Study of the molecular structure, ionization spectrum, and electronic wave function of 1,3-butadiene using electron momentum spectroscopy and benchmark Dyson orbital theories.
The scope of the present work is to reconcile electron momentum spectroscopy with elementary thermodynamics, and refute conclusions drawn by Saha et al. in J. Chem. Phys. 123, 124315 (2005) regarding fingerprints of the gauche conformational isomer of 1,3-butadiene in electron momentum distributions that were experimentally inferred from gas phase (e,2e) measurements on this compound [M. J. Brunger et al., J. Chem. Phys. 108, 1859 (1998)]. Our analysis is based on thorough calculations of one-electron and shake-up ionization spectra employing one-particle Green's function theory along with the benchmark third-order algebraic diagrammatic construction [ADC(3)] scheme. Accurate spherically averaged electron momentum distributions are correspondingly computed from the related Dyson orbitals. The ionization spectra and Dyson orbital momentum distributions that were computed for the trans-conformer of 1,3-butadiene alone are amply sufficient to quantitatively unravel the shape of all available experimental (e,2e) electron momentum distributions. A comparison of theoretical ADC(3) spectra for the s-trans and gauche energy minima with inner- and outer-valence high-resolution photoelectron measurements employing a synchrotron radiation beam [D. M. P. Holland et al., J. Phys. B 29, 3091 (1996)] demonstrates that the gauche structure is incompatible with ionization experiments in high-vacuum conditions and at standard temperatures. On the other hand, outer-valence Green's function calculations on the s-trans energy minimum form and approaching basis set completeness provide highly quantitative insights, within approximately 0.2 eV accuracy, into the available experimental one-electron ionization energies. At last, analysis of the angular dependence of relative (e,2e) ionization intensities nicely confirms the presence of one rather intense pi(-2) pi(*+1) satellite at approximately 13.1 eV in the ionization spectrum of the s-trans conformer.


The truth and consequences of enzymatic detergents.
Enzymatic detergents are widely used to clean gastrointestinal endoscopes before high-level disinfection. Although proper use of enzymatic detergents may appear straightforward, common misuses include failure to dilute the enzymatic detergent, overdilution of enzymatic detergent, use of expired enzymatic detergent, inadequate exposure time, and failure to rinse the enzymatic detergent from the instrument being cleaned. Each type of misuse has its own rationale. In these studies, the authors show by high-performance liquid chromatography that the type of enzymatic detergent and the dilution and rinsing of enzymatic detergents affect the amount of residual high-level disinfectant (ortho-phthalaldehyde) left on test segments of flexible endoscope insertion tubes. The authors also qualitatively demonstrate that proteinaceous material, which is stained a dark color by ortho-phthalaldehyde (OPA), remains on colonoscopes that have been cleaned with improperly diluted or rinsed enzymatic detergents. These findings emphasize the importance of diluting and using enzymatic detergents exactly as directed by their manufacturers to reduce bioburden and residual amounts of high-level disinfectant on flexible endoscopes.


Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity.
The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells. The GWH1-based nanoparticles combine clinically appealing properties of nanoscale materials with full biocompatibility, structural and functional plasticity and biological efficacy exhibited by proteins. Because of the largely implemented biological fabrication of recombinant protein drugs, the protein-based platform presented here represents a novel and scalable strategy in antimicrobial drug design, that by solving some of the limitations of AMPs offers a promising alternative to conventional antibiotics. The low molecular weight antimicrobial peptide GWH1 has been engineered to oligomerize as self-assembling protein-only nanoparticles of around 50nm. In this form, the peptide exhibits potent and broad antibacterial activities against both Gram-positive and Gram-negative bacteria, without any harmful effect over mammalian cells. As a solid proof-of-concept, this finding strongly supports the design and biofabrication of nanoscale antimicrobial materials with in-built functionalities. The protein-based homogeneous composition offer advantages over alternative materials explored as antimicrobial agents, regarding biocompatibility, biodegradability and environmental suitability. Beyond the described prototype, this transversal engineering concept has wide applicability in the design of novel nanomedicines for advanced treatments of bacterial infections.


Autoimmune sensorineural hearing loss: the otology-rheumatology interface.
Autoimmune sensorineural hearing loss (SNHL) is a rare clinical entity characterized by a progressive fluctuating bilateral asymmetric SNHL that develops over several weeks to months. Vestibular symptoms, tinnitus and aural fullness are present in up to 50% of patients. Due to the lack of specific diagnostic tests, both clinical suspicion and responsiveness to corticosteroids are the pillars for the diagnosis of autoimmune SNHL. The evaluation of patients in whom this condition is suspected should include a detailed history and physical examination, an audiogram, an MRI and a limited laboratory workup to exclude secondary causes of hearing loss. The low frequency of this condition, the heterogeneity in the designs of the available studies and the absence of randomized trials comparing treatment responses and assessing long-term outcomes are some of the factors accounting for the limited evidence to guide the clinician in the approach to the diagnosis and treatment of autoimmune SNHL.


[Changes of complement in recurrent abortion and pregnancy loss with antiphospholipid antibody positive].
In order to know the comlement activation, the changes of compliment were evaluated in recurrent abortion and pregnancy loss patients with antiphospholipid antibody (APA) positive. Serum samples were taken from 82 patients with more than 2 recurrent abortion patients and/or pregnancy loss. Fifty eight cases of 82 patients were APA and antinuclear antibody negative without autoimmune disease. Anticardiolipin antibody (ACA), anti CL/beta2-GPI antibody (CL/beta2-GPI) were measured using ELISA. Lupus anticoagulant (LAC) was measured using diluted RVVT. CH50 and C3 and C4 were measured as complements. The number of positive cases of ACA, CL/beta2-GPI, LAC was 23, 9 and 5 cases, respectively. The levels (mean+/-SD) of CH50, C3 and C4 in ACA positive and negative cases were 38.8+/-8.3 U/ml, 82.7+/-20.1 mg/dl, 18.5+/-5.7 mg/dl and 42.4+/-6.9 U/ml, 93.5+/-17.6 mg/dl, 21.1+/-4.6 mg/dl, respectively. The levels of CH50, C3 and C4 in positive cases were significantly lower than negatives. The levels of CH50, C3 and C4 in CL/beta2-GPI and LAC positive cases were also significantly lower than negatives. The comlement activation was demonstrated in recurrent abortion and pregnancy loss with antiphospholipid antibody positive.


Spontaneous regression of a malignant primary bone tumour.
A histologically confirmed malignant, primary bone tumour in the pelvis, presumably an osteosarcoma, underwent spontaneous regression. The large tumour was inoperable and gave rise to severe pain as well as difficulty in walking. After 2 years of progression, with increasing desition improved spontaneously, and at present the patient is alive, almost symptom-free, after 6 years follow-up.


Emerging Trends in the Pathological Research of Human Papillomavirus-positive Oropharyngeal Squamous Cell Carcinoma.
Oropharyngeal squamous cell carcinomas (OPSCCs) have shown an alarming rate of increase in incidence over the past several decades, markedly in men. In the United States, transcriptionally-active human papillomavirus (HPV), particularly HPV 16, has become the highest contributive agent of OPSCCs, affecting approximately 16,000 people a year. Compared to patients with HPV-negative OPSCCs, patients with HPV-positive OPSCCs exhibit better health responses to chemoradiotherapy and an overall increase in long-term survival. Despite promising treatment options, many OPSCCs are discovered at an advanced stage, and ~20% of cases will recur after definitive treatment. Therefore, extensive research is ongoing to identify new targets for precision treatment and to stratify tumor prognosis. The aim of this review is to capture the most updated research on HPV-positive OPSCCs, emphasizing their relevance as potential new targets for precision medicine and survival prognosis.


Birth asphyxia survivors in a developing country.
Determine the baseline incidence of birth asphyxia in neonatal intensive care unit (NICU) survivors in a developing country and the early neurodevelopmental outcomes of such infants. This cross-sectional, prospective study collected diagnostic and examination findings on all infants seen in the University of Zambia NICU follow-up clinic over a 4-week period. Of the 182 infants, 42 (23%) had a clinical diagnosis of birth asphyxia. Of 42 infants with birth asphyxia, 13 (31%) had an abnormal neurologic examination during the clinic visit; in contrast, 13 of 141 infants without birth asphyxia (9%) had an abnormal examination (odds ratio 4.4, 95% confidence interval: 1.8, 10.4). Birth asphyxia survivors account for almost a quarter of NICU survivors in a developing country and half of those with an abnormal neurologic examination. Studies are necessary to determine the percent of birth asphyxia survivors who have permanent motor and cognitive disabilities.


Detection of pim-1 mRNA in prostate cancer diagnosis.
Pim-1 plays an important role in the apoptosis, proliferation, differentiation of cancer cells and progression of cancer. In this study we detected the expression of pim-1 mRNA in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and explored its diagnostic value for PCa. The prostate tissues were collected from 23 patients with PCa, 37 patients with BPH, and 3 healthy volunteers. Pim-1 mRNA expression levels in these samples were determined by the quantitative real-time PCR (QRT-PCR). The differences of expression were calculated based on a standard curve. The ratio of pim-1 mRNA to beta-actin in the normal prostate, BPH, and PCa were 1.05 +/- 0.04, 2.57 +/- 0.74 and 4.45 +/-0.63, respectively. The differences among PCa, BPH and NT were significant (P < 0.05, respectively). Detecting pim-1 mRNA expression by QRT-PCR provides a reliable metric for the diagnosis of PCa.


Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry.
Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context. 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation-perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation. Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA). The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.


A better deal for neonatal care at last.
All those concerned with the care of premature and sick newborn babies have been calling for a review of neonatal services for almost a decade. Now, at last, the long-awaited Department of Health (DoH) review of neonatal intensive care services in England has been published.


Diverting Hydrogenations with Wilkinson's Catalyst towards Highly Reactive Rhodium(I) Species.
The addition of Barton's base has a dramatic effect on the classic rhodium(III)-mediated hydrogenations promoted by Wilkinson's catalyst. Following the initial oxidative addition, a barrierless reductive elimination of HCl from the traditional rhodium(III) intermediates instantly produces a rhodium(I) monohydride species, which is remarkably reactive in the hydrogenation of several internal alkynes and functionalized trisubstituted alkenes. The direct formation of this species is unprecedented upon addition of molecular hydrogen and its catalytic potential has been hitherto barely explored.


E-cadherin deficiency promotes prostate macrophage inflammation and bladder overactivity in aged male mice.
Decreased E-cadherin immunostaining is frequently observed in benign prostatic hyperplasia (BPH) and was recently correlated with increased inflammation in aging prostate. Homozygous E-cadherin deletion in the murine prostate results in prostate inflammation and bladder overactivity at 6 months of age. However, this model is limited in that while E-cadherin is significantly reduced in BPH, it is not completely lost; BPH is also strongly associated with advanced age and is infrequent in young men. Here, we examined the functional consequences of aging in male mice with prostate luminal epithelial cell-specific E-cadherin heterozygosity. In control mice, aging alone resulted in an increase in prostate inflammation and changes in bladder voiding function indicative of bladder underactivity. At 24 months of age, mice with prostate-specific Cre-mediated heterozygous deletion of E-cadherin induced at 7 weeks of age developed additional prostatic defects, particularly increased macrophage inflammation and stromal proliferation, and bladder overactivity compared to age-matched control mice, which are similar to BPH/LUTS in that the phenotype is slow-progressing and age-dependent. These findings suggest that decreased E-cadherin may promote macrophage inflammation and fibrosis in the prostate and subsequent bladder overactivity in aging men, promoting the development and progression of BPH/LUTS.


The taxonomy of multivalent orientation: six modes of alternate or one?
Unlike adjacent I and II, alternate I and II orientations of interchange and tetrasome quadrivalents can be considered extremes within one particular population of orientations (alternate) and thus lack sufficient distinction to justify a separate taxonomic status. Within the population up to six types may be distinguished, but the biological significance of this distinction is small.


Forced degradation studies: current trends and future perspectives for protein-based therapeutics.
Forced degradation (FD) studies (stress testing) are an integral part of pharmaceutical product development. The design and execution of these studies require thorough planning and coordination through the various stages of development as well as post-approval commercial operations. This is particularly crucial in the case for protein-based therapeutics due to complexity of the molecular structure as well as the potential influence of the manufacturing process on product attributes. Often, FD study applications are linked to specific product development in a phase-specific and case-by-case manner with differing purposes and focus. Expert commentary: This paper summarizes some key FD approaches commonly employed in the industry and provides considerations on study design strategies and database management through the course of the product lifecycle.


The relationship of depth of penetration and tumor size to the number of positive nodes in Dukes C colorectal cancer.
This study examines the interrelationships of depth of penetration, tumor size, and the number of positive nodes in Dukes C colorectal cancer. The results indicated that depth of tumor penetration was related to both tumor size and the number of positive regional lymph nodes. Tumors with positive nodes which failed to penetrate the muscularis propria (C1) were smaller, and were associated with fewer positive nodes than were tumors penetrating all coats of the bowel (C2). Although tumor penetration was related to tumor size and the number of positive nodes, no correlation was evident between tumor size and the number of positive nodes within the C1 and C2 patient subsets. The data underscore the biological significance of depth of tumor penetration and militate against tumor size as a prognostic discriminant in patients with colorectal cancer. The findings represent a contradiction to the prevailing biological concepts relative to the behavior of solid tumors as reflected in the TNM classification scheme.


Histological Study of Discoid Lateral Meniscus in Children and Adolescents: Morphogenetic Considerations.
Background Discoid lateral meniscus is the most frequent variant of the meniscus. Few studies have focused on the histology of discoid menisci. The aim of the present study was to report the histological findings of discoid lateral meniscus in children and adolescents, after arthroscopic partial resection, to give a possible explanation of its developmental etiology. Methods Five patients aged 9, 10, 13, 15, and 17 years were operated on for a 1-piece excision of a discoid lateral meniscus, and the specimens were histologically examined. Results The extracellular matrix showed a different distribution and characteristics depending on the different side of the meniscus. Irregularly oriented collagen fibers in discoid lateral meniscus were found. Cells of different shapes were observed depending on the surficial or deep location in the tissue. There were no blood vessels in the inner part of discoid lateral meniscus. Conclusion The findings of the current study seem to confirm that discoid lateral meniscus arises from variant morphogenesis. Furthermore, the altered distribution and shape of the cells and disorganization of collagen fibers (irrespectively of the age of the patients) may predispose discoid lateral meniscus to degeneration, damage, and tear in young patients also. Level of Evidence Level of evidence 4 (case series).


HEAT ADAPTATION AND ION EXCHANGE IN BACILLUS MEGATERIUM SPORES.
A new spore phenomenon is described in which induction of increased heat resistance occurs during the process of heating. In buffered environments the acid form of dormant mature bacterial spores shows a temperature dependent adaptation to heat which is correlated with the rate of uptake of Ca(OH)(2) by titration at constant p(H) in neutral salt solution.


Multimodality tumor control and living donor transplantation for unresectable hepatocellular carcinoma.
Liver transplantation (LT) is an acceptable mode of treatment for selected patients with unresectable hepatocellular carcinoma (HCC). However, due to the scarcity of cadaveric donor organs, it is considered desirable for patients to opt for living donor liver transplantation (LDLT) or, for those not being transplanted soon, to have some form of tumor control therapy. Such an approach in our program is analyzed and reported. At our institution, 42 LTs were performed between October 1999 and April 2003. Of these, 18 recipients (15 men, 3 women) had 27 HCC. The average number and size of HCC was 1.59 (1 to 4) and 2.31 (0.2 to 6.5) cm, respectively. Thirteen (72%) patients were transplanted primarily for the HCC, whereas five (28%) others were incidental HCC cases. Seven patients (5 LRLT, 2 cadaveric LT) were transplanted soon after listing, and thus did not require tumor control therapy. Six patients waited for 11 (6 to 19) months before LT. Three patients underwent microwave coagulation therapy, and one had additional alcohol injections. One patient received the novel PIAF (cisplatin, interferon, adriamycin, and 5-FU) chemotherapy regimen followed by selective internal irradiation (SIR) treatment. One patient received conformal radiation therapy and another received SIR treatment before LT. Besides 2 postoperative deaths, the remaining 16 patients have been well, with a mean follow-up of 20.4 (3.6 to 41.2) months. In conclusion, for patients with unresectable HCC, in areas with poor cadaveric donor rate, living donation should be the first option. If a suitable live donor is not available, aggressive multimodality therapy is recommended while waiting for cadaveric LT.


Acetylation of human serum albumin by acetylsalicylic acid.
Human serum albumin is acetylated when exposed to acetylsalicylic acid (aspirin) under physiologic conditions in vitro. Indications are that a similar phenomenon occurs in vivo after ingestion of aspirin.


[Laboratory diagnosis of pertussis. Role of serology].
Culture is the reference method for the diagnosis of infection by Bordetella pertussis. Nevertheless, delayed sample collection and previous antibiotic treatment can limit culture sensitivity. In principle, direct immunofluorescence provides immediate diagnosis. It is, however, a subjective procedure that shows low sensitivity and specificity. PCR techniques increase culture sensitivity while maintaining high specificity, but their performance decreases along the evolution of the disease. Serologic methods are the main alternative for cases in which diagnosis is delayed. Current recommendations center on ELISA techniques that include purified antigens, such as filamentous hemaglutinin, and particularly, pertussis toxin. Traditionally, serological diagnosis requires confirmation by demonstrated seroconversion, but now the possibility of diagnosis based on titration of a single serum sample is being evaluated.


Genus-optimized strategy for the identification of chlamydial type III secretion substrates.
Among chlamydial virulence factors are the type III secretion (T3S) system and its effectors. T3S effectors target host proteins to benefit the infecting chlamydiae. The assortment of effectors, each with a unique function, varies between species. This variation likely contributes to differences in host specificity and disease severity. A dozen effectors of Chlamydia trachomatis have been identified; however, estimates suggest that more exist. A T3S prediction algorithm, SVM-based Identification and Evaluation of Virulence Effectors (SIEVE), along with a Yersinia surrogate secretion system helped to identify a new T3S substrate, CT082, which rather than functioning as an effector associates with the chlamydial envelope after secretion. SIEVE was modified to improve/expand effector predictions to include all sequenced genomes. Additional adjustments were made to the existing surrogate system whereby the N terminus of putative effectors was fused to a known effector lacking its own N terminus and was tested for secretion. Expansion of effector predictions by cSIEVE and modification of the surrogate system have also assisted in identifying a new T3S substrate from C. psittaci. The expanded predictions along with modifications to improve the surrogate secretion system have enhanced our ability to identify novel species-specific effectors, which upon characterization should provide insight into the unique pathogenic properties of each species.


Tacrolimus-Induced Akinetic Mutism or Epidural Catheter Migration: A Case Report.
Differential diagnosis of the underlying cause of new-onset total body paralysis can be challenging and unsatisfying. In akinetic mutism, a rare side effect of tacrolimus, patients become apathetic, mute, and lose voluntary muscle movement. Epidural subarachnoid migration can present with similar symptoms. Delayed emergence/paralysis after anesthesia can include the common culprits of residual operative medications, stroke, as well as tacrolimus-induced akinetic mutism and thoracic epidural migration. We present a case of new-onset total body paralysis, presenting on postoperative day 1 following a double-lung transplant in a patient started on tacrolimus with a thoracic epidural catheter in place.


Site-specific antibodies as probes of the topology and function of the human erythrocyte glucose transporter.
Antibodies were raised against synthetic peptides corresponding to most of the regions of the human erythrocyte glucose transporter predicted to be extramembranous in the model of Mueckler, Caruso, Baldwin, Panico, Blench, Morris, Lienhard, Allard & Lodish [(1985) Science 229, 941-945]. Most of the antibodies (17 out of a total of 19) recognized the intact denatured protein on Western blots. However, only seven of the antibodies recognized the native membrane-bound protein, even after its deglycosylation. These antibodies, against peptides encompassing residues 217-272 and 450-492 in the hydrophilic central and C-terminal regions of the transporter, bound to the cytoplasmic surface of the erythrocyte membrane. This finding is in agreement with the prediction of the model that these regions of the sequence are cytoplasmic. Antibodies against peptides from the central cytoplasmic loop of the transporter were found to inhibit the binding of cytochalasin B to the membrane-bound protein, whereas antibodies against the C-terminal region had no effect. The anti-peptide antibodies were then used to map the sequence locations of fragments of the transporter arising from tryptic digestion of the membrane-bound protein. This in turn enabled the epitopes for a number of anti-transporter monoclonal antibodies to be located within either the central cytoplasmic loop or the C-terminal region of the protein. Of those monoclonal antibodies which inhibited cytochalasin B binding to the protein, all but one were found to have epitopes within the central region of the sequence. In conjunction with the results of the anti-peptide antibody studies, these findings indicate the importance of this part of the protein for transporter function.


A Mechanistic Review of Methotrexate and Celecoxib as a Potential Metronomic Chemotherapy for Oral Squamous Cell Carcinoma.
The combination of low-dose methotrexate and celecoxib as metronomic chemotherapy (MCT) is a novel therapy, believed to act by modulating the immune response, inhibiting angiogenesis and its cytotoxic action, though the exact mechanism of action is unclear. Clinically, MCT was found to be very effective in delaying tumor progression in patients with head and neck squamous cell carcinoma in both curative and palliative settings. This review was aimed to give a brief insight into the mechanism of action and potential molecular alterations of MCT in the treatment of oral cancers taking into consideration the various in vivo and in vitro studies.


Pharmacotherapy for Perinatal Depression.
Perinatal depression is associated with serious risks for the mother, baby, and family. When considering treating perinatal depression with a drug indicated for the treatment of depression, the major concerns are whether the drug increases the risks of teratogenicity, pregnancy complications, poor neonatal adaptation, or neurodevelopmental disorders. Although different studies have produced different results, the majority have not shown increases in risk for selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, or the noradrenergic/dopaminergic drug bupropion. In this review we will discuss the reproductive safety data for these medications as well as monoamine oxidase inhibitors and benzodiazepines.


"So mean and cranky, I could bite my mother": an ethnosemantic analysis of women's descriptions of premenstrual change.
Textual analysis was used to examine responses to an open ended question about women's experiences of premenstrual change. The question was the final item of the Premenstrual Assessment Form (PAF), a retrospective PMS questionnaire. Of the 336 women who answered the PAF, 261 provided a written narrative summary. We found a logical hierarchy of distinctions covering the presence or absence of changes, their timing, and attributive aspects, and a final cumulative distinction in which women provided information about the consequences of their premenstrual change. Although attribute aspects mirrored the PAF, distinctions in timing and in the cumulative effect of changes differed. The analysis suggests that questionnaires could be designed which more precisely reflect premenstrual change.


Hepatocyte culture on biodegradable polymeric substrates.
The interactions of primary rat liver cells with biodegradable polymeric substrates were investigated in vitro to assess the suitability of the polymer materials for use in cell transplantation devices. The kinetics of cell adhesion to, and the growth and biochemical function of cells maintained on, films formed from poly (D,L-lactic-co-glycolic acid, 88: 12) (PLGA) or from a 50/50 (w/w) blend of PLGA and poly (L-lactic acid) (PLLA) were evaluated in comparison to two control substrates, matrigel coated or collagen-coated polystyrene petri dishes. The rate of cell adhesion to both types of polymeric substrates was similar to the rate of adhesion to the collagen control substrate, but of the two polymers, only the blend was suitable for extended culture. Hepatocytes maintained on the polymer blend films showed retention of differentiated cell function as measured by the rate of albumin secretion-the rate of albumin secretion by cells on the films was the same as the rate for cells on matrigel and reached a level in the range of reported in vivo levels (140-160 microg/10(6) cells/24 h). In contrast, albumin secretion by hepatocytes maintained on collagen-coated polystyrene culture dishes declined over five days to a level one third that of the initial level and one fifth that of cells maintained on the polymer blend films on day five. Such retention of differentiated cell function by hepatocytes in culture has previously been observed only when hepatocytes were cultured in the presence of exogenous extracellular matrix proteins or were cocultured with another cell type. In addition to retention of differentiated function, the cells maintained on the polymer blend films also displayed rates of DNA synthesis similar to controls maintained on collagen-coated polystyrene, a substrate optimal for DNA synthesis.


Coexisting Membranous Nephropathy and IgA Nephropathy.
We herein present a case of a 14-year-old boy with the histological features of coexisting membranous nephropathy (MN) and IgA nephropathy (IgAN). Asymptomatic hematuria/proteinuria was initially detected in school urinary screening, with treatments including oral corticosteroids leading to complete remission. Cases of coexisting MN and IgAN are very rare among the pediatric population; however, the overlap of these two nephropathies does not always imply a deleterious clinical outcome in pediatric cases.


Food intakes of children, the DHSS, and the prevention of heart disease.
The DHSS recently reported on school children's food intakes (1). Although the type of fat eaten is clearly an important issue, the DHSS study did not analyse the fat intake for its saturated and essential fatty acid content. We have explored the intakes of the children for fibre, sugar and saturated fats as well as additional vitamins and trace elements, not reported by the DHSS. The data from the DHSS survey was presented as a summary of the main food types eaten. They aggregated some food groups e.g. meat and meat products, fish and fish products, cakes and biscuits. While this approach might make little difference to protein intakes, it may be expected to make a difference to fat and essential fatty acid intakes. We have re-analyzed the childrens food intakes keeping within the confines of the food groups reported. We had to rely on certain assumptions about the nature of an 'average' diet; we therefore explored the possibility that our assumption of an average diet was incorrect and examined a worse and a better situation to define how much the nutrient intake varied. The result of the analyses illustrate an important principle in the context of the present concern for food and health. The only way in which we could satisfy NACNE and COMA recommendations for fat, saturated fat, fibre and sugar, without a radical change in eating habits, was by simply replacing half the 'junk' foods by an isocaloric amount of fresh fruit and vegetables. In addition there was a marked improvement in the intakes fo beta-carotene, vitamin C, B6 and folic acid. These improvements in diet are of particular importance to children as it is well known that the period most vulnerable to nutritional distortions is during growth and development. No matter which way we looked at the data is clear that not only are the school children's diets unsatisfactory from the view point of prevention of cardiovascular disease in later life but they also leave much to be desired from the view point of the wide range of nutrients known to be important for general health, growth and development. If this is true for the mean values obtained, it will be even more true for the 'high risk groups'.


The changing trends and profile of pneumocystosis mortality in the United States, 1999-2014.
Pneumocystosis (PCP) mortality in the U.S. has received less attention in recent years. This study describes recent trends in mortality and the estimated burden of PCP in the U.S., using the national multiple cause of death data during 1999-2014. PCP mortality rates were calculated for age, sex, race and year. Demographic differences were presented for decedents with and without a human immunodeficiency virus (HIV) co-diagnosis. Matched odds ratios (MOR) were generated to describe associations between non-HIV conditions and PCP mortality. In total, 11 512 PCP deaths occurred during 1999-2014. Annual age-adjusted PCP mortality decreased over this time period, from 0.479 to 0.154 per 100 000 population (1999 vs 2014 respectively). Over two-thirds of decedents were male and Blacks had the highest mortality as compared to Whites. HIV co-diagnosis accounted for 48% of all PCP deaths in 2014 vs 71% in 1999. Comorbid conditions such as connective tissue disorders (MOR=12.29; 95% confidence interval=[10.26, 14.71]) were associated with a PCP diagnosis. Productivity losses amounted to >$12 billion during the study period. Although widespread use of antiretroviral therapy and PCP prophylaxis for HIV infection likely contributed to the overall decline in PCP deaths during 1999-2014, a continual need exists to prevent and treat this fungal disease in immune-compromised populations that are not infected with HIV.


[Problems in the diagnosis and surgical care of thoracoabdominal wounds].
The article presents an 11 years experience in work of a specialized department of thoracoabdominal trauma with an analysis of treatment of 292 wounded. The main causes of the thoracoabdominal wounds (TAW) were knife stabs (96.2% of the patients). The diagnosis of injuries to vital organs of the chest and abdomen is known to be very difficult. The X-ray analysis is one of major diagnostic methods for TAW. Emergency thoracoscopy is of great significance in diagnosis of intrathoracic injuries and laparocentesis and laparoscopy are of great value for intraperitoneal wounds. The sequence of measures and surgery volume must be determined by the wound type and the severity of injuries of the internal organs which gives better results of treatment of such patients. Postoperative complications were noted in 9.1% of the wounded. Lethality was 5.1%.


Intracranial ependymomas and ependymoblastomas.
Nineteen cases of intracranial ependymal tumors were reviewed to examine the prognostic factors influencing survival of the patients with this disease. The two most important predictive factors in relation to survival status were a histologic grade of tumors and a presence of hydrocephalus. The clinicopathological correlation in this study has supported the view of two distinct ependymal tumors; more curable ependymomas and highly malignant ependymoblastomas .


[Nephropathy in Patients Undergoing Cancer Drug Therapy - Platinum Derivatives(Cisplatin and Carboplatin)].
Cisplatin, a first-generation platinum derivative, is one of the most widely used anticancer agents and can treat a broad spectrum of malignancies. Cisplatin-induced nephrotoxicity is a major dose-limiting side effect resulting from damage to the proximal tubules of the kidney. This nephrotoxicity can be prevented by lowering the concentration of cisplatin and shortening the period of cisplatin exposure to the proximal tubules. In clinical practice, high-volume hydration(>3 L intravenous isotonic saline), forced diuresis(mannitol and/or furosemide), and magnesium supplementation have been generally used to lower the risk of cisplatin-induced nephrotoxicity. Short hydration(short-term, low-volume hydration with oral fluid intake)has recently been undertaken among patients with reserved renal function and good performance status, especially in outpatient settings. Carboplatin is a second-generation platinum-based agent that is almost completely excreted from the kidneys following its administration. Its pharmacokinetics can be predicted based on the glomerular filtration rate(GFR). The area under the blood concentration-time curve(AUC), an indicator of drug exposure volume in the body, is closely correlated with hematotoxicity and antitumor effect. It is now a widespread practice to set carboplatin doses based on the GFR after establishing a target AUC. This article describes the characteristics of these 2 platinum-based drugs, focusing on the recommendations based on the recently published guidelines regarding nephropathy in patients undergoing cancer drug therapy.


Retinal Vein Occlusions.
Retinal vein occlusions (RVOs) have been defined as retinal vascular disorders characterized by dilatation of retinal veins with retinal and subretinal hemorrhages, macular edema, and a varying degree of retinal ischemia. Retinal angiography, either as fluorescein and indocyanine green (ICG) angiography or in the form of optical coherence tomography (OCT)-based angiography, is essential for the diagnosis and assessment of the prognosis of RVOs. It allows the differentiation of diverse types of RVOs, such as perfused or nonperfused, as well as the detection of different modalities in the natural history of RVOs. OCT angiographic imaging in combination with dye angiography (fluorescein or ICG) is the most effective method to assess the amount and location of cystoid macular edema and the persistence, regression, and degree of ischemia. OCT can additionally display the presence and integrity of the outer limiting membrane and of the inner and outer segments of the photoreceptors as useful biomarkers for the prognosis and as a guide for the treatment of RVO. Due to the relatively often benign and self-limiting course of nonischemic RVOs, therapy may initially be delayed. If macular edema extends into the foveolar region and persists, intravitreal medical therapy including steroids (triamcinolone; fluocinolone or dexamethasone in slow-release devices) and/or anti-VEGF (vascular endothelial growth factor) drugs (bevacizumab, ranibizumab, aflibercept) may be intravitreally administered, avoiding the irreversibly destructive effect of laser coagulation, which previously was applied in a 'grid' pattern over the extrafoveolar leaking area. The side effects of intraocularly applied steroids in relatively young patients including cataract formation and ocular hypertension have to be considered.


Short-memory traders and their impact on group learning in financial markets.
This article highlights several issues from simulating agent-based financial markets. These all center around the issue of learning in a multiagent setting, and specifically the question of whether the trading behavior of short-memory agents could interfere with the learning process of the market as whole. It is shown in a simple example that short-memory traders persist in generating excess volatility and other features common to actual markets. Problems related to short-memory trader behavior can be eliminated by using several different methods. These are discussed along with their relevance to agent-based models in general.


Prevalence of Salmonella enterica in bulk tank milk from US dairies as determined by polymerase chain reaction.
Samples of bulk tank milk from dairies across the United States, taken as part of the National Animal Health Monitoring System Dairy 2002 survey, were analyzed for the presence of Salmonella enterica using a commercially available real-time polymerase chain reaction (PCR) kit. Samples from 854 farms in 21 states were collected and enriched in tetrathionate broth to amplify any salmonellae present, and DNA was isolated from the resulting biomass. One hundred one samples (11.8%) were shown to contain Salmonella enterica using the real-time PCR assay, whereas conventional culture techniques detected the pathogen in only 22 (2.6%) of the samples. A conventional PCR assay targeting a different gene from Salmonella enterica confirmed the presence of the organism in 94 of the real-time PCR-positive samples. Thus, assay of milk samples by real-time PCR indicates that the prevalence of Salmonella enterica in US bulk tank milk is substantially higher than previously reported.


[SERODIAGNOSIS OF THE MYCOBACTERIUM AVIUM COMPLEX BY USING IgA ANTIBODIES FOR THE GLYCOPEPTIDOLIPID CORE ANTIGEN].
The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) can be challenging. A serodiagnosis enzyme immunoassay (EIA) kit, which detects the serum anti-glycopeptidolipid (GPL) core IgA antibody, has been commercialized recently; however, its clinical usefulness in the diagnosis of MAC-PD is still unclear. This study aimed to evaluate the availability of this kit and identify factors affecting testing accuracy. We performed a retrospective study of 195 patients who were evaluated with an EIA kit at Nagasaki University Hospital between November 2012 and March 2014. 12 of 16 (75.0%) MAC patients have underlying diseases ; 8 of 16 (50%) had complications associated with respiratory diseases. There were no significant differences between the seropositive and seronegative background of patients with confirmed MAC-PD. Regarding the accuracy of serodiagnosis EIA kit, its sensitivity and specificity were 81.3% and 88.3% (with a cut-off value of 0.7 U/ml), respectively. Of false-positive patients with bronchiectasis, 28.6 % demonstrated a good response to anti-MAC treatment, indicating that the sensitivity of the EIA kit might be higher than that of culture-based diagnosis because patients with clinically diagnosed MAC-PD were included in the false-positive population. In the current study, the serodiagnosis EIA kit demonstrated good sensitivity and specificity for the diagnosis of MAC-PD. Further clinical investigations are necessary to clarify the role of this kit in definitively diagnosing MAC infections.


Edge-differentiating deposition of Co on SiO(2)-supported MoS(2) particles.
The chemical vapor deposition of Co(CO)(3)NO under controlled conditions onto MoS(2) catalysts supported on SiO(2) achieves the edge-differentiating deposition of Co between (1010) and (1010) edges of MoS(2) particles, the former edge being preferentially decorated by Co at a low Co content to form a catalytically "active" structure for hydrodesulfurization.


Analysis of Benthic Communities in the Cyclades Plateau (Aegean Sea) Using Ecological and Paleoecological Data Sets.
In the Cyclades plateau (Aegean Sea), a qualitative and quantitative analysis of macro-benthic fauna was carried out in 1986. Standard multivariate analysis techniques were applied to both ecological (living benthic fauna) and paleoecological data sets in order to distinguish distribution patterns. Results showed that caution must prevail in drawing conclusions from a limited data set. The clearest classification was obtained using total living fauna, while the dead molluscan fauna gave a similar pattern; this indicates similar response to the environmental conditions of the area. In the analysis of the living molluscan fauna, the groups failed to show any clusters, probably as an effect of some impoverished sites. In the two groups delineated, depth seems to be the major factor in the distribution of species. The fact that two distinct data sets (subfossil assemblages and living communities), when treated separately, produce similar grouping indicates that the subfossil assemblages could be reliably used as a first approach for determination of the living communities' distribution patterns.


Facile design and nanostructural evaluation of silver-modified titania used as disinfectant.
Fundamental research has been carried out to define optimal "green" synthesis conditions for the production of titania (TiO(2)) and silver (Ag) nanocomposites (TANCs) ranging from 12.7-22.8 nm in diameter. A bottom-up colloidal approach was employed to accurately control TANC monodispersity and composition. TANCs were found to be effective at inactivating Escherichia coli (E. coli) in water. The presence of Ag in the nanocomposites induced a decrease in TiO(2) band gap energy, which favoured valence to conduction band electron transfer and allowed for electron excitation using visible light. Aggregation of ultra-fine particles was prevented through the use of a long-chain polymer as evidenced by electrophoretic mobility studies. The TANCs catalyzed oxidation of bacterial membranes and cell death or disinfection. Theoretically, the TANC mode of E. coli disinfection is via water photolysis, which results in production of hydroxyl radicals and hydrogen peroxide. These interact with the outer membrane polysaccharides and lipids, leading to lipid peroxidation, membrane weakening and resulted in cell death. Our overarching goals were to optimize the variables involved in TANC "green" synthesis and to characterize its nanostructure. High resolution (HR) transmission and scanning electron microscopic (TEM and SEM) studies demonstrated that TANCs were highly crystalline and mono-dispersive. Elemental composition of Ag and Ti, as measured by X-ray energy dispersive (EDS) and X-ray photoelectron spectroscopy (XPS) confirmed sample purity. Ultraviolet-visible (UV-VIS) spectroscopy showed that the energy band-gap of Ag modified TiO(2) was in the visible range.


Renal colic: the role of ultrasound in initial evaluation.
A prospective sonographic study of 21 patients with suspected renal colic was undertaken to detect the presence or absence of urinary tract calculi. The presence of calculi was diagnosed sonographically by visualization of the calculus and/or unilateral hydronephrosis in all 18 cases in which presence of a calculus was subsequently proved by surgery, spontaneous passage and recovery, or intravenous urography. In the two cases in which the sonographic examination demonstrated neither calculi nor unilateral obstruction, further evaluation confirmed the absence of calculi. There was one false-positive examination in which unilateral hydronephrosis was detected secondary to a retroperitoneal tumor. There were no false-negative examinations. The results of this study support the use of ultrasound in the initial evaluation of renal colic.


Clostridium difficile isolation in neonates in a special care unit. Lack of correlation with necrotizing enterocolitis.
The stools of 78% of 45 infants in a Special Care Baby Unit yielded Clostridium difficile on culture, and in 67% of these it was possible to detect C. difficile toxin by means of a tissue culture technique. The stools of six of the seven infants with necrotizing enterocolitis were positive for C. difficile, but neither of the two most severely affected contained C. difficile toxin. The incidence of C. difficile isolation was similar in infants treated by exchange transfusion, those treated with antibiotics, those of low birth weight, and those with respiratory distress. The serum of only 2 of 28 infants and 1 of 20 mothers contained a neutralizing factor to C. difficile toxin. The present study does not support a role for C. difficile in neonatal disorders and in particular necrotizing enterocolitis. The reason for the apparent tolerance of the neonatal bowel to C. difficile toxin remains to be explained.


Fracture investigation in starch-based foods.
The study of oral processing and specifically cutting of the food piece during mastication can lead towards optimization of products for humans or animals. Food materials are complex biocomposites with a highly nonlinear constitutive response. Their fracture properties have not been largely investigated, while the need for models capable of predicting food breakdown increases. In this study, the blade cutting and the essential work of fracture (EWF) methodologies assessed the fracture behaviour of starch-based pet food. Tensile tests revealed rate-dependent stiffness and stress softening effects, attributed to viscoplasticity and micro-cracking, respectively. Cutting data were collected for 5, 10 and 30 mm s(-1) sample feed rates, whereas the EWF tests were conducted at 1.7, 3.3 and 8.3 mm s(-1) crosshead speeds corresponding to average crack speeds of 4, 7 and 15 mm s(-1), respectively. A reasonable agreement was achieved between cutting and EWF, reporting 1.26, 1.78, 1.76 kJ m(-2) and 1.52, 1.37, 1.45 kJ m(-2) values, respectively, for the corresponding crack speeds. These toughness data were used in a novel numerical model simulating the 'first' bite mastication process. A viscoplastic material model is adopted for the food piece, combined with a damage law that enabled predicting fracture patterns in the product.


Natural infection of Nyssomyia neivai by Leishmania (Viannia) spp. in the state of Paraná, southern Brazil, detected by multiplex polymerase chain reaction.
Natural sandfly infection by Leishmania spp. in an area endemic for American cutaneous leishmaniasis was analyzed using multiplex polymerase chain reaction (PCR). The sandflies were captured using Falcão light traps in an endemic area of the municipality of Doutor Camargo during March, April, and June 2008. In total, 1803 females were analyzed; 1755 were Nyssomyia neivai (Pinto) and 48 were Nyssomyia whitmani (Antunes and Coutinho). Multiplex PCR analyses using MP3H-MP1L and 5Llcac-3Llcac primers showed the presence of Leishmania (Viannia) spp. in 4/181 pools of sandflies, all Ny. neivai, that is, a minimal infection rate of 0.22%. This study showed, for the first time, the presence of DNA of Leishmania (Viannia) spp. in Ny. neivai. This suggests the existence of natural infection by Leishmania (Viannia) spp. in Ny. neivai in the state of Paraná. Multiplex PCR is an important tool in the detection of Leishmania infection in sandflies.


Mediating Role of Mental Resilience between Sleep Quality and Mindfulness Level of Pregnant Women Screened by Prenatal Diagnosis.
To explore the status quo of psychological resilience, mindfulness level, the sleep quality of pregnant women by Prenatal Diagnosis Screening, and the mediating effect of psychological resilience on sleep quality and mindfulness. A survey of 298 pregnant women was conducted using the psychological resilience scale, Pittsburgh sleep quality index, and the concise version of the five-factor mindfulness scale. The total score of psychological resilience of pregnant women was (68.96 ± 17.27), mindfulness was (77.25 ± 12.65), the median of total sleep quality was 6, and the detection rate of sleep disorders was 31.9%. The sleep quality of pregnant women was negatively correlated with mindfulness level and psychological resilience (p < 0.01), and mindfulness level was positively associated with psychological resilience (p < 0.01). Bootstrap analysis showed that psychological resilience played an 14.1% mediating role between mindfulness and sleep quality. The psychological resilience of pregnant women is low, sleep quality is poor, and mindfulness is mild to moderate. Psychological resilience plays an important role in mediating between mindfulness level and sleep quality that suggests nursing staff should pay attention to and improve the psychological resilience of pregnant women screened by prenatal diagnosis to improve the mindfulness level and sleep quality of pregnant women screened by prenatal diagnosis.


Pro-IGF2-induced hypoglycaemia associated with hepatocellular carcinoma.
We present a patient (87 years, female) who was admitted to the emergency department because of loss of consciousness. Previous medical history included advanced-stage hepatocellular carcinoma and associated weight loss. She was found on the ground in an unresponsive state by her daughter and was determined to be hypoglycaemic. Upon bolus administration of 100 mL intravenous glucose (10%), glucose levels increased to 2.9 mmol/L and the patient regained full consciousness. She was admitted to the hospital for further examination, and treatment and continuous intravenous glucose infusion was initiated. As the patient was known to suffer from advanced-stage hepatocellular carcinoma, tumour-associated hypoglycaemia was suspected. Insulin, c-peptide and IGF1 concentrations were indeed low, cortisol concentration was high and IGF2 and Pro-IGF2 were borderline low and borderline high normal respectively. IGF2:IGF1 ratio was 23, confirming the diagnosis of non-islet cell tumour hypoglycaemia. During the initial phase of treatment, euglycaemia was maintained by continuous variable glucose infusion (5%, varying between 1 and 2 L/24 h), and the patient was advised to eat small snacks throughout the day. After euglycaemia was established and the diagnosis was confirmed, prednisolone was started (30 mg, 1 dd) and glucose infusions were halted. Under prednisolone treatment, glucose levels were slightly increased and no further hypoglycaemic episodes occurred. At her request, no surgery was performed. After 19 days, the patient was discharged to a hospice and died 3 weeks later. Hepatocellular carcinoma may be associated with non-islet cell tumour hypoglycaemia (NICTH).NICTH-induced hypoglycaemia is associated with low insulin and IGF1.Measurement of IGF2 only (without measurement of Pro-IGF2 and IGF1) may be insufficient to prove NICTH.


Letter and category fluency in patients with frontal lobe lesions.
This study examines the hypothesis that patients with frontal lobe lesions are impaired on tests of letter but not category fluency. This hypothesis was proposed by Moscovitch (1994), based on a series of cognitive studies with young, normal participants. A group of patients with lateral prefrontal lesions and age-matched controls were tested on 2 tests of verbal fluency, the FAS task and a category fluency task that used semantic categories as cues (e.g., animals). Patients with frontal lobe lesions generated fewer items than controls on both letter and category fluency. This effect did not interact with the type of fluency test, suggesting that the frontal lobes are more generally involved in verbal fluency. Moreover, this pattern of findings, along with previous results of impaired free recall and remote retrieval in this patient group, suggests that patients with frontal lobe lesions do not efficiently organize and develop retrieval strategies.


Analysis and application of neuronal network controllability and observability.
Controllability and observability analyses are important prerequisite for designing suitable neural control strategy, which can help lower the efforts required to control and observe the system dynamics. First, 3-neuron motifs including the excitatory motif, the inhibitory motif, and the mixed motif are constructed to investigate the effects of single neuron and synaptic dynamics on network controllability (observability). Simulation results demonstrate that for networks with the same topological structure, the controllability (observability) of the node always changes if the properties of neurons and synaptic coupling strengths vary. Besides, the inhibitory networks are more controllable (observable) than the excitatory networks when the coupling strengths are the same. Then, the numerically determined controllability results of 3-neuron excitatory motifs are generalized to the desynchronization control of the modular motif network. The control energy and neuronal synchrony measure indexes are used to quantify the controllability of each node in the modular network. The best driver node obtained in this way is the same as the deduced one from motif analysis.


Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: A COMPERA analysis.
Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed CTD (MCTD), undifferentiated CTD (UCTD), and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERA), phosphodiesterase type 5 inhibitors (PDE5i), or a combination of these two drug classes. This analysis included 607 patients with CTD-PAH. Survival estimates at 1-, 3- and 5-years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34), 97%, 77% and 61%; for MCTD-PAH (n = 33), 97%, 70% and 59%, for UCTD (n = 60), 88%, 67%, and 52%; and for other CTD (n = 90), 92%, 69%, and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (p= 0.001). In these patients, the survival estimates were significantly better with initial ERA/PDE5i combination therapy than with initial ERA or PDE5i monotherapy (p= 0.016 and p= 0.012, respectively). Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA/PDE5i combination therapy compared with initial monotherapy.


Multiscale analysis of Benjamin Franklin's innovations in American paper money.
Benjamin Franklin was a preeminent proponent of the new colonial and Continental paper monetary system in 18th-century America. He established a network of printers, designing and printing money notes at the same time. Franklin recognized the necessity of paper money in breaking American dependence on the British trading system, and he helped print Continental money to finance the American War of Independence. We use a unique combination of nondistractive, microdestructive, and advanced atomic-level imaging methods, including Raman, Infrared, electron energy loss spectroscopy, X-ray diffraction, X-ray fluorescence, and aberration-corrected scanning transmission electron microscopy, to analyze pre-Federal American paper money from the Rare Books and Special Collections of the Hesburgh Library at the University of Notre Dame. We investigate and compare the chemical compositions of the paper fibers, the inks, and fillers made of special crystals in the bills printed by Franklin's printing network, other colonial printers, and counterfeit money. Our results reveal previously unknown ways that Franklin developed to safeguard printed money notes against counterfeiting. Franklin used natural graphite pigments to print money and developed durable "money paper" with colored fibers and translucent muscovite fillers, along with his own unique designs of "nature-printed" patterns and paper watermarks. These features and inventions made pre-Federal American paper currency an archetype for developing paper money for centuries to come. Our multiscale analysis also provides essential information for the preservation of historical paper money.


Analysis of Tc1-Mariner elements in Sclerotinia sclerotiorum suggests recent activity and flexible transposases.
Sclerotinia sclerotiorum is a necrotrophic fungus that is pathogenic to many plants. Genomic analysis of its revealed transposable element expansion that has strongly influenced the evolutionary trajectory of several species. Transposons from the Tc1-Mariner superfamily are thought to be ubiquitous components of fungal genomes and are generally found in low copy numbers with large numbers of deleterious mutations in their transposase coding sequence. This study shows that the genome of S. sclerotiorum has a large number of copies of Tc1-Mariner transposons, and in silico analysis shows evidence that they were recently active. This finding was confirmed by expressed sequence tag (EST) analysis. Fourteen new Tc1-Mariner transposon families that were distributed throughout the genome were identified, and in some cases, due to the excision/retention of introns, different transcripts were observed for the same family, which might be the result of an efficient strategy to circumvent mutations that generate premature stop codons in the RNA sequence. In addition, the presence of these introns shows that the transposase protein has a flexible coding sequence and, consequently, conformation. No evidence for RIP-like gene silencing mechanisms, which are commonly found in fungi, was found in the identified Tc1-Mariner elements, and analysis of the genomic insertion sites of these elements showed that they were widely distributed throughout the genome with some copies located near the 3' regions of genes. In particular, EST analysis demonstrated that one of these copies was co-expressed with a gene, which showed the potential for these elements to undergo exaptation. Fourteen novel Tc1-Mariner families were characterized. Some families had evidence of introns, which might or might not be excised depending on the family or element in question, and this finding demonstrates a possible strategy for overcoming possible mutations that generate premature stop codons in a RNA sequence. Tc1-Mariner elements likely play an important role in the structure and evolution of the S. sclerotiorum genome.


FOXA1 prolongs S phase and promotes cancer progression in non-small cell lung cancer through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.
Non-small cell lung cancer (NSCLC) causes high mortality worldwide; however, its molecular pathways have not been fully investigated. The relationship between FOXA1 and CDC5L as well as their roles in NSCLC have not been comprehensively studied. Clinical tissues were collected from 78 NSCLC patients for clinical studies. The BEAS-2B human normal lung epithelial cell line and the A549, Calu-3, H526 and H2170 human NSCLC cell lines were used for in vitro studies. sh-FOXA1 and oe-CDC5L constructs were used to generate knockdown and overexpression models, respectively. The CCK-8 assay was used to analyze cell viability. The cell cycle and apoptosis were evaluated by flow cytometry analysis. The relationship between FOXA1 and CDC5L was demonstrated using dual-luciferase and ChIP assays. Gene levels were examined via immunohistochemistry, qRT-PCR and western blot analysis. FOXA1 levels were increased in NSCLC clinical tissues and cell lines. Depletion of FOXA1 increased the apoptosis rate and increased the proportion of cells in G2/M phase. In addition, we demonstrated that FOXA1 was directly bound to the promoter of CDC5L and that depletion of FOXA1 inhibited CDC5L expression. Overexpression of CDC5L induced ERK1/2 phosphorylation, induced JAK2 phosphorylation, inhibited cell apoptosis, prolonged S phase, and significantly reversed the effects of FOXA1 knockdown on the progression of NSCLC. The present study demonstrated that FOXA1 prolongs S phase and promotes NSCLC progression through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.


Chlorine dioxide oxidation of Escherichia coli in water - A study of the disinfection kinetics and mechanism.
This study investigated the kinetics and mechanism of chlorine dioxide (ClO2) inactivation of a Gram-negative bacteria Escherichia coli (ATCC 35218) in oxidant demand free (ODF) water in detail as a function of disinfectant concentration (0.5-5.0 mg/L), water pH (6.5-8.5), temperature variations (4-37°C) and bacterial density (105-107 cfu/mL). The effects of ClO2 on bacterial cell morphology, outer membrane permeability, cytoplasmic membrane disruption and intracellular enzymatic activity were also studied to elucidate the mechanism of action on the cells. Increasing temperature and disinfectant concentration were proportional to the rate of cell killing, but efficacy was found to be significantly subdued at 0.5 mg/L and less dependent on the bacterial density. The bactericidal efficiency was higher at alkaline pH of 8 or above as compared to neutral and slightly acidic pH of 7 and 6.5 respectively. The disinfection kinetic curves followed a biphasic pattern of rapid inactivation within the initial 2 min which were followed by a tailing even in the presence of residual biocide. The curves were adequately described by the Cavg Hom model. Transmission Electron Microscopy images of the bacteria cells exposed to lethal concentrations of ClO2 indicated very little observable morphological damage to the outer membranes of the cells. ClO2 however was found to increase the permeability of the outer and cytoplasmic membranes leading to the leakage of membrane components such as 260 nm absorbing materials and inhibiting the activity of the intracellular enzyme β-D-galactosidase. It is suggested that the disruption of the cytoplasmic membrane and subsequent efflux of intracellular components result in the inactivation of the Gram-negative bacteria.


Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis.
Hereditary elliptocytosis (HE) Sp alpha I/74 is a disorder associated with defective spectrin (Sp) heterodimer self-association and an abnormal tryptic cleavage of the 80-kD alpha I domain of Sp resulting in increased amounts of a 74-kD peptide. The molecular basis of this disorder is heterogeneous and mutations in codons 28, 46, 48, and 49 (codons 22, 40, 42, and 43 in the previous nomenclature which did not include the six NH2-terminal amino acids) have been reported. In this study we present data on seven unrelated HE Sp alpha I/74 kindred from diverse racial backgrounds in whom we identified four different mutations all occurring in exon 2 of alpha Sp at codon 28. Utilizing the polymerase chain reaction we established a CGT----CTT; Arg----Leu 28 mutation in one kindred of Arab/Druze origin. In two unrelated white kindred of English/European origin the substitution is CGT----AGT; Arg----Ser 28 and in two apparently unrelated white kindred from New Zealand, the mutation is CGT----TGT; Arg----Cys 28. Finally, in one American black kindred and in a black kindred from Ghana the mutation involves CGT----CAT; Arg----His 28. Allele specific oligonucleotide hybridization confirmed that the probands are heterozygous for the respective mutant alleles. All four point mutations abolished an Aha II restriction enzyme site which allowed verification of linkage of the mutation with HE Sp alpha I/74. Our results imply that codon 28 of alpha Sp is a "hot spot" for mutations and also indicate that Arg 28 is critical for the conformational stability and functional self association of Sp heterodimers.


Porous poly (D,L-lactide-co-glycolide) acid/biosilicate® composite scaffolds for bone tissue engineering.
This study evaluated the effects of the Biosilicate® and poly (D,L-lactic-co-glycolic) acid composites on bone repair in a tibial bone defect model in rats by means of using histological evaluation (histopathological and morphometric analysis) and gene expression analysis. Eighty male Wistar rats (12 weeks old, weighing ±300 g) were randomly divided into two groups: Biosilicate® group (BG) and Biosilicate® /PLGA group (BG/PLGA). Each group was euthanized at 3, 7, 14, and 21 days after surgery (n = 10 animals per time point). The main findings showed that the incorporation of PLGA into BG had a significant effect on the morphological structure of the material, accelerating mass loss, decreasing the pH and increasing the calcium release. Furthermore, histologic analysis revealed that the BG/PLGA showed increased material degradation, accompanied by higher bone formation compared to BG, after 21 days of implantation. In addition, qRT-PCR analysis showed that BG/PLGA induced an upregulation of the osteogenic genes related to BMP4, Runx2, ALP, and OC. These results show that the present BG/PLGA composite may be used as a bone graft for inducing bone repair. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 63-71, 2017.


Immunohistochemical diagnosis of prostatic cancer with metastasis.
An immunohistochemical method for detecting prostatic acid phosphatase is described for the diagnosis of metastatic prostatic carcinoma. The specific antiserum against prostatic acid phosphatase was prepared from rabbit by injection of acid phosphatase purified from seminal fluid. This method gives a selective staining of the cytoplasm of the glandular epithelial cells of prostatic tissue specimens on paraffin section. Most of the non-prostatic tissues were negative except for occasional weak staining in granulocytes, islet cells of pancreas, parietal cells of stomach, tubular epithelial cells of kidney, and liver cells. Also examined were 50 consecutive cases of metastatic tumor involving the bone marrow and 5 cases of metastatic prostatic carcinoma involving the lymph node or lung. All 20 cases with prostatic primary lesion showed positive staining. All other cases were negative, except 5 of the 14 cases of metastatic breast carcinoma in women showing weakly positive results. The method is fairly specific for identification of metastatic prostatic carcinoma. Occasional positive staining in breast tumor needs further study to establish whether the staining is due to the same isoenzyme or to certain cross immunoreactivity.


Evaluation of healing by gentle touch.
To evaluate the effectiveness and safety of healing by gentle touch in clients attending The Centre for Complementary Care (CCC) in Eskdale, Cumbria. An evaluation of data collected by questionnaire over 6 years. All clients attending the CCC between 1995 and 2001 were invited to participate in this study, and data were collected from 300 subjects with a wide range of ailments who received four treatment sessions within 6 weeks. Exclusion criteria were: recent treatment at the CCC; failure to complete four treatment sessions; and age under 16 years. Outcome measures included comparison of pre- and post-treatment levels of physical (pain, disability, immobility, sleep disturbances, reliance upon medication, daily activities) and psychological (stress, panic, fear, anger, relaxation, coping, depression/anxiety) functioning; these were assessed using a questionnaire with visual analogue scales for subjective rating of symptoms and the EuroQoL (EQ-5D), a generic state-of-health measure. Wilcoxon signed ranks tests showed statistically significant improvements in both psychological and physical functioning, particularly in stress reduction (median stress levels fell by four points), pain relief (median pain ratings fell by two points), increased ability to cope (median improvement of three points) and increased general health ratings (median improvement of 20 points) between study entry and end of treatment (P < 0.0004 for all these symptoms). The most substantial improvements were seen in those with the most severe symptoms at study entry. No adverse effects of treatment were documented. This audit of treatment outcomes provides evidence consistent with the hypothesis that healing, as provided at the CCC, was associated with improved psychological and physical functioning in the majority of subjects, and is worthy of further evaluation.


Can Coinage Metal Atoms Be Capable of Serving as an Excess Electron Source of Alkalides with Considerable Nonlinear Optical Responses?
Alkalides, as a representative kind of excess electron compounds, have been demonstrated to be potential nonlinear optical (NLO) materials with large static first hyperpolarizabilities (β0). The possibility of utilizing coinage metal atoms as a novel excess electron source to design a series of alkalides, i.e., (M@36adz)M' (M = Cu, Ag, and Au; M' = Li, Na, and K), was examined by density functional theory calculations. The alkalide characteristics of these compounds are guaranteed by their HOMOs and VIE values as well as NBO analysis. In particular, all proposed alkalides exhibit considerable first hyperpolarizabilities (β0) up to 61 590 au, indicating that they can be considered as novel NLO molecules of high performance. Moreover, a larger cage-complexant has been considered, and the resulting (Ag+@TriPip222)K- alkalide possesses a remarkably large β0 value of 180 068 au. We hope that this work will provide a new recipe for designing excess electron compounds and, on the other hand, attract more research interest and efforts in exploring new, unconventional alkalides.


Relationship of 2',3'-cyclic nucleotide 3'-phosphohydrolase activity of large enveloped RNA viruses to host cell activity.
Purified virions of the large RNA viruses show 2',3'-cyclic nucleotide 3'-phosphohydrolase (3'-CNPase) activity. The 3'-CNPase activity is virion-associated and stimulated by their treatment with nonionic detergents. Cytopathic viruses such as influenza A2 (Singapore/57), NDV, and VSV showed the specific activity of a virion-associated 3'-CNPase equal to or lower than the specific activity of host cell enzyme. Retroviruses are an example of extreme relationship of 3'-CNPase to virion. With the AMV-BAI-A associated enzyme activity increased after Triton X-100 treatment ten times more than that associated with other viruses examined. The specific activity of virus-associated 3'-CNPase was 16-28 times higher than that in chick myeloblasts. BLV showed a very low enzyme activity. The correlation between the activity of cellular 3'-CNPase and virus yield showed that 3'-CNPase could belong to cellular factors influencing virus replication.


Evidence for flexibility in the function of ribonuclease A.
The dynamic properties of the enzyme ribonuclease A (RNase A) were investigated through the use of solution NMR spin relaxation experiments. As determined by "model-free" analysis, RNase A is conformationally rigid on time scales faster than overall rotational tumbling (picoseconds to nanoseconds). The average order parameter, S(2), for RNase A is 0.910 +/- 0.051. However, 28 of the amino acid residues in RNase A were identified as undergoing chemical exchange on the microsecond to millisecond time scale. For 16 of these residues the microscopic chemical exchange rates, k(ex), were quantitated through the use of the relaxation-compensated CPMG (rcCPMG) experiment. The value of k(ex) was identical for all residues with an average of 1640 s(-1) and is similar to the RNase A k(cat) value of 1900 s(-1). Many of these mobile residues localize to the active site in RNase A and include the catalytically crucial amino acids His119 and Asp121. Additional motion is found in the B1, B2, and P0 subsites, suggesting a coupling of motion between the binding and catalytic sites. The activation energy of the observed millisecond motion was measured by applying the rcCPMG experiment at temperatures of 283, 293, and 298 K and was determined to vary between 3.6 and 7.4 kcal/mol. The measured barrier to conformational motion is similar to the activation barrier for the RNase A catalyzed reaction and thus would not be thermodynamically limiting to catalysis. These studies suggest a correlation of conformational exchange kinetics and thermodynamics derived from NMR measurements with those determined by biochemical means and are suggestive of an important role for flexibility in enzyme function.


A reappraisal of the indications for laparoscopic treatment of adrenal metastases.
Laparoscopic adrenalectomy (LA) is unanimously recognized as the gold standard for the surgical treatment of adrenal lesions, but when to remove malignant lesions by this approach still remains controversial. We reviewed all cases of LA for suspected adrenal metastases carried out in our hospital, trying to focus on what should be the ideal preoperative workup, so as to avoid unnecessary operations. The possible role of fine needle aspiration biopsy (FNAB) in selecting patients was evaluated. Twenty-two patients underwent LA for suspected adrenal metastases from May 1994 to March 2003. Primary tumors were from lung in 14 cases, colon in 2 cases, kidney in 3 cases, thyroid in 2 cases, and breast in 1 case. LA was successfully performed in all but three cases. In 13 patients, 14 FNAB were performed: 8 cases proved to be true positive, 4 true negative, and 2 false negative. Final histology showed 6 cortical adenomas. Local relapse was present only in one patient, who died after 14 months. Of the metastatic patients, 8 are alive and free of disease after a mean followup of 39 months. The most accurate workup is of the greatest importance in order to avoid unnecessary surgery for suspected adrenal metastases. The absence of false positives (FP) and the fairly high number of true positives (TP) does not justify the effort of performing FNAB routinely. Indeed, laparoscopic exploration, being simple and quick, allows optimal diagnosis at a low cost, even when histological definition cannot be obtained.


Triple Threat: Triple-Valve Endocarditis Case Report and Literature Review.
Triple valve endocarditis (TVE) is a rare presentation of endocarditis often requiring multivalvular surgery. Here we report a case of S. aureus triple valve endocarditis in a patient with a history of intravenous drug use and provide a literature review of TVE identification, treatment, and prognosis.


Perceived Maternal Behavioral Control, Infant Behavior, and Milk Supply: A Qualitative Study.
Disparities persist in breastfeeding exclusivity and duration despite increases in breastfeeding initiation. The objective of this study was to examine factors that influence maternal decision making surrounding infant feeding practices over time in a diverse inner-city population. We conducted a prospective qualitative study with 20 mothers recruited from 2 urban primary care clinics. Participants completed open-ended interviews and demographic questionnaires in English or Spanish administered at approximately 2 weeks and 6 months postpartum. Transcripts were analyzed using a combined technique of inductive (data-driven) and deductive (theory-driven, based on the Theory of Planned Behavior) thematic analysis using 3 independent coders and iterative discussion to reach consensus. All women initiated breastfeeding, and 65% reported perceived insufficient milk (PIM). An association between PIM and behavioral control emerged as the overarching theme impacting early breastfeeding cessation and evolved over time. Early postpartum, PIM evoked maternal distress-strong emotional responses to infant crying and need to control infant behaviors. Later, mothers accepted a perceived lack of control over milk supply with minimal distress or as a natural process. Decisions to stop breastfeeding occurred through an iterative process, informed by trials of various strategies and observations of subsequent changes in infant behavior, strongly influenced by competing psychosocial demands. Infant feeding decisions evolve over time and are influenced by perceptions of control over infant behavior and milk supply. Tailored anticipatory guidance is needed to provide time-sensitive strategies to cope with challenging infant behaviors and promote maternal agency over breastfeeding in low-income populations.


[Positron emission tomography (PET) in diagnosis and therapy planning of malignant lymphoma].
The management of patients who have malignant lymphomas requires functional methods to differentiate residual soft tissue masses. Positron emission tomography (PET) was performed in patients with histologically proven malignant lymphomas prior to the onset of second-line chemotherapy to examine tumor viability. Twenty patients (68 malignant lesions and 3 benign lesions) with Hodgkin lymphomas (HL) as well as 26 patients (46 malignant lesions and 1 benign lesion) with non-Hodgkin lymphomas (NHL) were studied with fluorine-18-deoxyglucose (FDG). Oxygen-15-labelled water was used in addition in 14 patients with 25 lesions to obtain information on the tissue perfusion. PET with FDG is highly sensitive for the detection of viable tumor tissue, all malignant lesions being correctly classified in this study. We noted no statistically significant difference in FDG metabolism for Hodgkin and non-Hodgkin lymphomas. Even normal-sized lymph-node metastases (< 1 cm) were detected with PET and FDG. The possible limitations are inflammatory processes, which may obscure tumor detection because of the increased FDG uptake, as well as malignant lesions with low FDG uptake as a result of reduced perfusion. Comparison of tumor perfusion and FDG uptake showed a significant nonlinear correlation of r = 0.78 between the two parameters. Two patients with scar tissue and no evidence of malignancy were excluded from blood stem-cell support therapy as a result of the PET study. The data demonstrate that PET is a useful tool for making a diagnosis and deciding on therapy for malignant lymphomas.


Decision making in clinical trials: Interim analyses, innovative design, and biomarkers.
The efficient and accurate execution of clinical trials testing novel treatments for Alzheimer's disease (AD) is a critical component of the field's collective efforts to develop effective disease-modifying treatments for AD. The lengthy and heterogeneous nature of clinical progression in AD contributes to the challenges inherent in demonstrating a clinically meaningful benefit of any potential new AD therapy. The failure of many large and expensive clinical trials to date has prompted a focus on optimizing all aspects of decision making, to not only expedite the development of new treatments, but also maximize the value of the information that each clinical trial yields, so that all future clinical trials (including those that are negative) will contribute toward advancing the field. To address this important topic the Alzheimer's Association Research Roundtable convened December 1-2, 2020. The goals focused around identifying new directions and actionable steps to enhance clinical trial decision making in planned future studies.


The effect of Silicon on photosynthesis and expression of its relevant genes in rice (Oryza sativa L.) under high-zinc stress.
The main objectives of this study were to elucidate the roles of silicon (Si) in alleviating the effects of 2 mM zinc (high Zn) stress on photosynthesis and its related gene expression levels in leaves of rice (Oryza sativa L.) grown hydroponically with high-Zn stress. The results showed that photosynthetic parameters, including net photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2 concentration, chlorophyll concentration and the chlorophyll fluorescence, were decreased in rice exposed to high-Zn treatment. The leaf chloroplast structure was disordered under high-Zn stress, including uneven swelling, disintegrated and missing thylakoid membranes, and decreased starch granule size and number, which, however, were all counteracted by the addition of 1.5 mM Si. Furthermore, the expression levels of Os08g02630 (PsbY), Os05g48630 (PsaH), Os07g37030 (PetC), Os03g57120 (PetH), Os09g26810 and Os04g38410 decreased in Si-deprived plants under high-Zn stress. Nevertheless, the addition of 1.5 mM Si increased the expression levels of these genes in plants under high-Zn stress at 72 h, and the expression levels were higher in Si-treated plants than in Si-deprived plants. Therefore, we conclude that Si alleviates the Zn-induced damage to photosynthesis in rice. The decline of photosynthesis in Zn-stressed rice was attributed to stomatal limitation, and Si activated and regulated some photosynthesis-related genes in response to high-Zn stress, consequently increasing photosynthesis.


Critical role of inducible costimulator signaling in the development of arteriosclerosis.
Proliferation and migration of smooth muscle cells (SMCs) and migration and accumulation of monocytes and T cells are landmark events in the development of arteriosclerosis. SMC proliferation in the intima induces interruption of blood flow and results in ischemia and graft rejection. Inducible costimulator (ICOS) is a major costimulator of T cell activation. However, the effect of costimulatory molecules on the formation of neointimal hyperplasia has not been fully elucidated. We examined the role of the ICOS pathway in SMC proliferation. ICOS ligand (ICOSL) was detected in SMCs stimulated by interleukin (IL)-1beta, and coculture of stimulated SMCs and activated T cells induced SMC proliferation. Inhibition of the ICOS pathway resulted in inhibition of SMC proliferation. In models of transplantation and vascular injury, ICOSL was induced in SMCs in the neointima. Expression of IL-1beta, a key inducer of ICOSL expression, was significantly reduced in mice treated with anti-ICOS antibody or soluble form of ICOS (ICOSIg) and in ICOS-deficient mice. Inhibition of the ICOS pathway significantly suppressed neointimal thickening. These results indicate that ICOS on activated T cells contributes to neointimal formation through the regulation of SMC proliferation. These findings provide insights into new therapeutic strategies for arteriosclerosis.


Plasma cell granuloma of the oral cavity: a report of two cases and review of the literature.
We report two rare cases of plasma cell granuloma arising in the extragingival oral cavity. These are tumorous proliferations composed predominantly of reactive plasma cells. Both patients presented with solitary mass lesions that were clinically suspicious for malignancy. One patient presented with a mass that grew slowly for 2 years and involved the lip; in the second patient, a mass developed in the buccal mucosa Histologically, both lesions were characterized by lobules of plasma cells separated by thick collagenous bands. A variable number of admixed lymphocytes and histiocytes was noted in both cases. In situ hybridization and immunostaining for kappa and lambda light chains revealed a polyclonal plasma cell population. In situ hybridization for Epstein-Barr virus failed to demonstrate evidence of viral expression in either case. Both patients are free of disease after 8-month and 12-month follow-ups. Although plasma cell granuloma in the oral cavity is rare, it is important to recognize this entity as a benign inflammatory lesion.


First and stereoselective synthesis of an α-(2→5)-linked disaccharide of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo).
Resistance of bacterial pathogens toward antibiotics has revived interest in lipopolysaccharide (LPS) motifs as potential therapeutic targets. The LPS of several pathogenic Acinetobacter strains comprises a 4,5-branched Kdo trisaccharide containing an uncommon (2→5)-linkage. In this contribution the first stereoselective glycosylation method for obtaining an α-Kdo-(2→5)-α-Kdo disaccharide in good yield is highlighted. The synthetic approach used for accessing this linkage type will allow for future studies of the immunoreactivity associated with this unique bacterial Kdo inner core structure.


Physiopathology of primary periodontitis associated with plaque. Microbial and host factors. A review. Part 1.
Microbial factors involved in the genesis of periodontitis include colonization, bacterial penetration of the epithelium, multiplication and invasive-destructive capacity. Colonization of the gingival sulcus is related, to a certain extent, to supragingival plaque. Bacterial multiplication is induced by nutrients in the gingival fluid, and nutrients produced by degradative and excretory microbial activity. Invasion and destruction are mediated by exotoxins, structural elements of the bacteria, enzymes, metabolites, polyclonal lymphocyte activity, fibroblastic cytotoxicity, and leukocyte chemotactic inhibition.


Agenesis of third molar germs depends on sagittal maxillary jaw dimensions in orthodontic patients in Japan.
The aim of this study was to determine the correlation between congenitally missing third molar tooth germs and sagittal maxillomandibular jaw dimensions in orthodontic patients in Japan. The subjects were 391 patients from the orthodontic clinic of the Hokkaido University Dental Hospital who were less than 15 years of age. Assessments were made from panoramic radiographs and lateral cephalograms. The subjects were divided into a maxillary/mandibular third molar absent and an existent group. The ANB angle and the sagittal dimensions of the nasal floor (ANS-PNS), maxillary basal bone (Mx), mandibular corpus (Go-Pog), and mandibular basal bone (Mn) were measured. Logistic regression analysis was used to estimate associations between third molar agenesis and these measures. The following results were obtained: (1) The frequency of the maxillary third molar agenesis significantly increased with decreasing Mx (odds ratio = 0.559, 95% confidence interval = 0.377 - 0.829). The frequency of the mandibular third molar agenesis also increased with decreasing Mx (odds ratio = 0.532, 95% confidence interval = 0.330 - 0.856). (2) There were no significant correlations between Mn and mandibular third molar agenesis. These results suggest that agenesis of third molar germs does not depend on anteroposterior dimensions of the mandible but depends on anteroposterior dimensions of the maxilla in Japanese orthodontic patients.


How and why do root apices sense light under the soil surface?
Light can penetrate several centimeters below the soil surface. Growth, development and behavior of plant roots are markedly affected by light despite their underground lifestyle. Early studies provided contrasting information on the spatial and temporal distribution of light-sensing cells in the apical region of root apex and discussed the physiological roles of plant hormones in root responses to light. Recent biological and microscopic advances have improved our understanding of the processes involved in the sensing and transduction of light signals, resulting in subsequent physiological and behavioral responses in growing root apices. Here, we review current knowledge of cellular distributions of photoreceptors and their signal transduction pathways in diverse root tissues and root apex zones. We are discussing also the roles of auxin transporters in roots exposed to light, as well as interactions of light signal perceptions with sensing of other environmental factors relevant to plant roots.


Pediatric and Parents' Attitudes Towards COVID-19 Vaccines and Intention to Vaccinate for Children.
Coronavirus disease 2019 (COVID-19) vaccination is necessary to reach herd immunity and essential for mitigating the spread of the pandemic. In May 2021, the US FDA and the EU have expanded the emergency use authorization for a COVID-19 vaccine to children aged 12 to 15. The aim of this study was to investigate parental acceptability of COVID-19 vaccination for their children, factors affecting their acceptability, and children's perceptions of COVID-19 vaccines in Republic of Korea. We conducted a questionnaire survey at two tertiary hospitals from May 25, 2021 to June 3, 2021. Subjects were parents having children under 18 years and children aged 10-18 years. Two hundred twenty-six parents and 117 children aged 10-18 years were included in the final analysis. Overall, 76.5% and 64.2% of parents intended to get vaccinated against COVID-19 and intended to have their children vaccinated, respectively. However, only 49.6% of children responded that they would get COVID-19 vaccination. In the multivariate analysis, high confidence in the safety of COVID-19 vaccines (adjusted odds ratio [AOR], 4.87; 95% confidence interval [CI], 1.32-24.12), parents' willingness to vaccinate themselves (AOR, 19.42; 95% CI, 6.85-64.00), and awareness of the need to vaccinate children against COVID-19 (AOR, 13.15; 95% CI, 4.77-41.27) were associated with positive factors intention to vaccinate their children. This study provides insight into how parents think about the COVID-19 vaccine for their children in South Korea. Our findings could be referenced in establishing a policy for childhood COVID-19 vaccination in the future.


Evaluation of Aquacel Ag for Autogenous Skin Donor Sites.
An ongoing objective of burn research is to evaluate wound dressings and develop new treatments to expedite wound healing. This was a single-center, prospective, randomized, controlled study to evaluate the effectiveness of Aquacel Ag as a dressing for autogenous skin donor sites compared with Xeroform. We hypothesized that donor sites treated with Aquacel Ag would heal faster. Patients were considered for enrollment if they required skin grafting with two donor sites >100 cm at least 2 inches apart. Dressings were observed daily starting on post-op day #2 until discharge and then weekly in the outpatient burn clinic. Assessments evaluated pain, infection, and reapplication. Photographs were taken on post-op day #2, upon "90% re-epithelialization," and at post-op day #30-45. Scar assessments and blinded photographic reviews were completed to assess cosmetic healing. Twenty-nine patients completed the study. Re-epithelialization occurred faster with Xeroform (15.2 days vs. 17.6 days). Daily pain scores were higher with Xeroform (6.72 vs. 5.68) and Aquacel Ag needed to be replaced more often (1.72 times vs. 0.10 times). Three patients developed donor site infections with Aquacel Ag. Scar scores between the donor sites were not statistically significant. The blinded photo review concluded that Xeroform had a better cosmetic outcome (24 vs. 10%). Although patients complained of more pain with Xeroform, it demonstrated shorter healing times and better cosmetic outcomes. Aquacel Ag needed to be replaced more often and represented the only three donor site infections.


[Bernardo de Cienfuegos and his contribution to botany in the 17th century].
The 17th century represented a parenthesis in Spain's scientific development at an institutional level although learning was preserved and transmitted to the incoming generations by means of individual personalities. Bernardo de Cienfuegos, a physician and botanist, wrote his works in the first half of the 17th century. These amount to seven hand-written bound volumes that are kept at the Spanish National Library and contain some 1,000 drawings of plants, most of them in colour. They actually are a monumental work of recopilation that gather a great number of original data about plants and their application, especially in the realm of medicine.


High-accuracy 3D shape measurement of translucent objects by fringe projection profilometry.
Acquiring complete and accurate 3D shape measurement results of translucent objects by fringe projection profilometry (FPP) is difficult because of the subsurface scattering effect. The phase offset introduces geometric errors, and the degraded image contrast leads to incomplete measurement results and random errors. In this research, a high-accuracy 3D shape measurement method for translucent objects based on phase-shifting FPP is proposed. The relationship between fringe period and phase error is investigated to determine the fringe periods. Random errors are suppressed by temporal noise reduction, and the robustness of multi-frequency heterodyne phase unwrapping is improved by increasing the interval of fringe periods along with temporal noise reduction. Geometric errors are compensated for by projecting multi-frequency fringe patterns to establish the relationship between fringe period and depth offset. Experimental results show that the proposed method can acquire complete measurement results and significantly reduce the overall error for measuring translucent objects.