameter 3 mm) remained stable up to the 15th day of clinorotation. Some spheroids revealed tubular structures. In addition, a clear increase of extracellular matrix proteins such as osteopontin and fibronectin was measured. The three-dimensional clinostat represents an important tool for cell biological experiments. VEGF significantly attenuated the changes of endothelial cells induced by simulated weightlessness in a cell protective manner.


Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria.
Animal models are essential to studies of infectious diseases. The use of mice to test bacterial infection has been extensively reported. However, methods applied to clinical isolates, particularly for carbapenem-resistant bacteria, must be tailored according to the infection models and bacteria used. In this study, we infected 6-week-old female BALB/c mice intraperitoneally with different strains of resistant bacteria plus 3% hog gastric mucin. This method was found to be efficient and readily applicable for investigation of carbapenem-resisant Gram-negative pathogens (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) detected in Korea.


Bronchiolitis obliterans associated with toxic epidermal necrolysis induced by infection: A case report and literature review.
Stevens-Johnson syndrome/toxic epidermal necrolysis has a severe impact on patients' eyes, genital mucosa, and many other organs. Bronchiolitis obliterans is a rare complication of Stevens-Johnson syndrome/toxic epidermal necrolysis. We report a case of bronchiolitis obliterans associated with toxic epidermal necrolysis in our department. Furthermore, we examined the patients with bronchiolitis obliterans induced by Stevens-Johnson syndrome/toxic epidermal necrolysis and summarized the clinical characteristics, treatment, and prognosis. Databases available online in English including PubMed, Medline, and Web of Science were consulted. We report one case and review 23 published case reports. Of the 24 patients, 13 were female, the oldest patient was 59 years old and the youngest was 5 years old. The time of bronchiolitis obliterans onset after Stevens-Johnson syndrome/toxic epidermal necrolysis varied from 5 days to 5 months. Bronchoscopy examination showed ulceration, exudative lesions, occlusion, and inflammation. The CT of lung manifestation included mosaic perfusion, bronchiectasis, consolidation, air trapping, pneumatocele, pleural thickening, lung collapse, larger central airway dilatation, lung overinflation, oligemia, and pneumomediastinum. Most cases indicated pulmonary function tests with obstructive ventilation dysfunction. The prognosis was poor; six of the patients died. Patients with Stevens-Johnson syndrome/toxic epidermal necrolysis may develop bronchitis obliterans at different stages, so all patients with Stevens-Johnson syndrome/toxic epidermal necrolysis should be followed up for possible respiratory complications.


A double-blind study of piretanide in the treatment of hypertension.
A double-blind trial was carried out in three parallel groups of patients with mild to moderate hypertension to assess the efficacy and tolerance of piretanide given as a single dose of 3 mg, 6 mg or 12 mg per day over a period of 12 weeks. Active drug treatment in the 90 patients studied was preceded and followed by 2-week periods on placebo. The results showed that although all three groups had significant reductions in systolic and diastolic blood pressures, both at rest and standing, compared with initial levels, the decrease was significantly greater in the two higher dosage groups. Pulse and respiratory rates also decreased and body weight was reduced slightly. The biochemical and haematological parameters in all three groups showed no clinically relevant changes during treatment with piretanide. Minor side-effects definitely or probably associated with piretanide treatment were observed in all three groups but were generally mild and did not interfere with treatment. Only 1 of the 9 patients who withdrew prematurely from the trial did so because of lack of effect, 1 patient withdrew because of side-effects and the other 6 patients who dropped out for drug-related reasons did so because the antihypertensive effects were too marked at the 6 mg (3 patients) or 12 mg (3 patients) per day dosage level.


The current role of laparoscopic surgery for gastroesophageal reflux disease in infants and children.
The benefits of surgery for gastroesophageal reflux disease (GERD) in infants and children have been questioned in the recent literature. The goal of this review was to determine the best current practice for the diagnosis and management of this disease. The literature was reviewed for all recent English language publications on the management of GERD in 8- to 10-year-old patients. In infants and children, GERD has multiple etiologies, and an understanding of these is important for determining which patients are the best surgical candidates. Proton pump inhibitors (PPIs) have become the mainstay of current treatment for primary GERD. Although laparoscopic surgery appears to be better than open surgery, there remains some morbidity and complications that careful patient selection can minimize. Surgery for GERD should be performed only after failure of medical management or for specific problems that mandate it.


Analysis of the relationship between community characteristics and depression using geographically weighted regression.
Achieving national health equity is currently a pressing issue. Large regional variations in the health determinants are observed. Depression, one of the most common mental disorders, has large variations in incidence among different populations, and thus must be regionally analyzed. The present study aimed at analyzing regional disparities in depressive symptoms and identifying the health determinants that require regional interventions. Using health indicators of depression in the Korea Community Health Survey 2011 and 2013, the Moran's I was calculated for each variable to assess spatial autocorrelation, and a validated geographically weighted regression analysis using ArcGIS version 10.1 of different domains: health behavior, morbidity, and the social and physical environments were created, and the final model included a combination of significant variables in these models. In the health behavior domain, the weekly breakfast intake frequency of 1-2 times was the most significantly correlated with depression in all regions, followed by exposure to secondhand smoke and the level of perceived stress in some regions. In the morbidity domain, the rate of lifetime diagnosis of myocardial infarction was the most significantly correlated with depression. In the social and physical environment domain, the trust environment within the local community was highly correlated with depression, showing that lower the level of trust, higher was the level of depression. A final model was constructed and analyzed using highly influential variables from each domain. The models were divided into two groups according to the significance of correlation of each variable with the experience of depression symptoms. The indicators of the regional health status are significantly associated with the incidence of depressive symptoms within a region. The significance of this correlation varied across regions.


Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells.
In this study, we first sought to determine the existence of side population (SP) cells in pancreatic cancer cell lines. Furthermore, we compared the biological characteristics of SP and non-SP cells. The presence of side population cells in pancreatic cancer cell lines was detected by Hoechst 33342 staining and FACS analysis. Cell cycle distribution was analyzed using flow cytometry. SP and non-SP cells were exposed to various concentrations of gemcitabine; drug sensitivity was examined using the MTT assay and flow cytometry using Annexin-V and PI staining. To compare the tumorigenic ability in vivo, groups of nude mice were orthotopically inoculated with varying numbers of SP and non-SP cells. The percentages of CD44+CD24+ and CD133+ in SP and non-SP cells were also detected by FACS analysis. The SP fraction was detected in BxPc-3, CFPAC-1, MIA PaCa-2, PANC-1 and SW1990 pancreatic cancer cell lines. Cell cycle analysis revealed that the SP cells contained more cells in the G1 phase and fewer cells in the S phase when compared with the non-SP cells. The SP cells exhibited increased tumorigenetic ability following in vivo transplantation into BALB/C nude mice and increased chemoresistance following in vitro exposure to gemcitabine. FACS analysis showed that the SP cells contained more CD44+CD24+ and CD133+ cells than the non-SP cells. In conclusion, these observations suggest that SP cells in the pancreatic cancer cell lines possess the property of cancer stem cells. SP cells may therefore be novel specific targets for the effective treatment of pancreatic cancer.


Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model.
Intimal hyperplasia (IH) is the substrate for accelerated atherosclerosis and limited patency of vein grafts. However, there is still no specific treatment targeting IH following graft surgery. In this study, we used a mouse model of vein grafting to investigate the potential for early intervention with platelet function for later development of graft IH. We transferred the inferior vena cava (IVC) from donor C57BL/6 mice to the carotid artery in recipients using a cuff technique. We found extensive endothelial injury and platelet adhesion one hour following grafting. Adhesion of leukocytes was distinct in areas of platelet adhesion. Platelet and leukocyte adhesion was strongly reduced in mice receiving a function-blocking antibody against the integrin αIIbβ3. This was followed by a reduction of IH one month following grafting. Depletion of platelets using antiserum also reduced IH at later time points. These findings indicate platelets as pivotal to leukocyte recruitment to the wall of vein grafts. In conclusion, the data also highlight early intervention of platelets and inflammation as potential treatment for later formation of IH and accelerated atherosclerosis following bypass surgery.


Sex-specific factors for bone density in patients with schizophrenia.
Patients with schizophrenia are susceptible to low bone mineral density (BMD). Many risk factors have been suggested. However, it remains uncertain whether the risk factors differ between men and women. In addition, the study of bone density in men is neglected more often than that in women. This study aims to examine specific risk factors of low BMD in different sexes. Men (n=80) and women (n=115) with schizophrenia, similar in demographic and clinical characteristics, were enrolled in three centers. Clinical and laboratory variables (including blood levels of prolactin, sex and thyroid hormones, cortisol, calcium, and alkaline phosphatase) were collected. BMD was measured using a dual-energy X-ray absorptiometer. Men had lower BMD than women. Predictors for BMD in men included hyperprolactinemia (B=-0.821, P=0.009), body weight (B=0.024, P=0.046), and Global Assessment of Functioning score (B=0.027, P=0.043); in women, BMD was associated with menopause (B=-1.070, P<0.001), body weight (B=0.027, P=0.003), and positive symptoms (B=0.094, P<0.001). In terms of the effect of psychotic symptoms, positive symptoms were related positively to BMD in women, but not in men. The findings suggest that sex-specific risk factors should be considered for an individualized intervention of bone loss in patients with schizophrenia. Physicians should pay particular attention to bone density in men with hyperprolactinemia and postmenopausal women. Further prospective studies in other populations are warranted to confirm these findings.


The feasibility of screening for abdominal aortic aneurysms in a district general hospital.
The feasibility of a screening programme for abdominal aortic aneurysms within a district general hospital population is explored, based on our current accepted knowledge of the natural history of this disease process. It is shown that ultrasound screening of males aged between 65 and 74 years, with elective repair of the aneurysms discovered, could save up to 20 lives per year in this district at a reasonable and justifiable cost. Moreover, such a programme would not place an unacceptable burden on existing radiological and surgical facilities.


Targeted agents: the rules of combination.
The success of molecularly targeted agents (MTA) in the treatment of cancer has led to the investigation of their use in combination with other MTAs and with conventional chemotherapies. An overview of the MTAs that have emerged as Food and Drug Administration-approved drugs is presented, along with a framework for the consideration of how MTAs can best be combined to maximize therapeutic effect.


A Review on the New and Old Anticoagulants.
Anticoagulants serve as the primary strategy for the prevention and treatment of both arterial and venous thromboembolism. Anticoagulants disrupt coagulation by interfering at various points in the coagulation cascade. This class of medications does not lyse clots that already exist; rather, it prevents thrombus formation and prevents or slows the extension of an existing clot. For decades, the standard therapy for patients requiring oral anticoagulation was warfarin. However, due to some of the shortcomings of warfarin, including the need for continuous routine monitoring, longtime onset and offset of anticoagulation effect, major food and drug interactions, and high incidence of bleeding, newer agents, termed direct oral anticoagulants, or DOACs were developed. This article will provide a review of clinically important information regarding the most commonly used anticoagulants and their reversal agents.


Sequential and parallel algorithms for DNA sequencing.
Reconstruction of the original DNA sequence in the sequencing by the hybridization approach (SBH) requires computational support due to a large number of possible combinations. One can notice a lack of algorithms admitting false-negative data and giving in addition all possible solutions. In this paper, a new method of sequencing has been proposed. An algorithm based on its idea (for the general case, when some data are missing, like in the real experiment) has been implemented and tested. Authentic DNA sequences have been used for testing. A parallel version of the algorithm has also been implemented and tested. The quality of the reconstruction is satisfactory for the library of oligonucleotides of length between 8 and 12, and 100, 200 and 300 bp long sequences. A way to a further decrease in the computation time is also suggested.


Cardiovascular flow measurement with phase-contrast MR imaging: basic facts and implementation.
Phase-contrast magnetic resonance (MR) imaging is a well-known but undervalued method of obtaining quantitative information on blood flow. Applications of this technique in cardiovascular MR imaging are expanding. According to the sequences available, phase-contrast measurement can be performed in a breath hold or during normal respiration. Prospective as well as retrospective gating techniques can be used. Common errors in phase-contrast imaging include mismatched encoding velocity, deviation of the imaging plane, inadequate temporal resolution, inadequate spatial resolution, accelerated flow and spatial misregistration, and phase offset errors. Flow measurements are most precise if the imaging plane is perpendicular to the vessel of interest and flow encoding is set to through-plane flow. The sequence should be repeated at least once, with a high encoding velocity used initially. If peak velocity has to be estimated, flow measurement is repeated with an adapted encoding velocity. The overall error of a phase-contrast flow measurement comprises errors during prescription as well as errors that occur during image analysis of the flow data. With phase-contrast imaging, the overall error in flow measurement can be reduced to less than 10%, an acceptable level of error for routine clinical use.


Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy.
To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy (BNSRRP) and possible effect of Tadalafil. A total of 65 patients underwent BNSRRP and they were evaluated prospectively for a whole year of follow-up. The patients were randomized to control without rehabilitation (Group 1) or Tadalafil rehabilitation group (Group 2). The patients were evaluated at months 3, 6 and 12 postoperatively for erectile function, penile measurements (flaccid penile length, penile length at maximum erection, penile circumference at flaccid status, and penile circumference at maximum erection), penile abnormalities and general health status. Statistical analysis was performed by Chi-Square test and significance was defined as p value < 0.05. In Group 1 there was significant decrease in penile measurements at month 3 compared to preoperative measurements. There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant. There were no significant differences between postoperative months 6 and 12 for all measurements. In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline. There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year. Although further large sampled trials are needed to describe the possible positive effect of tadalafil or other PDE5-I 's on penile size after BNSRRP, tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP.


Biogenesis of epithelial cell plasma membranes.
Polarized monolayers of cultured epithelial cells, such as the kidney-derived MDCK cell line, when infected with enveloped viruses, provide a convenient model system for study of the intracellular routes followed by newly synthesized glycoproteins to reach specific domains of the plasma membrane. The polarized nature of the monolayers is reflected in the asymmetric assembly of enveloped viruses, some of which, such as influenza and simian virus 5 (SV5), bud from the apical surfaces of the cells, while others, such as vesicular stomatitis virus (VSV), emerge from the basolateral surfaces. MDCK cells can sustain double infection with viruses of different budding polarity, and within such cells the envelope glycoproteins of the two viruses are synthesized simultaneously and assembled into virions at different sites. Immunoelectron microscopic observations of doubly infected cells show that glycoproteins of influenza and VSV traverse the same Golgi apparatus. This indicates that critical sorting steps must take place during or after passage of the glycoproteins through the organelle. Following passage through the Golgi, the HA glycoprotein accumulates almost exclusively at the apical surface, where the influenza virions assemble. Significant amounts of the G protein, however, are detected on both plasma membranes in singly and doubly infected cells, although VSV virion assembly is limited to basolateral domains. These observations indicate that the site of VSV budding is not exclusively determined by the presence of G polypeptides on a given cell-surface domain. It is possible that other cellular or viral components are responsible for the selection of the appropriate budding domain or that the G protein found on the apical surface must be transferred to the basolateral domain before it becomes competent for assembly.


Whole-Genome Sequencing and Target Validation Analysis of Müllerian Adenosarcoma: A Tumor With Complex but Specific Genetic Alterations.
Mullerian adenosarcoma (MAS) is a biphasic tumor with malignant stroma. It is most commonly of endometrial origin but occasionally originates in the cervix, ovary, or other pelvic/peritoneal sites. The typical MAS is low grade with an indolent clinical course; however, tumors with sarcomatous overgrowth (SO) or a high-grade sarcoma tend to be aggressive. Tumor etiology is largely unknown. To better understand the global genome alterations and gene mutations in MAS, whole-genome sequencing (WGS) and target validation analysis were performed. MAS showed remarkable chromosome (chr) copy number variation (CNV), specifically, gains in chr 1q, 5p, 12p, 12q, and 17q and losses in chr 3p, 3q, 9p, and 11q. Gain of chr 12q13-15 was present in 50% of cases. The selected gene products in gain regions were upregulated as measured by immunohistochemistry. HMGA2 overexpression was significantly correlated with SO. While the structural variation (SV) rate was relatively low overall, a disproportionally high rate of break-ends at chr 7 was noted involving 6 in-frame rearrangement fusion genes. Among 40 frequently mutated genes detected by WGS and validated in 29 MAS by next generation sequencing (NGS), KMT2C, and BCOR were frequently seen in MAS both with and without SO, while MAGEC1 and KDM6B were strongly associated with SO. Overall, a higher rate of frequently mutated genes was found in MAS with SO (33%) than MAS without (11%). This study uncovers the complex and specific genetic alterations in this malignancy. The findings provide a tool for future investigation of these molecular changes in tumorigenesis and target therapies.


Do 'auditory processing' tests measure auditory processing in the elderly?
To examine the associations between measures of auditory processing and measures of auditory or cognitive function in elderly listeners with impaired hearing. Multiple measures of auditory processing, auditory function, and cognitive function were obtained and linear, multiple-regression analyses were conducted to examine the relations between these sets of variables. In particular, four measures of auditory processing were obtained from each of 213 elderly participants. Measures of auditory processing included duration discrimination for a 1000-Hz pure tone, temporal-order discrimination for mid-frequency pure tones, dichotic syllable identification, and recognition of 45% time-compressed monosyllables. Each participant also completed additional measures of auditory function, including pure-tone thresholds, auditory brain stem responses for each ear and at two presentation rates (11.1 and 71.1 clicks per second), and performance-intensity functions for monosyllabic words (PI-PB rollover). Finally, three measures of cognitive function, all from the Wechsler Adult Intelligence Scale-Revised, were obtained from the 213 participants. For three of the four measures of auditory processing examined in this study (duration discrimination, temporal-order discrimination, and dichotic CV identification), a measure of cognitive function (IQ) and age were the two primary predictors of individual differences in performance. For these three measures of auditory processing, 11 to 14% of the total variance could be accounted for by the predictor variables. For the remaining measure of auditory processing (recognition of time-compressed monosyllables), 56% of the total variance could be accounted for by a set of four predictor variables, but most of this variance (54% of the total variance) was associated with individual differences in hearing loss. When hearing loss was removed as a predictor for this measure of auditory processing, 14% of the total variance was explained by four variables: age, IQ, and two measures derived from auditory brain stem response wave-V latency. Performance on the battery of auditory processing measures by elderly hearing-impaired listeners was systematically related to individual differences in cognitive function rather than auditory function, especially for stimuli not affected by peripheral hearing loss. However, much of the variance in auditory processing performance remained unaccounted for by any of the predictor variables examined in this study.


Computer-assisted surgery in the frontal and maxillary sinus.
We report the intraoperative use of bent probes for 3-dimensional computer-assisted navigation in ENT surgery with the ISG Viewing Wand. Probe calibration is standardized and the new probes comply with the overall application accuracy of the navigation system. The bent probes permit an easy access to the remotest locations of the maxillary and the frontal sinus and are beneficial for application in paranasal sinus surgery. We present our clinical experiences with these probes.


Minimally invasive maxillary sinus elevation using balloon system: A case series.
The posterior maxillary segment frequently exhibits insufficient bone mass to support dental implants. Sinus floor augmentation enables implant placement in the posterior maxilla. This case series included ten sites, in which sinus floor elevation was done using sinus lift balloon system followed by augmentation utilizing irradiated cancellous bone allograft. Postoperative radiographic assessment of vertical bone gain was done at 3 and 6 months follow-up period. The mean initial and final bone height were 6.16 and 10.50 mm, respectively, with a mean increase of 4.34 mm at 6 months being observed with nil complication. The presented technique might represent a viable alternative for sinus elevation in posterior atrophied maxilla. Irradiated cancellous bone allograft can be advocated as an ideal bone graft material for sinus augmentation procedures.


Loading Patterns of Rubber-Based Resistance Bands across Distributors.
Variable resistance implemented through concurrent use of rubber-based resistance bands and free weights is commonly used in training athletes. The purpose of this study was to examine the consistency of rubber-based resistance (RBR) band loading patterns across four distributors. Bands (n = 141) were obtained from online distributors (Rogue Fitness, EliteFTS, RubberBanditz, and Power Systems) across a spectrum of available widths (0.635, 1.270, 2.860, 4.450, 6.350, and 10.160 cm). At least five bands for each width were stretched in 5 cm increments from resting (100 cm) to twice resting length (200 cm) while tensile resistance was measured using a load cell integrated with a digital controller. Each band was tested twice on non-consecutive days producing an intertrial intraclass correlational coefficient (ICC) between 0.93⁻0.99 with a grand mean ICC across all repeated measures of 0.99. Statistical differences were observed in mean resistance for bands of equal thickness across distributors. Significant correlations were found between a range of tensile load expressed as a total load and band thickness (r = 0.658) and when expressed as a percentage (r = -0.386). This study is useful for strength and conditioning professionals and clinicians who should be cognizant of loading variability within both bandwidths and between distributors.


Infected symptomatic carotid artery atheroma concurrent with bacterial endocarditis.
Optimal management of patients with stroke due to symptomatic carotid artery disease coexistent with bacterial endocarditis is still not well established. We report the case of a patient who presented with multifocal left middle cerebral artery stroke in the setting of Enterococcus faecalis endocarditis and was found to have near-occlusive ipsilateral carotid artery stenosis in stroke workup. Carotid artery endarterectomy was performed, and atheroma material demonstrated complicated plaque with cultures positive for E. faecalis This report demonstrates that patients with cardioembolic disorders such as bacterial endocarditis with vegetations who present with stroke may benefit from evaluation for extracranial vessel stenosis. Also, additional consideration should be given to the possibility of infected atheroma in patients with symptomatic carotid stenosis with recent or active endocarditis or bacteraemia.


Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure.
A rat model of third trimester fetal alcohol exposure was used to determine whether a smaller daily dose of alcohol can induce more severe microencephaly and neuronal loss than a larger dose, if the small dose is consumed in such a way that it produces higher blood alcohol concentrations (BACs). The possibility of regional differences within the developing brain to alcohol-induced neuronal loss was also investigated. Sprague-Dawley rat pups were reared artificially over postnatal Days 4-10 (a period of rapid brain growth similar to that of the human third trimester). Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 5.1% solution in four of the 12 daily feedings or as a 10.2% solution in two of the 12 feedings. A third group received a higher daily dose (6.6 g/kg) administered as a 2.5% solution in every feeding. Gastrostomy and suckle controls were also reared. On postnatal Day 10, the animals were perfused, and brain weights were obtained. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. In the cerebellum, Purkinje cells and granule cells were counted in each of the ten lobules of the vermis. The lower daily dose (4.5 g/kg) condensed into two or four feedings produced high maximum BACs (means of 361.6 and 190.7 mg/dl, respectively) and significant microencephaly and cell loss, relative to controls. The higher daily dose (6.6 g/kg), administered continuously, resulted in low BACs (mean of 39.2 mg/dl) and induced no microencephaly or cell loss. Regional differences in neuronal vulnerability to alcohol were evident. In the hippocampus, CA1 neuronal number was significantly reduced only by the most condensed alcohol treatment, while CA3, CA4, and the dentate gyrus populations were not reduced with any alcohol treatment. In the cerebellum, some lobules suffered significantly greater Purkinje cell loss and granule cell loss than did others. The regions in which Purkinje cells were most mature at the time of the alcohol exposure were the most vulnerable to Purkinje cell loss.


[Construction of Plasmodium falciparum signal peptide peptidase-GFP mutant and its expression analysis in the malaria parasite].
To construct recombinant plasmid pSPPcGT which contains signal peptide peptidase gene of Plasmodium falciparum (PJSPP) and GFP, and transfect into P. falciparum (3D7 strain) to obtain mutant parasites which can express PJSPP-GFP. Plasmodium falciparum(3D7 strain) genomic DNA was extracted from cultured malaria parasites. The C-terminal region of PJSPP, an 883 bp gene fragment was amplified by PCR, and then cloned into pPM2GT vector to get recombinant vector pSPPcGT. The recombinant vectors were identified by PCR, double restriction enzyme digestion and DNA sequencing. pSPPcGT vector was transfected into malaria parasites. The positive clones were selected by adding inhibitor of Plasmodium falciparum dihydrofolate reductase WR99210 to the culture medium. The pSPP-GFP-transfected parasites were fixed with methanol, stained with DAPI, and observed under immunofluorescence microscope. The PJSPP-GFP expression in P. falciparum was identified by SDS-PAGE and Western blotting. The C-terminal region of PJSPP was amplified from P.falciparum (3D7 strain) genomic DNA by PCR with the length of 883 bp. The constructed recombinant vectors were identified by PCR screening, double restriction enzyme digestion and DNA sequencing. The pSPPcGT vector was transfected into P. falciparum and the positive clones were selected by WR99210. GFP fluorescence was observed in transfected parasites by immunofluorescence microscopy, and mainly located in the cytoplasm. The PJSPP-GFP expression in malaria parasites was confirmed by Western blotting with a relative molecular mass of Mr 64,000. Recombinant vector PJSPP-GFP is constructed and transfected into P. falciparum to obtain P. falciparum mutant clone which can express PfSPP-GFP.


Nanoparticles fabricated from the bioactive tilapia scale collagen for wound healing: Experimental approach.
The creation of innovative wound-healing nanomaterials based on natural compounds emerges as a top research goal. This research aimed to create a gel containing collagen nanoparticles and evaluate its therapeutic potential for skin lesions. Collagen nanoparticles were produced from fish scales using desolvation techniques. Using SDS PAGE electrophoresis, Fourier transform infrared spectroscopy (FTIR) as well as the structure of the isolated collagen and its similarities to collagen type 1 were identified. The surface morphology of the isolated collagen and its reformulation into nanoparticles were examined using transmission and scanning electron microscopy. A Zeta sizer was used to examine the size, zeta potential, and distribution of the synthesized collagen nanoparticles. The cytotoxicity of the nanomaterials was investigated and an experimental model was used to evaluate the wound healing capability. The overall collagen output from Tilapia fish scales was 42%. Electrophoretic patterns revealed that the isolated collagen included a unique protein with chain bands of 126-132 kDa and an elevated beta band of 255 kDa. When compared to the isolated collagen, the collagen nanoparticles' FTIR results revealed a significant drop in the amide II (42% decrease) and amide III (32% decrease) band intensities. According to SEM analysis, the generated collagen nanoparticles ranged in size from 100 to 350 nm, with an average diameter of 182 nm determined by the zeta sizer. The produced collagen nanoparticles were polydispersed in nature and had an equivalent average zeta potential of -17.7 mV. Cytotoxicity study showed that, when treating fibroblast cells with collagen nanoparticle concentrations, very mild morphological alterations were detected after human skin fibroblasts were treated with collagen nanoparticles 32 μg/ml for 24 hours, as higher concentrations of collagen nanoparticles caused cell detachment. Macroscopical and histological investigations proved that the fabricated fish scale collagen nanoparticles promoted the healing process in comparison to the saline group.


The challenges of purpose in the face of chaos: commentary paper by Professor Beverley Raphael.
This paper addresses the issues and purposes of psychiatric research into disaster. Purposes include those that are focused on basic scientific questions, such as the role of disaster stressors in contributing to the development of psychiatric morbidity, and research attempting to identify the level of mental health need. There is also intervention research but this is limited in the acute emergency and longer term. These questions and the methodologies to address them, overlap significantly. Many studies use different measures of exposure, disorder and other disaster variables. There is also a wide range of population groups studied, making comparison of findings difficult. Thus, for these large scale events affecting populations, studies may not readily meet either the purposes of affected populations or government funders. Nor are interventions systematically operationalized to promoted replication. Challenges lie in the diversity of researchers, the pluralistic nature of Western society and the rapid development of the field. It is suggested that a set of disaster mental health research standards, based on core principles and data, would facilitate national and international collaboration and the interests of individual researcher. This could lead to comparable studies that could progress the field, while at the same time fostering innovations which could link to these research programmes. Strategic partnerships with government and other funders, as well as affected communities, could strengthen advocacy and commitment for disaster mental health research.


Examining the relationship between post-traumatic stress disorder and social participation among Veterans with spinal cord injuries and disorders.
The objectives of this study were to examine differences in social participation among Veterans with spinal cord injuries/disorders with and without post-traumatic stress disorder, and determine if lower social participation was independently associated with having post-traumatic stress disorder. A cross-sectional mailed national survey was sent to a national sample of Veterans with spinal cord injuries/disorders who received prior-year Veterans Affairs healthcare. Surveys provided data on: demographics, health conditions, injury characteristics, and social participation. Analyses included bivariate comparisons, and multivariate logistic regression to determine if lower social participation was independently associated with post-traumatic stress disorder. Veterans with (vs. without) post-traumatic stress disorder (n = 896) reported lower social participation (40.2 vs. 43.9, p < 0.0001). Multivariate analyses showed that longer duration of injury (OR = 0.98, 95% CI: 0.97-1.00, p = 0.04) and white race (OR = 0.62, 95% CI: 0.38-1.01, p = 0.05) were associated with lower odds of post-traumatic stress disorder, while a greater number of health conditions (OR = 1.43, 95% CI: 1.25-1.64, p < 0.0001) was associated with greater odds. When controlling for covariates, lower social participation was independently associated with post-traumatic stress disorder (OR = 0.94, 95% CI: 0.90-0.98, p = 0.003). Results indicate post-traumatic stress disorder is associated with lower social participation in Veterans with spinal cord injuries/disorders, independent of other factors that may impact participation. Efforts to screen for and treat post-traumatic stress disorder among persons with spinal cord injuries/disorders, regardless of injury-specific factors, are needed to improve participation. Implications for Rehabilitation Individuals with spinal cord injuries/disorders often have post-traumatic stress disorder; in Veterans with spinal cord injuries/disorders this may be compounded by trauma incurred through military experiences. Social participation, an important aspect of rehabilitation and community integration following spinal cord injury or disorder, may be hindered by symptoms of post-traumatic stress disorder. Our data show that post-traumatic stress disorder is associated with lower social participation in Veterans with spinal cord injuries/disorders, independent of other factors that may impact participation. These results indicate that efforts to screen for and treat post-traumatic stress disorder among persons with spinal cord injuries/disorders, regardless of injury-specific factors, are needed to improve participation in this patient population.


White matter alterations in Williams syndrome related to behavioral and motor impairments.
Myelin is the electrical insulator surrounding the neuronal axon that makes up the white matter (WM) of the brain. It helps increase axonal conduction velocity (CV) by inducing saltatory conduction. Damage to the myelin sheath and WM is associated with many neurological and psychiatric disorders. Decreasing myelin deficits, and thus improving axonal conduction, has the potential to serve as a therapeutic mechanism for reducing the severity of some of these disorders. Myelin deficits have been previously linked to abnormalities in social behavior, suggesting an interplay between brain connectivity and sociability. This review focuses on Williams syndrome (WS), a genetic disorder characterized by neurocognitive characteristics and motor abnormalities, mainly known for its hypersociability characteristic. We discuss fundamental aspects of WM in WS and how its alterations can affect motor abilities and social behavior. Overall, findings regarding changes in myelin genes and alterations in WM structure in WS suggest new targets for drug therapy aimed at improving conduction properties and altering brain-activity synchronization in this disorder.


An "unavoidable" death in a people's marathon.
With the increase in jogging and distance running as a means of attaining and maintaining fitness, and in the light of the difficulty in advising certain groups of patients about their capacity for such exercise, we report on several potentially avoidable factors in the death of a 45 year old Sheffield Marathon runner in June 1983.


Monoaminergic modulation of GABAergic transmission onto cerebellar globular cells.
Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells. Application of either serotonin (5-HT) or noradrenaline (NA) excited globular cells, thereby leading to their firing. The 5-HT- and NA-induced firing was temporally confined and attenuated by GABAergic transmission, although 5-HT and NA exerted an inhibitory effect on the release of GABA from presynaptic terminals of PC axon collaterals. Agonists for 5-HT1B receptors and α2-adrenoceptors mimicked the 5-HT- and NA-induced suppression of GABAergic activity. Through their differential modulatory actions on the cerebellar inhibitory neural circuits, 5-HT facilitated PC firing, whereas NA suppressed it. These results indicate that 5-HT and NA regulate the membrane excitability of globular cells and PCs through their differential modulation of not only the membrane potential but also GABAergic synaptic circuits. Monoaminergic modulation of the neural connections between globular cells and PCs could play a role in cerebellar motor coordination.


Role of Type 2 NAD(P)H Dehydrogenase NdbC in Redox Regulation of Carbon Allocation in Synechocystis.
NAD(P)H dehydrogenases comprise type 1 (NDH-1) and type 2 (NDH-2s) enzymes. Even though the NDH-1 complex is a well-characterized protein complex in the thylakoid membrane of Synechocystis sp. PCC 6803 (hereafter Synechocystis), the exact roles of different NDH-2s remain poorly understood. To elucidate this question, we studied the function of NdbC, one of the three NDH-2s in Synechocystis, by constructing a deletion mutant (ΔndbC) for a corresponding protein and submitting the mutant to physiological and biochemical characterization as well as to comprehensive proteomics analysis. We demonstrate that the deletion of NdbC, localized to the plasma membrane, affects several metabolic pathways in Synechocystis in autotrophic growth conditions without prominent effects on photosynthesis. Foremost, the deletion of NdbC leads, directly or indirectly, to compromised sugar catabolism, to glycogen accumulation, and to distorted cell division. Deficiencies in several sugar catabolic routes were supported by severe retardation of growth of the ΔndbC mutant under light-activated heterotrophic growth conditions but not under mixotrophy. Thus, NdbC has a significant function in regulating carbon allocation between storage and the biosynthesis pathways. In addition, the deletion of NdbC increases the amount of cyclic electron transfer, possibly via the NDH-12 complex, and decreases the expression of several transporters in ambient CO2 growth conditions.


The diabetic foot: epidemiology.
The epidemiology of the diabetic foot is still unknown because this heterogeneous pathologic condition is non uniformly classified and described. Lower limb peripheral vascular disease has a preferential distal location strongly associated with the classical factors of cardiovascular risk. Ulcers occur in 15% of diabetics and 6-20% of all hospitalized diabetic patients are affected by ulcers of the foot. There is a predictive feature of the severity of the ulcer in relation to its location. In the USA, ischemia-related amputations are about 200 per million per year for non diabetics as against 3900 per million for diabetics; furthermore the incidence of a second amputation rises to 51% 5 years after first amputation. Risk factors for amputation are: smoking, hypertension, dyslipidemia, elderly age, glycosylated hemoglobin levels. Although mortality has decreased in the last 50 years, the diabetic foot is still a huge economic problem.


Long-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicin.
Incidence of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected persons has dramatically decreased in the highly active antiretroviral therapy era. However, this tumor still represents the most common cancer in this population. The objectives of this study were to evaluate long-term prognosis of HIV-infected patients with KS who had received pegylated liposomal doxorubicin (PLD) and, more specifically, to assess tumor relapse rate, mortality, and cause of death in these subjects. This study was a retrospective review of all patients with KS who had received PLD in centers belonging to the Caelyx/KS Spanish Group. Kaplan-Meier analysis and univariate and multivariate Cox-regression analysis were used to assess the rate of and factors associated with relapse and death through January 2006. A total of 98 patients received PLD from September 1997 through June 2002. Median follow-up after initiation of treatment was 28.7 months (interquartile range, 6.6-73.2 months); during follow-up, 29 patients died (a mortality rate of 14.6% per year). In 9 patients (31%), the cause of death was related to the appearance of other tumors (including 7 lymphomas, 1 gastrointestinal adenocarcinoma, and 1 tongue epidermoid cancer). Death caused by progression of KS occurred in 3 cases. Death risk was inversely related to CD4(+) cell counts at the end of follow-up (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.5-0.9). A relapse study was performed for 61 patients who had complete or partial response to PLD and who attended a control visit after treatment completion. After a median follow-up of 50 months (interquartile range, 17.2-76 months), 8 patients (13%) had experienced relapse; 5 of these patient experienced relapse within the first year after stopping PLD. The only factor that was independently related to risk of relapse was having a CD4(+) cell count >200 cells/microL at baseline (hazard ratio, 6.2; 95% confidence interval, 1.2-30). Lower CD4(+) cell count at the end of follow-up was marginally associated with relapse (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.6-1.01). Treatment of KS with PLD in HIV-infected patients is followed by a low relapse rate, with most relapses occurring during the first year after stopping chemotherapy. However, the mortality rate in this population was high, in part because of an unexpectedly high incidence of other tumors, mainly lymphomas.


Changes in laryngeal muscle activities during hypercapnia in the cat.
The larynx has three functions: phonation, airway protection, and respiration. Few studies have dealt with laryngeal respiratory function. To elucidate respiratory regulation by the larynx, we studied the changes in the activity of the intrinsic laryngeal muscles during hypercapnia in decerebrated cats. The electromyographic activities of the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded simultaneously with an electromyogram of the diaphragm, endotracheal pressure, and concentrations of O2 and CO2. The activity of the intrinsic laryngeal muscles during hypercapnia (end-tidal CO2, 8% to 10%) was analyzed in comparison with that during eucapnia. In hypercapnia, both the PCA and TA muscles increased their activities, and the endotracheal pressure during expiration was elevated to a higher level than that in eucapnia. TA muscle activities returned to the level during eucapnia after ligation of the common carotid arteries. These findings suggest that hypercapnia causes a further widening of the glottis during inspiration to decrease inspiratory resistance and a further narrowing of the glottis during expiration to prevent alveolar collapse. Thus it may be concluded that the larynx actively participates in respiratory regulation under the control of the brain stem through a process of peripheral inputs from the carotid receptors.


Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described inherited disorder. The pathologic gene maps on chromosome 19. The clinical spectrum of the disease consists of recurrent strokes, migraine, transient ischemic attacks, mood changes, and dementia. We report a genetically assessed CADASIL family with atypical clinical presentations of epileptic seizures. In two asymptomatic family members there were early brain abnormalities on MRI. Our report expands the clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed disorder.


Carboxylate and amino group coated silver nanoparticles as joining materials for copper-to-copper silver joints.
Organic silver complexes are introduced where silver is linked either with a carboxyl group or with an amino group. Upon heating, nanoparticles are generated if the respective ligands are long enough to act as stabilizing agents in the nanoparticulate regime. With decomposition and volatilization of the organic material, the sintering of silver occurs. The thermal characteristics of the carboxylates silver-n-octanoate, silver-n-decanoate, and AgOOC(CH2OCH2)2CH2OCH3 are compared with silver-n-alkylamines (n = 8, 9, and 12), and their thermal behavior is discussed based on thermogravimetry (TG) measurements. The consecutive stages of a metallization process are addressed based on the properties of AgOOC(CH2OCH2)2CH2OCH3, and the usable effects of the individual phases of this metal organic compound are analyzed by cross-sectional scanning electron microscope (SEM) images of silver joints. Selection criteria are addressed based on the thermal behavior. A mechanism for the joining process is proposed, considering formation and sintering of the nanoparticles. It was found that the bulk material can be used for low-temperature joining processes. Strong adherence to copper as a basic material can be achieved.


Secondary angiosarcoma following irradiation--case report and review of the literature.
Angiosarcoma is a rare malignant tumor that accounts for 1% to 2% of all soft tissue sarcomas. This paper reports a case of radiation-associated angiosarcoma with a literature review of 66 cases. Twenty-nine years after transabdominal hysterectomy and adjuvant radiation therapy for uterine cervix cancer, cutaneous angiosarcoma developed in the abdominal wall of a 63-year-old woman. She underwent wide excision of the abdominal wall mass, radiation therapy, and chemotherapy, and has been alive and well without any evidence of metastasis for 23 months since the initial diagnosis of angiosarcoma. After an intensive literature review, we found 66 cases of radiation-associated angiosarcoma. The most common primary disease was breast cancer (44%), with gynecologic cancer (21%) next. Eighty-five percent of radiation-associated angiosarcomas developed in the cutaneous area. The median age at diagnosis was 65 years, and the median latency period from irradiation to diagnosis was 96 months. The median survival period of 48 patients whose survival lengths could be reviewed was 12 months.


Direct Drawing Method of Graphite onto Paper for High-Performance Flexible Electrochemical Sensors.
A simple and fast fabrication method to create high-performance pencil-drawn electrochemical sensors is reported for the first time. The sluggish electron transfer observed on bare pencil-drawn surfaces was enhanced using two electrochemical steps: first oxidizing the surface and then reducing it in a subsequent step. The heterogeneous rate constant was found to be 5.1 × 10-3 cm s-1, which is the highest value reported so far for pencil-drawn surfaces. We mapped the origin of such performance by atomic force microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Our results suggest that the oxidation process leads to chemical and structural transformations on the electrode surface. As a proof-of-concept, we modified the pencil-drawn surface with Meldola's blue to electrocatalytically detect nicotinamide adenine dinucleotide (NADH). The electrochemical device exhibited the highest catalytic constant (1.7 × 105 L mol-1 s-1) and the lowest detection potential for NADH reported so far in paper-based electrodes.


Structural determination and daily variations of porcine milk oligosaccharides.
Free milk oligosaccharides (OS) are major components of mammalian milk. Swine are important agricultural species and biomedical models. Despite their importance, little is known of the OS profile of porcine milk. Herein, the porcine milk glycome was elucidated and monitored over the entire lactation period by liquid chromatography profiling and structural determination with mass spectrometry. Milk was collected from second-parity sows (n = 3) at farrowing and on days 1, 4, 7, and 24 of lactation. Twenty-nine distinct porcine milk oligosaccharides (pMO) were identified. The pMO are highly sialylated, which is more similar to bovine milk than human milk OS. Six fucosylated pMO were detected at low levels in porcine milk, making it more similar to human milk than bovine milk. In general, the pMO content was highest in milk collected at farrowing and day 1 of lactation, decreased during early lactation, but then rose at day 24; however, the pMO displayed different patterns of variation across lactation. In summary, porcine milk contains both acidic (sialylated) and neutral OS, but sialic acid containing OS predominate throughout lactation.


Putative G protein-coupled receptors in parasitic nematodes--potential targets for the new anthelmintic class cyclooctadepsipeptides?
Parasitic nematodes cause major problems in livestock animals. Resistances to the most commonly used drugs are arising. The cyclooctadepsipeptide emodepside belongs to a new class of anthelmintics. A receptor for emodepside, Hc110-R, was previously identified in Haemonchus contortus. We have identified the complete coding sequences of putative orthologues in Cooperia oncophora and Ostertagia ostertagi, tri-chostrongyles in cattle. The putative receptors were named depsiphilins. The deduced amino acid sequence of C. oncophora depsiphilin has a similarity of 91% to the O. ostertagi sequence. The similarity of both the C. oncophora and O. ostertagi depsiphilin to Hc110-R is 89%, based on the amino acid sequence. The depsiphilins share 46% identity with the latrophilin-like protein 1 in Caenorhabditis elegans and 47% identity with a hypothetical protein in Caenorhabditis briggsae. Hc110-R and the latrophilin-like proteins of C. elegans were previously reported to be putative G protein-coupled receptors (GPCRs) and to be related to mammalian latrophilins. A seven transmembrane domain, a GPCR proteolytic site, and other conserved domains characteristic of receptors of the latrophilin group were identified within the depsiphilins. Therefore it seems reasonable to allocate the depsiphilins to the previously described latrophilins and latrophilin-like proteins.


SPOt: A novel and streamlined microarray platform for observing cellular tRNA levels.
Recent studies have placed transfer RNA (tRNA), a housekeeping molecule, in the heart of fundamental cellular processes such as embryonic development and tumor progression. Such discoveries were contingent on the concomitant development of methods able to deliver high-quality tRNA profiles. The present study describes the proof of concept obtained in Escherichia coli (E. coli) for an original tRNA analysis platform named SPOt (Streamlined Platform for Observing tRNA). This approach comprises three steps. First, E. coli cultures are spiked with radioactive orthophosphate; second, labeled total RNAs are trizol-extracted; third, RNA samples are hybridized on in-house printed microarrays and spot signals, the proxy for tRNA levels, are quantified by phosphorimaging. Features such as reproducibility and specificity were assessed using several tRNA subpopulations. Dynamic range and sensitivity were evaluated by overexpressing specific tRNA species. SPOt does not require any amplification or post-extraction labeling and can be adapted to any organism. It is modular and easily streamlined with popular techniques such as polysome fractionation to profile tRNAs interacting with ribosomes and actively engaged in translation. The biological relevance of these data is discussed in regards to codon usage, tRNA gene copy number, and position on the genome.


Self-Perception and the Relation to Actual Driving Abilities for Individuals With Visual Field Loss.
In Sweden, individuals with visual field loss (VFL) have their driving license withdrawn. The literature clearly indicates that individuals with VFL are unsafe drivers on a group level. However, many drivers with VFL can be safe on an individual level. The literature also suggests that self-perception, beliefs, and insights of one's own capabilities are related to driving performance. This study had three aims: (1) To investigate self-perceived driving capability ratings for individuals with VFL; (2) to compare these ratings between groups with different medical conditions associated with VFL (stroke, glaucoma, and diabetes); and (3) to relate the self-perception ratings to actual driving performance in an advanced driving simulator. Participants comprised 723 individuals whose driver's license had been withdrawn because of VFL and 92 normally sighted elderly individuals. All participants completed a background survey, rated difficulties with different traffic situations, rated their strengths and weaknesses as drivers, and rated aspects that were important for causing traffic accidents. Of the VFL group participants, 264 also completed a simulator-based driving test that they knew could lead to renewal of their driving license. VFL participants and normally sighted was at the same age when they completed the simulator driving test. Overall, individuals with VFL rated their capabilities as high on all instruments and scales used, even higher than the elderly normally sighted control group. The only VFL etiology group that rated lower than other groups was the diabetes group. Safety orientation and internal control orientation values were best at discriminating between VFL participants in terms of self-perception of driving performance. Participants categorized as "high" in terms of safety skills and internal control were more modest in their ratings. Finally, participants who passed the simulated driving test did not differ from those who failed, in any of the self-perception measures. Self-perception ratings among individuals with VFL were higher than those of normally sighted elderly individuals. Self-assessed skills did not predict driving performance. Groups with different VFL etiologies rated similarly. Self-ratings of driving abilities cannot be used to assess actual driving performance. Actual driving tests (on road or in the simulator) are necessary to discriminate between safe and unsafe drivers with VFL.


Synthesis of azapolycyclic systems via the intramolecular [4 + 2] cycloaddition chemistry of 2-(alkylthio)-5-amidofurans.
A series of 2-(methylthio)-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) with beta-alkoxy-gamma-dithiane amides 13-16 and 27-32 in 40-70% yield. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). With the exception of 45 and 46, the oxa-bridged cycloadducts could not be isolated but immediately underwent a 1,2-methylthio shift to form bicyclic lactams in 60-100% yield. It was determined that incorporation of the amido carbonyl in the tether allowed the IMDAF reaction to proceed at a lower temperature. A dramatic example of this is seen in the IMDAF reaction of furan 35, in which the presence of an amido carbonyl as part of the dienophile tether, as opposed to the annealed ring (66) or the lack of a carbonyl (67), was necessary for the cycloaddition to occur. Furan 37, annealed to an azepine ring, underwent the IMDAF reaction at or below room temperature. To identify structural features that promote the IMDAF reaction, a computational study was undertaken. Ground-state and transition-state energies were calculated for furans 17, 33, 37, and 64 using the Becke 3LYP/6-31G model. The theoretical results were in good agreement with those observed. The results indicate that the incorporation of an amide carbonyl as part of the tether system works to place the dienophile in closer proximity to the furan ring, thereby lowering the activation energy needed to reach the transition state.


Organic farming and landscape structure: effects on insect-pollinated plant diversity in intensively managed grasslands.
Parallel declines in insect-pollinated plants and their pollinators have been reported as a result of agricultural intensification. Intensive arable plant communities have previously been shown to contain higher proportions of self-pollinated plants compared to natural or semi-natural plant communities. Though intensive grasslands are widespread, it is not known whether they show similar patterns to arable systems nor whether local and/or landscape factors are influential. We investigated plant community composition in 10 pairs of organic and conventional dairy farms across Ireland in relation to the local and landscape context. Relationships between plant groups and local factors (farming system, position in field and soil parameters) and landscape factors (e.g. landscape complexity) were investigated. The percentage cover of unimproved grassland was used as an inverse predictor of landscape complexity, as it was negatively correlated with habitat-type diversity. Intensive grasslands (organic and conventional) contained more insect-pollinated forbs than non-insect pollinated forbs. Organic field centres contained more insect-pollinated forbs than conventional field centres. Insect-pollinated forb richness in field edges (but not field centres) increased with increasing landscape complexity (% unimproved grassland) within 1, 3, 4 and 5km radii around sites, whereas non-insect pollinated forb richness was unrelated to landscape complexity. Pollination systems within intensive grassland communities may be different from those in arable systems. Our results indicate that organic management increases plant richness in field centres, but that landscape complexity exerts strong influences in both organic and conventional field edges. Insect-pollinated forb richness, unlike that for non-insect pollinated forbs, showed positive relationships to landscape complexity reflecting what has been documented for bees and other pollinators. The insect-pollinated forbs, their pollinators and landscape context are clearly linked. This needs to be taken into account when managing and conserving insect-pollinated plant and pollinator communities.


Modification of Ti6Al4V Titanium Alloy Surface Layer in the Ozone Atmosphere.
The paper reports the results of a study on the Ti6Al4V titanium alloy involving the XPS (X-ray photoelectron spectroscopy) photoelectron spectroscopy method. The position of bands in the viewing spectrum serves as a basis for the qualitative identification of atoms forming the surface layer, while their intensity is used to calculate the aggregate concentration of these atoms in the analyzed layer. High-resolution spectra are used to determine the type of chemical bonds based on characteristic numerical values of the chemical shift. The paper also presents the 3D results of surface roughness measurements obtained from optical profiling, as well as the results of energy state measurements of the Ti6Al4V titanium alloy surface layer after ozone treatment. It was shown that the ozone treatment of the Ti6Al4V titanium alloy removes carbon and increases concentrations of Ti and V ions at higher oxidation states at the expense of metal atoms and lower valence ions. The modification of the surface layer in ozone atmosphere caused a 30% increase in the Ti element concentration in the surface layer compared to the samples prior to ozone treatment. The carbon removal rate from the Ti6Al4V titanium alloy samples amounted to 35%, and a 13% increase was noted in oxides. The tests proved that the value of the surface free energy of the Ti6Al4V titanium alloy increased as a result of ozone treatment. The highest increase in the surface free energy was observed for Variant 4 samples, and amounted to 17% compared to the untreated samples, while the lowest increase was equal to 14%. For the analyzed data, the maximum value of standard deviation was 0.99 [mJ/m2].


Policies that limit youth access and exposure to tobacco: a scientific neglect of the first stages of the policy process.
Policymakers can adopt and implement various supply-side policies to limit youth access and exposure to tobacco, such as increasing the minimum age of sale, limiting the number or type of tobacco outlets, or banning the display of tobacco products. Many studies have assessed the impact of these policies, while less is known about the preceding policy process. The aim of our review was to assess the available evidence on the preceding process of agenda setting, policy formulation, and policy legitimation. A systematic literature search was conducted using the PubMed and the Social Sciences Citation Index databases. After selection, 200 international peer-reviewed articles were identified and analyzed. Through a process of close reading, evidence based on scientific enquiry and anecdotal evidence on agenda setting, policy formulation and policy legitimation was abstracted from each article. Scientific evidence on the policy process is scarce for these policies, as most of the evidence found was anecdotal. Only one study provided evidence based on a scientific analysis of data on the agenda setting and legitimation phases of policy processes that led to the adoption of display bans in two Australian jurisdictions. The processes influencing the adoption of youth access and exposure policies have been grossly understudied. A better understanding of the policy process is essential to understand country variations in tobacco control policy.


Methodologies for detection of hemoglobin-based oxygen carriers.
Blood substitutes based on hemoglobin or hemoglobin-based oxygen carriers (HBOCs) are oxygen-carrying therapeutic agents developed for use in operations and emergencies in place of donated blood. Increased oxygen-carrying capacity through the use of blood substitutes could help elite athletes to lengthen endurance capacity and improve their performance. As blood substitutes become more readily available, it is essential that a qualitative detection method for their abuse in sport is available. Ideally, such a method would be simple and inexpensive. This study investigates methods that could be used as screening procedures to easily detect HBOCs in plasma and develops tests that can unequivocally confirm their presence. The investigation into the screening method indicates that the direct visual screening of plasma discoloration is the most appropriate with detection limits of less than 1% HBOC in plasma. Two methods are shown to confirm the presence of exogenous hemoglobin in plasma samples, size-exclusion chromatography with photodiode array detection and high-performance liquid chromatography analysis of enzymatic digests with detection by electrospray mass spectrometry. This work emphasizes the need for cooperation between drug developers and sports testing laboratories to ensure that methods for the detection of putative doping agents are available prior to product release.


Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis and potential targets for biologic treatment.
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are autoimmune diseases in which the small vessels are inflamed. Clinical observations suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data and animal models, particularly for myeloperoxidase-ANCA. An in vivo pathogenic role of ANCA directed to proteinase 3 has, however, not been fully substantiated. Additionally, the pathogenic role of B cells, T cells, and the alternative pathway of complement in AAV have been elucidated. Insight into these pathogenic pathways involved in AAV has opened and will further open new ways for targeted biologic treatment. In this review the pathogenesis of AAV and potential targets for biologic treatment are discussed.


Germline sequence analysis of RABL3 in a large series of pancreatic ductal adenocarcinoma patients reveals no evidence of deleterious variants.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of less than 10%. Individuals with a pathogenic germline variant in a pancreatic cancer susceptibility gene are at an increased risk of developing pancreatic cancer. Understanding the inherited genetic basis of pancreatic tumor development provides a unique opportunity to improve patient care and outcomes. For example, relatives of a patients with PDAC who have a pathogenic germline variant in a pancreatic cancer susceptibility gene are eligible for disease surveillance where cancers may be detected early, and 5-year survival greatly improved. Furthermore, for some patients with PDAC and a pathogenic germline variant in a pancreatic cancer susceptibility gene, their tumors may be susceptible to specific anti-cancer therapies. Recently, RABL3 was identified as a pancreatic cancer susceptibility gene. To validate these findings and inform clinical translation, we determined the prevalence of deleterious RABL3 variants in a large cohort of 1037 patients with PDAC that had undergone either whole genome or whole exome germline sequencing. We identified two synonymous variants and four missense variants classified as variants of unknown significance. We found no pathogenic RABL3 variants, indicating that the maximum prevalence of such variants in patients with PDAC is less than 0.36% (minor allele frequency 0, 97.5% one-sided confidence interval: 0-0.0036). This finding has important implications for germline genetic testing of patients with PDAC.


Bone morphogenetic proteins: facts, challenges, and future perspectives.
Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily, acting as potent regulators during embryogenesis and bone and cartilage formation and repair. Cell and molecular biology approaches have unveiled the great complexity of BMP action, later confirmed by transgenic animal studies. Genetic engineering allows for the production of large amounts of BMPs for clinical use, but they have systematically been associated with a delivery system, such as type I collagen and calcium phosphate ceramics, to ensure controlled release and to maximize their biological activity at the surgical site, avoiding systemic diffusion. Clinical orthopedic studies have shown the benefits of FDA-approved recombinant human BMPs (rhBMPs) 2 and 7, but side effects, such as swelling, seroma, and increased cancer risk, have been reported, probably due to high BMP dosage. Several studies have supported the use of BMPs in periodontal regeneration, sinus lift bone-grafting, and non-unions in oral surgery. However, the clinical use of BMPs is growing mainly in off-label applications, with robust evidence to ascertain rhBMPs' safety and efficacy through well-designed, randomized, and double-blind clinical trials. Here we review and discuss the critical data on BMP structure, mechanisms of action, and possible clinical applications.


Dissociation: cognitive capacity or dysfunction?
Dissociative experiences are mostly studied as a risk factor for dissociative pathology. Nonpathological dissociation is quite common in the general population, however, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through the experience of adverse life events. In a theoretical model, we propose that nonpathological dissociation is characterized by high levels of elaboration learning and reconstructive retrieval, for which enhanced levels of attentional and working memory abilities are a prerequisite. These characteristics, in general, seem to be representative for a higher ability to (re-)construct conscious experiences. We review some of our behavioral as well as neural (i.e., fMRI, ERPs) studies, suggesting that high dissociative individuals are characterized by heightened levels of attention, working memory and episodic memory. In nonpathological conditions a person may benefit from these dissociative abilities, although after adverse (e.g., traumatic) events the disposition may develop into dissociative pathology.


Longitudinal evaluation of innate immune responses to three doses of CoronaVac vaccine.
The adaptive immune responses induced by inactivated COVID-19 vaccine has been extensively studied. However, few studies have analyzed the impact of COVID-19 vaccination on innate immune cells. Here in this study, we recruited 62 healthcare workers who received three doses of CoronaVac vaccine and longitudinally profiled the alterations of peripheral monocytes and NK cells during vaccination. The results showed that both the monocyte and NK cell subsets distribution were altered, although the frequencies of the total monocyte and NK cells remained stable during the vaccination. Additionally, we found that both the 2nd and 3rd dose of CoronaVac vaccination elicited robust IFN-γ-producing NK cell response. Our data provided necessary insights on innate immune responses in the context of three homologous CoronaVac dose vaccination, and supplied immunological basis for the future design of inactivated vaccines against SARS-CoV-2 or other viruses.


Primary cutaneous tuberculosis of the pinna: an unusual presentation.
Cutaneous tuberculosis is an uncommon form of extra-pulmonary tuberculosis. A young female presented with chronic, non-healing ulceration involving the left pinna. Serology and skin biopsy suggested tuberculosis. Anti-tubercular therapy resulted in complete resolution of lesions. The recent increase in tuberculosis has led to myriad forms of the disease which often mimic non-specific dermatitis in morphology. The diagnostic dilemma encountered in such clinical settings has prompted us to present this unusual case. On review of literature, we could find only three case reports of ulcerative form of primary tuberculosis of pinna.


Antimicrobial studies of hydrazone complexes of Hg(II) and Fe(II) divalent metal ions.
The antibacterial, antifungal and antitubercular activities of Hg(II) and Fe(II) complexes of hydrazone were studied. All the complexes have been screened against Staphylococcus aureus, Salmonella typhi, Candida albicans, Aspergillus niger, Saccharomyces cerevisiae and Mycobacterium tuberculosis H37Rv and found to be more toxic than the parent ligand. The activity increased in the order [5-methyl-3-oximino-hexan-2-one-hydrazone]2 Fe(II) < [5-methyl-3-oximino-hexan-2-one-hydrazone]2 Hg(II) < 3-oximino-hexan-2-one-phenylhydrazone]2 Fe(II) < [5-methyl-3-oximino-hexan-2-one-phenylhydrazone]2 Hg(II) for antibacterial and antifungal activity.


Molecular simulation of a model of dissolved organic matter.
A series of atomistic simulations was performed to assess the ability of the Schulten dissolved organic matter (DOM) molecule, a well-established model humic molecule, to reproduce the physical and chemical behavior of natural humic substances. The unhydrated DOM molecule had a bulk density value appropriate to humic matter, but its Hildebrand solubility parameter was lower than the range of current experimental estimates. Under hydrated conditions, the DOM molecule went through conformational adjustments that resulted in disruption of intramolecular hydrogen bonds (H-bonds), although few water molecules penetrated the organic interior. The radius of gyration of the hydrated DOM molecule was similar to those measured for aquatic humic substances. To simulate humic materials under aqueous conditions with varying pH levels, carboxyl groups were deprotonated, and hydrated Na+ or Ca2+ were added to balance the resulting negative charge. Because of intrusion of the cation hydrates, the model metal-humic structures were more porous, had greater solvent-accessible surface areas, and formed more H-bonds with water than the protonated, hydrated DOM molecule. Relative to Na+, Ca2+ was both more strongly bound to carboxylate groups and more fully hydrated. This difference was attributed to the higher charge of the divalent cation. The Ca-DOM hydrate, however, featured fewer H-bonds than the Na-DOM hydrate, perhaps because of the reduced orientational freedom of organic moieties and water molecules imposed by Ca2+. The present work is, to our knowledge, the first rigorous computational exploration regarding the behavior of a model humic molecule under a range of physical conditions typical of soil and water systems.


A Female-Biased Odorant Receptor from Apolygus lucorum (Meyer-Dür) Tuned to Some Plant Odors.
Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) is a serious pest of cotton, jujube, grape and many other crops around the world. Understanding how olfactory information directs this insect to its host plants may provide environment-friendly approaches to the control of its population in agriculture. In our study, we cloned an odorant receptor gene, AlucOR46, that was specifically expressed in antennae and female-biased. Functional expression of AlucOR46 in Xenopus oocytes showed that it is tuned to six plant volatiles (S)-(-)-Limonene, (R)-(+)-Limonene, (E)-2-Hexenal, (E)-3-Hexenol, 1-Heptanol and (1R)-(-)-Myrtenol. Electroantennogram (EAG) recordings revealed that all six compounds could elicit electrophysiological responses from the antennae of A. lucorum, higher in females. Our results are in agreement with previous reports showing that (E)-2-Hexenal could attract female A. lucorum in behavior experiments. These results suggest that AlucOR46 might play an important role in locating the host plants of A. lucorum and therefore represents a suitable target for green pest control.


A comparison of the osmotic pressures along the digestive tract of the domestic fowl and the rabbit.
1. The osmotic pressures of the contents of the alimentary tract from the adult hen and cockerel and rabbit were measured. 2. In the rabbit osmolality of the fluids from the different segments of the digestive tract was similar (331 &/- 12 mOm) and slightly hypertonic to blood plasma (297 &/- 3-12 mOsm). 3. In the hen osmotic pressures were: crop 537, gizzard 312, duodenum 571, proximal jejunum 650, distal jejunum 573, proximal ileum 514 and distal ileum 451 mOsm. Only osmolality of the crop contents was influenced by egg formation. 4. In the cockerel osmotic pressure in the alimentary tract followed the same pattern as the hen and was modified by the time of day. 5. Plasma osmolality in the fowl was about 320 mOsm. Absorption of water across the proximal jejunum is achieved therefore against a gradient of about 330 mOsm in the female and 420 mOsm in the male fowl.


Treatment with Granulocyte-colony Stimulating Factor (G-CSF) is not associated with Increased Risk of Brain Metastasis in Patients with De Novo Stage IV Breast Cancer.
Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.


[Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring].
To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring. A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored. The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027). Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.