Using a geographical information system to map the distribution of dentists in Ohio.
Studies have reported that dental care is the highest unmet health care need in the United States and have evaluated this in terms of individual determinants of access and utilization. None of these studies took into consideration the provider issues of availability and accessibility or of spatial relations. The aim of this study was to analyze issues of provider availability and accessibility in Ohio using a geographical information system, or GIS. Three Ohio databases were geocoded using GIS software. The databases included all 6,132 dentists licensed to practice in Ohio, 1,898 dentists who had billed the state Medicaid program in 1998 and safety-net clinics that provided free or low-cost care. Each practitioner was mapped at the county and ZIP code levels. Results are reported using maps at the county and ZIP code levels. The maps showed that 69.4 percent of dentists practiced in 12 metropolitan counties, 14 percent in 17 suburban counties and 16.6 percent in 59 rural counties (rural non-Appalachian counties plus Appalachian counties). In Appalachia, the dentist-to-population ratio was about one-half that of the metropolitan counties. Obvious disparities exist in the distribution of dentists in Ohio, particularly in rural and Appalachian counties. The need to increase the availability of dentists in these counties is evident. GIS is a useful tool for evaluating provider distribution and availability and planning programs to attract dentists to areas with small numbers of dentists.


A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.
The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.


Retracted: Autopsy and Histologic Findings of Patients with New Coronavirus Pneumonia: The Pathologic Associations with Hypoxemia.
This manuscript has been retracted due to the identification of undeclared duplication of content, including Figure images, from a -previous publication by some of the authors: Wang C, Xie J, Zhao L, Fei X, Zhang H, Tan Y, Nie X, Zhou L, Liu Z, Ren Y, Yuan L, Zhang Y, Zhang J, Liang L, Chen X, Liu X, Wang P, Han X, Weng X, Chen Y, Yu T, Zhang X, Cai J, Chen R, Shi ZL, Bian XW. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBioMedicine. 2020; 57: 102833. All authors are requested to declare that manuscripts submitted to this journal are original. This journal makes clear that research fraud of any kind will not be tolerated and will result in immediate retraction.


Histopathological changes in the eyes of mangabey monkeys with lepromatous leprosy.
Leprosy is the third leading cause of preventable blindness; however, little is known about the spread of infection to the eye. We have studied the eyes of three sooty managabey monkeys. Two were experimentally infected with Mycobacterium leprae; the third was not infected. In one of the infected animals there was histopathological evidence of lepromatous leprosy as evidenced by a chronic inflammatory infiltrate at the limbus, and detection of acid-fast bacilli in the corneal stroma, blood vessel walls, and corneal nerves. The latter were damaged as a result of the bacillary invasion. Electron microscopy revealed involvement and distortion of keratocytes with M. leprae and invasion of the corneal stroma by macrophages containing bacilli. Both infected animals showed focal collections of lymphocytes in the superficial stroma of the conjunctiva and in the ciliary body. This is the first report of the ocular manifestations of leprosy in any primate, including man, in which the duration of infection is known.


Effect of Modified Phospholipid Bilayers on the Electrochemical Activity of a Membrane-Spanning Conjugated Oligoelectrolyte.
The incorporation and electrochemical activity of a conjugated oligoelectrolyte (COE) in model phospholipid bilayers have been characterized using cyclic voltammetry and UV-vis absorption measurements. Several other modifiers were also incorporated into the phospholipid membranes to alter properties such as charge and alkyl chain disorder. Using potassium ferricyanide to measure charge transport, it was observed that bilayers that contained cholic acid, a negatively charged additive that also promotes alkyl chain disorder, had higher COE uptake and charge permeability than unmodified bilayers. In contrast, when the positively charged choline was incorporated, charge permeability decreased and COE uptake was similar to that of unmodified bilayers. The incorporation of cholesterol at low concentrations within the phospholipid membranes was shown to enhance the COE's effectiveness at increasing membrane charge permeability without increasing the COE concentration in the bilayer. Higher concentrations of cholesterol reduce membrane fluidity and membrane charge permeability. Collectively, these results demonstrate that changes in phospholipid membrane charge permeability upon COE incorporation depend not only on the concentration in the membrane but also on interactions with the phospholipid bilayer and other additives present in the membranes. This approach of manipulating the properties of phospholipid membranes to understand COE interactions is applicable to understanding the behavior of a wide range of molecules that impart useful properties to phospholipid membranes.


Grape skin extract mitigates tissue degeneration, genotoxicity, and oxidative status in multiple organs of rats exposed to cadmium.
The aim of this study was to investigate whether grape skin extract can mitigate the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis for the liver, genotoxicity, and oxidative status in the blood and liver were investigated in this setting. A total of 20 Wistar rats weighing 250 g, on average, and 8 weeks of age were distributed into four groups (n=5) as follows: control group (nontreated group); cadmium group (Cd); and grape skin extract groups (Cd+GS) at 175 or 350 mg/l. Histopathological analysis in liver showed that animals treated with grape skin extract showed improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as indicated by comet and micronucleus assays in animals treated with grape skin extract. Copper-zinc superoxide dismutase and cytochrome c gene expression increased in groups treated with grape skin extract in liver cells. Grape skin extract also reduced the 8-hydroxy-2'-deoxyguanosine levels in liver cells compared with the cadmium group. Taken together, our results indicate that grape skin extract can mitigate tissue degeneration, genotoxicity, and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.


SARS-CoV-2 and HIV protease inhibitors: why lopinavir/ritonavir will not work for COVID-19 infection.
Since the beginning of the outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV) 2, lopinavir/ritonavir was selected for treatment. The recent publication of Cao et al. in the New England Journal of Medicine showed that lopinavir/ritonavir treatment did not accelerate clinical improvement compared with standard of care. This raised the question of whether in retrospect we could have known this. The aim of this paper is to gather all the available evidence and to comprehensively discuss this issue.


Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision.
To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision. A retrospective review of all patients with microvascular free tissue transfer to the head and neck between August 2013 and July 2021. Otolaryngology-Head and Neck Surgery Departments at University of Alabama at Birmingham, University of Colorado, and University of California Irvine. Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA) and vasopressor use, and leech therapy were collected plus microvascular free flap outcomes. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed. A total of 843 microvascular free flaps were included. The overall rate of flap failure was 4.0% (n = 34). The overall rate of pedicle anastomosis revision (artery, vein, or both) was 5.0% (n = 42) with a failure rate of 47.6% (n = 20) after revision. Anastomotic revision significantly increased the risk of flap failure (odds ratio [OR] 52.68, 95% confidence interval [CI] [23.90, 121.1], p < .0001) especially when both the artery and vein were revised (OR 9.425, 95% CI [2.117, 52.33], p = .005). Free flap failure after the anastomotic revision was not affected by postoperative antiplatelet therapy, postoperative prophylactic anticoagulation, intraoperative heparin bolus, tPA, and therapeutic anticoagulation regardless of which vessels were revised and if a thrombus was identified. In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.


Evaluation of candidate reference genes for expression studies in Pisum sativum under different experimental conditions.
Reverse transcription quantitative real-time polymerase chain reaction is the most accurate measure of gene expression in biological systems. The data are analyzed through a process called normalization. Internal standards are essential for determining the relative gene expression in different samples. For this purpose, reference genes are selected based on their constitutive expression across samples. At present, there has not yet been any reference gene identified in any organism that is universally optimal across different tissue types or disease situations. Our goal was to test the regulation of 11 potential references for pea. These included eight commonly used and three new candidates. Twenty-six samples, including different tissues, treatments and genotypes, were addressed in this analysis. For reliable data normalization, the most suitable combination of reference genes in each experimental set was constructed with at least two out the five more stably expressed references in the whole experimental series (i.e. protein phosphatase 2A, beta-tubulin, GH720838, actin and GH720808). To validate the determined measure of gene-stability, the gene-specific variation was calculated using different normalization factors. The most non-specific variation was removed when the most stable genes were used, highlighting the importance of the adequate choice of internal controls in gene expression experiments. The set of reference genes presented here will provide useful guidelines as starting point for reference gene selection in pea studies under conditions other than those tested here.


Synthesis of low-hemolytic antimicrobial dehydropeptides based on gramicidin s.
The synthesis and biological activity of a novel cyclic beta-sheet-type antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS analogue, containing two (Z)-(beta-3-pyridyl)-alpha,beta-dehydroalanine (DeltaZ3Pal) residues at the 4 and 4' positions (2), was synthesized by solution-phase methodologies using Boc-Leu-DeltaZ3Pal azlactone. Analogue 2 exhibited high antimicrobial activity against Gram-positive bacteria and had much lower hemolytic activity than wild-type GS and the corresponding (Z)-alpha,beta-dehydrophenylalanine (DeltaZPhe) analogue (1).


Immunological mutational signature in adenosquamous cancer of pancreas: an exploratory study of potentially therapeutic targets.
Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP. We compared the mutational status of a customized gene panel, including 41 genes involved in immunity checkpoint, inflammation and control of leukocytes, B and T cells proliferation of PDAC and ASCP. Moreover, we evaluated the immunohistochemical expression of programmed death ligand 1 (PD-L1). We observed a status of 'hypermutation' of genes included in our panel in ASCP (22/41 mutated genes). Furtheremore, PD-L1 was found to be expressed in about 15% of the squamous component of ASCP tissue. Due to genetic characteristics and to PD-L1 expression in ASCP compared to PDAC tissue, we can conclude that ASCP presents a potential sensitivity to immunological therapy.


Host GRXC6 restricts Tomato yellow leaf curl virus infection by inhibiting the nuclear export of the V2 protein.
Geminiviruses cause serious symptoms and devastating losses in crop plants. With a circular, single-stranded DNA genome, geminiviruses multiply their genomic DNA in the nucleus, requiring the nuclear shuttling of viral proteins and viral genomic DNAs. Many host factors, acting as proviral or antiviral factors, play key roles in geminivirus infections. Here, we report the roles of a tomato glutaredoxin (GRX), SlGRXC6, in the infection of Tomato yellow leaf curl virus (TYLCV), a single-component geminivirus. The V2 protein of TYLCV specifically and preferentially interacts with SlGRXC6 among the 55-member tomato GRX family that are broadly involved in oxidative stress responses, plant development, and pathogen responses. We show that overexpressed SlGRXC6 increases the nuclear accumulation of V2 by inhibiting its nuclear export and, in turn, inhibits trafficking of the V1 protein and viral genomic DNA. Conversely, the silenced expression of SlGRXC6 leads to an enhanced susceptibility to TYLCV. SlGRXC6 is also involved in symptom development as we observed a positive correlation where overexpression of SlGRXC6 promotes while knockdown of SlGRXC6 expression inhibits plant growth. We further showed that SlGRXC6 works with SlNTRC80, a tomato NADPH-dependent thioredoxin reductase, to regulate plant growth. V2 didn't interact with SlNTRC80 but competed with SlNTR80 for binding to SlGRXC6, suggesting that the V2-disrupted SlGRXC6-SlNTRC80 interaction is partially responsible for the virus-caused symptoms. These results suggest that SlGRXC6 functions as a host restriction factor that inhibits the nuclear trafficking of viral components and point out a new way to control TYLCV infection by targeting the V2-SlGRXC6 interaction.


Siblings' Power and Influence in Polyadic Family Conflict During Early Childhood.
This study examined sibling behavior during polyadic family conflicts (involving three or more family members) by identifying operational conflict elements (i.e., roles, topic), power strategies, effective influence of power, and social domain argumentation. Polyadic conflict sequences (n = 210) were identified in 35/39 families with two siblings (aged 4 and 6) and their parents observed at home. The dominant conflict topic, siblings' use of power and power strategy executed in relation to social domain argumentation, revealed unique qualities of conflict in the polyadic family context; effective use of power strategies to facilitate favorable outcomes differed by sibling birth order. Our account presents a nuanced view of the intricacies of polyadic family conflict, which provides unique opportunities for children's learning and socialization by siblings and parents.


Changes in gastric mucosa that antedate gastric carcinoma.
Endoscopic biopsy specimens of the gastric mucosa from 13 patients who were found at follow-up examination to have gastric carcinoma were compared for abnormal histologic features, type of intestinal metaplasia, and presence of immunoreactive carcinoembryonic antigen (CEA), with specimens from 40 tumor-free controls. Villus-like changes and angular infolding, cytologic nuclear pleomorphism, distinct nuclear border, irregular thickness of the nuclear membrane, irregular chromatin clumping, prominent nucleoli, and distinct nucleoli were manifestations of the carcinoma group. Angular infolding, distinct nuclear border, irregular thickness of the nuclear membrane, and distinct nucleoli were also observed in the latent stage before detection of carcinoma. The individual features, however, lacked specificity. Histochemically, a IIB subtype of intestinal metaplasia, and immunoreactive CEA in the cytoplasm of foveolar epithelium appeared exclusively in the patients with carcinoma. These findings indicate that the gastric epithelium of patients with gastric carcinoma tends to be morphologically and histochemically abnormal even before the recognition of classical dysplasia. This can be described as abnormal epithelium and is believed to provide the soil on which gastric carcinoma develops.


Training for advanced laparoscopic surgery.
To evaluate the efficiency of training for advanced minimally-invasive surgery in rats. Teaching hospital, Germany. 10 surgical residents with few laparoscopic training skills had two days laparoscopic microsurgical training using rats. Increasingly difficult procedures started using a rubber model, followed by 'open' and 'closed' rat models simulating laparoscopic conditions. The surgical skills of all participants were assessed before and after the laparoscopic training course by applying 5 defined tasks in a simulation trainer. As a control group, 8 surgical residents with the same amount of minimal-invasive training were tested after a 2-day interval. All participants of the laparoscopic training programme significantly improved their surgical skills for all 5 tasks (p < 0.05). In the control group only one of the 5 tasks was significantly improved after repetition. Participants of the complete training programme consistently improved their surgical skills significantly compared with the controls before and after repetition (p < 0.05). Surgical training in minimal-invasive techniques in the rat model is effective and reproducible especially to improve laparoscopic skills such as bimanual tissue handling, knot tying and microsurgical suturing.


Platinum Resistance in Ovarian Cancer: Role of DNA Repair.
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. It is initially responsive to cisplatin and carboplatin, two DNA damaging agents used in first line therapy. However, almost invariably, patients relapse with a tumor resistant to subsequent treatment with platinum containing drugs. Several mechanisms associated with the development of acquired drug resistance have been reported. Here we focused our attention on DNA repair mechanisms, which are fundamental for recognition and removal of platinum adducts and hence for the ability of these drugs to exert their activity. We analyzed the major DNA repair pathways potentially involved in drug resistance, detailing gene mutation, duplication or deletion as well as polymorphisms as potential biomarkers for drug resistance development. We dissected potential ways to overcome DNA repair-associated drug resistance thanks to the development of new combinations and/or drugs directly targeting DNA repair proteins or taking advantage of the vulnerability arising from DNA repair defects in EOCs.


Isotopic evidence in tree rings for historical changes in atmospheric sulfur sources.
Little is understood about the usefulness of sulfur isotopic ratios (sigma 34S) in tree rings because the sulfur content in rings is generally insufficient for analysis using conventional methods. We present sigma 34S values of the water-soluble and the organically bound sulfur fractions in rings of coniferous trees grown in Japan, analyzed using a large-volume oxygen bomb. Comparing the sigma 34S values of the organically bound fraction in tree rings with past atmospheric sulfur concentrations and with those of their sources, we find clear evidence that the sigma 34S values of the organically bound fraction in the rings are dependent upon the values of the atmospheric sulfur sources. The evidence suggests that the sigma 34S values in tree rings are a useful chronological proxy for evaluating possible causes of past atmospheric sulfur pollution.


UroVysion™ fluorescence in situ hybridization (FISH) possibly has a high positive rate in carcinoma of non-urothelial lineages.
Background: Positive UroVysion™ fluorescence in situ hybridization (FISH) is generally considered as urothelial carcinoma (UC). We clarify if UroVysion™ FISH can be positive in carcinoma of non-urothelial lineages (CNUL), and verify the consistency of urine FISH and histological FISH in CNUL. Methods: All CNUL subjects detected by urine FISH assay due to haematuria from Tongji Hospital were screened. Meanwhile, 2 glandular cystitis and 2 urothelial carcinoma were served as negative or positive control. Paraffin-embedded tissue sections of all subjects were sent to the pathology department for histological FISH detection. Results: A total of 27 patients were included in this study, including 9 with adenocarcinomas, 11 with squamous cell carcinomas, and 7 with other tumour types. The overall positive rate in urine FISH was 64.00% (16/25) in patients with CNUL, 77.78% (7/9) in those with adenocarcinoma and 54.55% (6/11) in those with squamous carcinoma. There was a significant difference in the GLP p16 gene deletion rate between UC and CNUL (100% vs. 8.00%, p = 0.017). Histological FISH results showed that the histological results of 19 patients were consistent with their urine FISH results, and only one patient with stage Ⅲa urachal carcinoma had inconsistent histological FISH results (positive) and urine FISH (negative) results. Conclusion: We demonstrated for the first time the application value of FISH in CNUL on urine samples. Positive urine FISH tests indicate not only UC, but also CNUL. UroVysion™ FISH possibly has a high positive rate in CNUL. CNUL and UC have different genetic changes shown by FISH.


False positive Meckel's scan caused by carcinoid tumors of the small bowel.
A case of gastrointestinal bleeding caused by carcinoid tumor of the small bowel detected by a positive Meckel's scan is presented. This test may prove useful when conventional work-ups fail to localize a bleeding site.


Evidence of a paucity of genes that interact with the mitochondrion on the X in mammals.
Mitochondria are essential organelles whose replication, development, and physiology are dependent upon coordinated gene interactions with both the mitochondrial and the nuclear genomes. The evolution of coadapted (CA) nuclear-mitochondrial gene combinations would be facilitated if such nuclear genes were located on the X-chromosome instead of on the autosomes because of the increased probability of cotransmission. Here, we test the prediction of the CA hypothesis by investigating the chromosomal distribution of nuclear genes that interact with mitochondria. Using the online genome database BIOMART, we compared the density of genes that have a mitochondrion cellular component annotation across chromosomes in 16 vertebrates. We find a strong and highly significant genomic pattern against the CA hypothesis: nuclear genes interacting with the mitochondrion are significantly underrepresented on the X-chromosome in mammals but not in birds. We interpret our findings in terms of sexual conflict as a mechanism that may generate the observed pattern. Our finding extends single-gene theory for the evolution of sexually antagonistic genes to nuclear-mitochondrial gene combinations.


Characteristics of Patients Who Achieve Serum Phosphorus Control on Sucroferric Oxyhydroxide or Sevelamer Carbonate: A post hoc Analysis of a Phase 3 Study.
Control of hyperphosphatemia in patients on dialysis remains a major challenge. This study evaluated predictors of serum phosphorus (sP) control among dialysis patients treated with noncalcium, oral phosphate binder therapy in a phase 3 clinical trial. Post hoc analyses were performed using data for patients with hyperphosphatemia who received 52 weeks of treatment with sucroferric oxyhydroxide (SFOH) or sevelamer carbonate (sevelamer). Patients were categorized into those who achieved sP control (n = 302; defined as sP ≤ 5.5 mg/dL at week 52), and those with uncontrolled sP (n = 195; sP >5.5 mg/dL at week 52). Because SFOH and sevelamer have previously demonstrated similar effects on chronic kidney disease-mineral-bone disorder parameters in this study, the treatment groups were pooled. Average age at baseline was higher among sP-controlled versus sP-uncontrolled patients (56.9 vs. 53.4 years; p = 0.005). Baseline sP levels were significantly lower among sP-controlled versus sP-uncontrolled patients (7.30 vs. 7.85 mg/dL; p < 0.001), and sP reductions from baseline were significantly greater in the sP-controlled group (-2.89 vs. -0.99 mg/dL at week 52; p < 0.001). Logistic regression analysis identified higher baseline sP levels (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.765-0.960), no concomitant active vitamin D therapy use (OR = 0.51, 95% CI: 0.328-0.804), and higher body mass index at baseline (OR = 0.96, 95% CI: 0.937-0.992) as significant predictors of uncontrolled sP. This analysis indicates that sP control may be more challenging in younger patients with high sP levels. Closer monitoring and management of serum phosphorus levels may be required in this population.


Ultrasmall Ru2P nanoparticles on graphene: a highly efficient hydrogen evolution reaction electrocatalyst in both acidic and alkaline media.
Ultrasmall ruthenium phosphide nanoparticles grown on reduced graphene oxide nanosheets (Ru2P/RGO-20) are reported as a highly efficient hydrogen evolution reaction (HER) catalyst. It achieves a current density of -10 mA cm-2 at extremely low overpotentials of -22 and -13 mV under acidic and alkaline conditions, respectively, superior to those of commercial Pt/C.


Diagnosis and management of supernumerary teeth.
Supernumerary teeth can present in various forms and in any region of the mandible or maxilla, but have a predisposition for the anterior maxilla. They can cause a variety of complications in the developing dentition. This article reviews the epidemiology, clinical features, diagnosis and options for the management of supernumerary teeth. Early diagnosis and appropriate management can minimize the potential complications caused by supernumerary teeth. Dental practitioners should be aware of their clinical signs and the treatment options.


X-ray spectral measurements and collisional radiative modeling of Ni- to Kr-like Au ions in electron beam ion trap plasmas.
The line emission of n=7-->3, 6-->3, 5-->3, and 4-->3 transitions in Ni- to Kr-like gold ions produced in the Livermore electron beam ion traps EBIT-I and EBIT-II has been recorded with an x-ray crystal spectrometer and a photometrically calibrated microcalorimeter. The plasmas had either monoenergetic electron beams with E(beam)=2.66, 3.53, or 4.54 keV or an experimentally simulated thermal electron distributions with T(e)=2.5 keV. The electron densities were approximately 10(12)cm(-3). The measured spectra have been compared to atomic structure calculations and synthetic spectra provided by the Hebrew University Lawrence Livermore Atomic Code atomic data package. Line identifications and accurate photon energy measurements have been made for many collisionally excited transitions. Approximately 140 lines have been identified in nine charge states. Agreement within 20-30 % exists between the measured and modeled line intensities for most lines excited by the monoenergetic electron beam plasmas, although some larger discrepancies can be found for some weaker features.


Allergy to natural rubber latex: a growing problem.
Immediate, IgE-mediated allergy to natural rubber latex has recently been found to be responsible for contact and generalized urticaria, protein contact dermatitis, rhinitis, asthma and even fatal anaphylactic reactions. The proteins present in latex from the rubber tree (Hevea brasiliensis) can still persist in rubber end-products where they are capable of sensitizing exposed users. Atopic people and those with hand eczema are prone to become sensitized by natural rubber latex, which often causes occupational problems in connection with the use of protective gloves. But people blowing up balloons and those using condoms are also at risk if their symptoms are misinterpreted. Severe adverse reactions caused by rubber products in medicare cannot be prevented if the diagnosis has not been made before operations and medical examinations. So the most important task today is to develop reliable and safe methods for diagnosing natural rubber latex allergy and to manufacture rubber products with fewer allergens.


Spectral analysis of EEG in normal and sulfite oxidase deficient rats under sulfite administration.
This article investigated the possible neurotoxic effect of sulfite in normal and sulfite oxidase (SOX) deficients rats by evaluating EEG spectral analysis. Rats were divided into four groups: control (C), sulfite treated (25 mg/kg) (ST), SOX deficient (SD), and sulfite treated SOX deficient (STSD) groups. The qEEG spectral analyses of two spectral parameters including power and relative power were performed. The mean power of SD group was found to be increased compared to the all other groups and returned to control levels after sulfite administration. The power of the four frequency bands (delta, theta, alpha, beta) of the SD group corresponds to the mean power. EEG relative power increased in the delta band with concomitant decreases in power measured in the alpha frequency range. It was concluded that exogenous administration of sulfite affected the brain electrical activity in SOX deficiency, and improved neuroprotection.


Arachnoid isolation sign: A predictive imaging feature of spinal meningioma on CT-myelogram.
Numerous studies have demonstrated the imaging features to differentiate spinal meningioma and schwannoma. However, diagnosis can be controversial among clinicians. The purpose of our study was to evaluate the diagnostic value of a novel imaging finding of meningioma on CT-myelogram (CTM). Imaging findings of patients who underwent surgeries for spinal cord tumors between April 2005 to May 2015 were retrospectively reviewed. Our inclusion criteria were as follows: 1) intradural extramedullary tumor, 2) both magnetic resonance imaging (MRI) and CTM were available. The exclusion criterion was a tumor that showed invasion to extradural space. Thirty spinal meningiomas and schwannomas were identified (eight meningiomas and 22 schwannomas). Among these, two meningiomas showed a characteristic imaging phenomenon on CTM: they were diagnosed as intradural tumors on MR imaging while on CTM, they were isolated by the contrast agent in subarachnoidal space from the intact spinal cord. We named this imaging feature, the arachnoid isolation sign (AIS). None of the schwannomas showed this imaging feature. We identified a unique imaging feature of spinal meningioma on CTM. The sensitivity and specificity were 25% and 100%, respectively. In the current case, its diagnostic value was the same as the calcification on CT. Although the number is still small, the AIS may be useful to discern a spinal meningioma from schwannoma.


[Methodological possibilities for in vitro evaluation of the antibiotic sensitivity of bacterial plaque from periodontal pockets].
Two different methods for making the subuletic bacterial antibiogram were compared, namely, the inhibition halo technique and that of percentage reduction. The first, of the more classical nature, is based on the introduction of the antibiotic inside a small cavity made in the culture medium, which leads to the formation of circular haloes around the cavity itself. The magnitude of the hales is all the greater, the more effective the antibiotic. The percentage-reduction technique calculates the reduction, expressed as a percentage, of the total number of colonies grown in the cultural medium containing the antibiotic, with respect to the number of colonies grown on a control culture-plate without antibiotic. Both techniques gave unambiguous results in 92.8% of the cases, both showing satisfactory validity; however, the percentage reduction technique proved to be more complex, to require fuller investigation and to be more expensive than the other. In fact, to make the antibiogram of a bacterial plaque concerning the seven antibiotics tested, 24 plates of agar-culture were necessary with the "r" method, whereas, with that of "inhibition haloes" only two sufficed. In addition, in the case of plaques with scarce microbial density or in the presence of highly invasive germs, by using the "inhibition haloes" method, it is always possible to have some information, which is impossible with the other method.


Factors associated with autopsy rates in a 6-year sample of Danish suicides in the Capital area of Copenhagen.
On average, two suicides occur in Denmark every day. In order to prevent suicides, it is important to understand their nature. The forensic autopsy plays an important role by providing detailed knowledge of the cause and manner of death. Unfortunately, the autopsy rate for suicides in Denmark is very low. The aim of this study was to elucidate the factors that may affect the decision to perform a forensic autopsy and thereby affect the autopsy rate of suicidal deaths in the Capital area of Copenhagen. Data from 6211 death certificates from the Capital area of Copenhagen, Denmark, over a study period of six years, were investigated. For deaths classified as suicide, the presence of the following factors were registered: gender, age, date of birth, date of death, marital status, nationality, place of death, cause of death, psychiatric condition, former admissions at a psychiatric ward, former attempts of suicide, presence of suicide note, history of substance abuse (alcohol, narcotics or both), and presence of self-inflicted scars. These factors were cross-tabulated with whether a referral to a forensic autopsy was made. Significant association was calculated by using Chi2 and Fisher's exact test. We found a total of 381 cases of suicide. The forensic autopsy rate was 21.3%. The following factors were associated with a significantly lower forensic autopsy rate: age above 50, history of psychiatric illness, the presence of a suicide letter, and cause of death registered as hanging/strangulation/suffocation, drowning/submersion, self-harm with sharp object, and jumping from height. Only the presence of a suicide letter remained significant after the Bonferroni correction for multiple testing. History of substance abuse and cause of death registered as intentional exposure to smoke, fire and flames were associated with a significantly higher forensic autopsy rate. A forensic autopsy can give more precise information on suicide methods, the impact of fatal lesions and comorbidity. Our study results showed that violent methods of suicidal death and psychiatric comorbidity led to a lower forensic autopsy rate. A higher autopsy rate would enable more thorough study and investigation of suicides, which would benefit the next-of-kin, general preventive procedures, and treatment of patients at risk of suicide.


Advanced wasting in peritoneal dialysis patients.
To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero. Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0.73 is the water fraction of FFM at normal hydration. Wasting from loss of BF has adverse survival outcomes in PD. Advanced wasting was defined as zero BF when V/0.73 is equal to or exceeds W. This study, which analyzed 439 PD patients at their first clearance study, used the Watson formulas estimating V to identify patients with VWatson/0.73 ≥ W and compared their nutritional indices with those of PD patients with VWatson/0.73 < W. The study identified at the first clearance study two male patients with VWatson/0.73 ≥ W among 439 patients on PD. Compared to 260 other male patients on PD, the two subjects with advanced wasting had exceptionally low body mass index and serum albumin concentration. The first of the two subjects also had very low values for serum creatinine concentration and total (in urine and spent peritoneal dialysate) creatinine excretion rate while the second subject had an elevated serum creatinine concentration and high creatinine excretion rate due, most probably, to non-compliance with the PD prescription. Advanced wasting (zero BF) in PD patients, identified by the anthropometric formulas that estimate V, while rare, is associated with indices of poor somatic and visceral nutrition.


Effect of macrolide antibiotics on neutrophil function in human peripheral blood.
Since "small-dose and long-term" administration of erythromycin (EM) was shown to be efficacious in the treatment of chronic respiratory disease, the modulation of host defense responses by EM has attracted much attention. Although there is considerable controversy, it was recently demonstrated that EM activity reduces neutrophil function. In this study, we investigated the in vitro effects of the macrolides erythromycin (EM), a 14-membered ring, azithromycin (AZM), a 15-membered ring and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function. The DCFH-DA method and cytochrome C method were used for assay of active oxygen generation and the Boyden-chamber method was used for assay of chemotaxis. EM and AZM, both of which have been shown to be clinically effective in the treatment of Diffuse panbronchiolitis (DPB), significantly suppressed active oxygen generation and chemotaxis of neutrophils at low concentrations equivalent to therapeutic doses (0.5 approximately 1.0 microgram/ml, p < 0.05), whereas the clinically ineffective RKM did not. The in vitro inhibitory effects of EM and AZM on active oxygen generation and chemotaxis of neutrophils demonstrated in the present study may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in the treatment of DPB patients.


The Long-Term Study of Urinary Biomarkers of Renal Injury in Spontaneously Hypertensive Rats.
The age-related increase in blood pressure in spontaneously hypertensive rats (SHRs) is associated to cardiac hypertrophy, heart failure, and renal injury. Here, we investigated for the first time the urinary enzymatic activities of glutamil aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), and Klotho urinary levels, proteins that are strongly expressed in the kidney, as early biomarkers of renal injury in SHRs. Male SHR and Wistar Kyoto (WKY) rats were studied from 2 to 8 months old. Systolic blood pressure (SBP), the heart rate (HR), metabolic variables, and urinary markers were measured monthly. At the end of the study, a histopathological evaluation of the kidney was performed. Kidneys of SHR did not develop signs of relevant histopathological changes, but showed increased glomerular area and cellularity. Plasma creatinine was decreased, and creatinine clearance was augmented in SHR at the end of the study. Urinary excretion of Klotho was higher in SHR at 5 and 8 months old, whereas plasma Klotho levels were similar to WKY. GluAp, AlaAp, and DPP4 urinary activities were increased in SHR throughout the time-course study. A positive correlation between glomerular area and cellularity with creatinine clearance was observed. Urinary GluAp, AlaAp, DPP4, and Klotho showed positive correlations with SBP. GluAp, AlaAp, DPP4, and Klotho in the urine are useful tools for the evaluation of renal damage at early stages, before the whole histopathological and biochemical manifestations of renal disease are established. Moreover, these observations may represent a novel and noninvasive diagnostic approach to assess the evolution of kidney function in hypertension and other chronic diseases.


Analysis of chromosomes from human peripheral lymphocytes by flow cytometry.
A method of preparation and flow cytometric analysis of chromosomes from human peripheral lymphocytes is described. The procedure allows a resolution coefficient of variation better than 3% using propidium iodide staining and a commercially available flow cytometer.


A Systematic Review of Definitions for Dysphagia and Dysphonia in Patients Treated Surgically for Degenerative Cervical Myelopathy.
Systematic review. Surgical decompression for degenerative cervical myelopathy (DCM) is associated with perioperative complications, including difficulty or discomfort with swallowing (dysphagia) as well as changes in sound production (dysphonia). This systematic review aims to (1) outline how dysphagia and dysphonia are defined in the literature and (2) assess the quality of definitions using a novel 4-point rating system. An electronic database search was conducted for studies that reported on dysphagia, dysphonia or other related complications of DCM surgery. Data extracted included study design, surgical details, as well as definitions and rates of surgical complications. A 4-point rating scale was developed to assess the quality of definitions for each complication. Our search yielded 2,673 unique citations, 11 of which met eligibility criteria and were summarized in this review. Defined complications included odynophagia (n = 1), dysphagia (n = 11), dysphonia (n = 2), perioperative swelling complications (n = 2), and soft tissue swelling (n = 3). Rates of dysphagia varied substantially (0.0%-50.0%) depending on whether this complication was patient-reported (4.4%); patient-reported using a modified Swallowing Quality of Life questionnaire (43.1%) or the Bazaz criteria (8.8%-50.0%); or diagnosed using an extensive protocol consisting of clinical assessment, a bedside swallowing test, evaluation by a speech and language pathologist and a modified barium swallowing test/fiberoptic endoscopy (42.9%). The reported incidences of dysphonia also ranged significantly from 0.6% to 38.0%. There is substantial variability in reported rates of dysphagia and dysphonia due to differences in data collection methods, diagnostic strategies, and definitions. Consolidation of nomenclature will improve evaluation of the overall safety of surgery.


Conformational changes and loss of opsonic function in frozen or heat-treated plasma fibronectin.
Using human peripheral blood monocytes to assay opsonic protein activity, we have examined the efficiency of various procedures for isolating fibronectin from plasma for experimental or therapeutic use. In addition, we have assessed the protein's opsonic activity after cold storage, and after heat treatment to inactivate hepatitis virus. The purification procedures recovered only 30% of available plasma fibronectin whilst cold storage and heat treatment of the purified protein removed all of its remaining opsonic activity. This was associated with no alteration in overall molecular weight or in subunit size but was accompanied by changes in ultraviolet spectrum, suggesting a conformational change in the protein structure. Initial experiments to protect the purified protein against these changes were unsuccessful and unless further attempts are more encouraging, fresh-frozen plasma may be the only current economic source of opsonically active fibronectin. Since this would waste other valuable proteins required for other purposes, the widespread use of plasma fibronectin outside of clinical trials may be unjustified at this present time.


Short Self-Assembling Peptides Are Able to Bind to Copper and Activate Oxygen.
We have shown that de novo designed peptides self-assemble in the presence of copper to create supramolecular assemblies capable of carrying out the oxidation of dimethoxyphenol in the presence of dioxygen. Formation of the supramolecular assembly, which is akin to a protein fold, is critical for productive catalysis since peptides possessing the same functional groups but lacking the ability to self-assemble do not catalyze substrate oxidation. The ease with which we have discovered robust and productive oxygen activation catalysts suggests that these prion-like assemblies might have served as intermediates in the evolution of enzymatic function and opens the path for the development of new catalyst nanomaterials.


Synthesis of C14,15-dihydro-C22,25-epi north unit of cephalostatin 1 via "red-ox" modifications of hecogenin acetate.
The C14,15-dihydro-C22,25-epi north unit of cephalostatin 1 has been synthesized in 11 operations from commercially available hecogenin acetate via multiple reductions and oxidations. The key transformations include (i) Cr(VI)-catalyzed E-ring opening, (ii) C17 hydroxylation, and (iii) a base-triggered cyclization cascade.


Argininosuccinate synthase 1 is an intrinsic Akt repressor transactivated by p53.
The transcription factor p53 is at the core of a built-in tumor suppression system that responds to varying degrees of stress input and is deregulated in most human cancers. Befitting its role in maintaining cellular fitness and fidelity, p53 regulates an appropriate set of target genes in response to cellular stresses. However, a comprehensive understanding of this scheme has not been accomplished. We show that argininosuccinate synthase 1 (ASS1), a citrulline-aspartate ligase in de novo arginine synthesis pathway, was directly transactivated by p53 in response to genotoxic stress, resulting in the rearrangement of arginine metabolism. Furthermore, we found that x-ray irradiation promoted the systemic induction of Ass1 and concomitantly increased plasma arginine levels in p53+/+ mice but not in p53-/- mice. Notably, Ass1+/- mice exhibited hypersensitivity to whole-body irradiation owing to increased apoptosis in the small intestinal crypts. Analyses of ASS1-deficient cells generated using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) system revealed that ASS1 plays a pivotal role in limiting Akt phosphorylation. In addition, aberrant activation of Akt resulting from ASS1 loss disrupted Akt-mediated cell survival signaling activity under genotoxic stress. Building on these results, we demonstrated that p53 induced an intrinsic Akt repressor, ASS1, and the perturbation of ASS1 expression rendered cells susceptible to genotoxic stress. Our findings uncover a new function of p53 in the regulation of Akt signaling and reveal how p53, ASS1, and Akt are interrelated to each other.


Money talks, money kills -- the economics of transplantation in Japan and China.
Japan and China have long resisted the Western trend of organ transplantation from brain-dead patients, based on a 'Confucian' respect for integrity of ancestors' bodies. While their general publics continue to harbor grave doubts about such practices, their medical and political elites are hastening towards the road of organ-harvesting and organ-marketing, largely for economic reasons. This report illustrates the ways that economics is motivating brain-death legislation in Japan and criminal executions in China.


Intra-parotid dermoid cyst: excision through a face lift incision.
Intra-parotid dermoid cysts are extremely rare. Clinically, they present like any other parotid lump and pre-operative diagnosis is rarely possible. A 62 years old Caucasian man presented with a painless lump in his right parotid region. The Magnetic Resonance Imaging (MRI) scan revealed a 3 x 3 cm mass in the parotid tail. Cytological examination was unhelpful. The patient underwent successful excision of the cyst through a small face lift incision. No drain was inserted and the patient was discharged home the same day. The patient made an uneventful recovery and was highly satisfied with the aesthetic outcome. The definite histopathological diagnosis was an intra-parotid dermoid cyst.


Reproducibility of intravenous intermittent triggered myocardial contrast echocardiography in healthy subjects.
Few data have been published on the reproducibility of baseline subtracted peak intensity obtained from intravenous intermittent triggered myocardial contrast echocardiography. We investigated the reproducibility of the peak intensity measured from intravenous intermittent triggered myocardial contrast echocardiography in 10 young healthy males. The contrast echocardiography was obtained using the second harmonic mode with an intravenous bolus injection of Levovist (first study). The same myocardial contrast echocardiography was repeated after the first study (second study). The myocardial opacification and peak intensity in the 12 segments of the apical 4 and 2 chamber views were assessed visually and quantitatively. The differences in the peak intensity between the initial and repeated measurements in the first study (intraobserver reproducibility) and between the initial measurements in the first and second studies (interinjection reproducibility) were assessed using the Bland and Altman method. The degree of opacification was good or intermediate in 207/228 (91%) of the segments. The agreement of myocardial opacification between the first and second studies was 87/114 (76%). However, significantly higher peak intensity was obtained in apical septal (8200 +/- 6300 au2) and mid septal (8500 +/- 6000 au2) segments in the 4 chamber view and in the mid inferior (12400 +/- 9300 au2) and apical inferior (10700 +/- 6300 au2) segments in the 2 chamber view compared with other segments. The mean differences of the peak intensities according to the Bland and Altman analysis was -1600 +/- 5000 au2 in the intraobserver reproducibility study, and -1100 +/- 5300 au2 in the interinjection reproducibility study. Thus, the measurement error was determined to range from 8400 au2 to 9500 au2 in both studies. We conclude that the peak intensity obtained from intravenous intermittent triggered myocardial contrast echocardiography using Levovist varies significantly among segments in the left ventricular myocardium. Large intraobserver and interinjection variability exists in the measurement of peak intensity, suggesting that the reproducibility of this technique is limited for quantitative assessment of myocardial perfusion.


Healthy eating, exercise, and weight: impressions of sexual minority women.
Obesity is a risk factor for multiple disease outcomes, including cancer and cardiovascular disease. A healthy diet and physically active lifestyle can prevent obesity. Sexual orientation is an important demographic factor that has been suggested to affect engagement in health-related behaviors, and interventions developed for the general population of women are likely to be less effective in assisting sexual minority women to make healthy choices. We conducted seven focus groups with sexual minority women (i.e., lesbians and bisexual women) to explore issues, including barriers and motivations, regarding healthy eating, physical activity, and weight in this population. The participants reported a wide range of levels of engagement in health-related behaviors. While nearly all of the participants reported some awareness of the importance of good dietary choices, the majority reported some confusion about what constitutes a healthy diet. In contrast, the majority of participants seemed clearly aware that regular exercise was important for good health. These data can guide the design of effective intervention strategies to improve health behaviors in sexual minority women.


MODEL-BASED FOOD VOLUME ESTIMATION USING 3D POSE.
We are developing a dietary assessment system to automatically identify and quantify foods and beverages consumed by analyzing meal images captured with a mobile device. After food items are segmented and identified, accurately estimating the volume of the food in the image is important for determining the nutrient content of the food. In this paper, we proposed a novel food portion size estimation method for rigid food items using a single image. First, we create a 3D graphical model during the training step using 3D reconstruction from multiple views. Then, for each food image, we determine the translation and elevation parameters of each of the food items, which are relative to the camera coordinate through camera calibration. Using these geometric parameters we project the pre-built 3D model of each food item back to the image plane. Subsequently, the remaining degrees-of-freedom (DOF) for the final pose is estimated by image similarity measure. The experimental results of our volume estimation method for four food categories validate the accuracy and reliability of our model-based approach.


Traumatic subconjunctival lens dislocation.
Traumatic crystallin lens dislocation is a common complication following open globe injuries. Wound repair, lensectomy, and prophylactic antibiotic administration are essentials in the management.


Functional electrical stimulation in paraplegic spastic patients.
We are reporting on the clinical and physiological effects of 8 months of functional electrical stimulation (FES) of the quadriceps femoris muscle on 10 paraplegic patients. Each patient had muscle biopsies, computed tomography (CT) muscle diameter measurements, and knee extension strength testing both before and after 8 months of FES training. Skin perfusion was documented through infrared telethermography and xenon clearance; muscle perfusion was recorded through thallium scintigraphy. After 8 months of FES training, the baseline skin perfusion showed an 86% increase; muscle perfusion was augmented by 87%. Muscle fiber diameters showed an average increase of 59% after 8 months of FES training. Muscles in patients with spastic paresis showed an increase in aerobic and anaerobic muscle enzymes up to the normal range of healthy humans. The increment in muscle area, as visible on CT scans of the quadriceps femoris muscle, was 30%. Using FES, we were able to improve metabolism and to induce positive trophic changes in our patients' lower extremities. In spastic paraplegics, rising and walking achieved through FES are much better training than FES ergometer training. Larger muscle masses are activated, and the heart rate is increased; therefore, the impact on cardiovascular fitness and metabolism is much greater. This effectively addresses and prevents the problems that result from inactivity in paraplegic patients.


Pedicled deep inferior epigastric perforator flap for total phallic reconstruction.
Total phallic reconstruction remains a great challenge in reconstructive surgery. The search for a suitable donor site is never ending. Based on the experiences in using free deep inferior epigastric perforator flap for breast reconstruction, the authors describe a new usage of the deep inferior epigastric perforator flap for phallic reconstruction. In this procedure, the neourethra is centrally located. The rigidity is provided with the 12th rib. The donor site can directly be closed. Over the past 4 years, this surgical procedure has been used successfully for total phallic reconstruction in 2 patients. Four years of follow-up has revealed that an aesthetically acceptable functional neopenis was achieved. The scar of the donor site is inconspicuous and is easily concealed by underwear. Moreover, this new procedure is a nonmicrosurgical technique. Although more clinical experience is needed, this flap can be chosen as an alternative option in phallic reconstruction.


"Floating" MMPI profiles revisited.
Attempted to replicate and update the characteristics of a sample of hospitalized psychiatric patients who produced "floating" MMPI profiles (N = 69). While the demographic data were somewhat different, the historical information, types of psychopathology and symptoms observed, and response to treatment were markedly similar. If diagnosed using DSM-III, approximately 30% of the patients would be classified as borderline character disorder, while another 20% would be classified as major depressive disorder.


Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation.
Mechanisms influencing the development of olfactory bulb glomeruli are poorly understood. While odor receptors (ORs) play an important role in olfactory sensory neuron (OSN) axon targeting/coalescence (Mombaerts et al., 1996; Wang et al., 1998; Feinstein and Mombaerts, 2004), recent work showed that G protein activation alone is sufficient to induce OSN axon coalescence (Imai et al., 2006; Chesler et al., 2007), suggesting an activity-dependent mechanism in glomerular development. Consistent with these data, OSN axon projections and convergence are perturbed in mice deficient for adenylyl cyclase III, which is downstream from the OR and catalyzes the conversion of ATP to cAMP. However, in cyclic nucleotide-gated (CNG) channel knock-out mice OSN axons are only transiently perturbed (Lin et al., 2000), suggesting that the CNG channel may not be the sole target of cAMP. This prompted us to investigate an alternative channel, the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN), as a potential developmental target of cAMP in OSNs. Here, we demonstrate that HCN channels are developmentally precocious in OSNs and therefore are plausible candidates for affecting OSN axon development. Inhibition of HCN channels in dissociated OSNs significantly reduced neurite outgrowth. Moreover, in HCN1 knock-out mice the formation of glomeruli was delayed in parallel with perturbations of axon organization in the olfactory nerve. These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels.


The spiritual dimension of parenting a child with a life-limiting or life-threatening condition: A mixed-methods systematic review.
Spirituality refers to the dynamic dimension of human life that relates to the way that persons experience meaning, purpose, and transcendence. The complex task of parenting a child with a life-limiting condition may raise existential questions, which are easily overlooked by healthcare professionals. We explored how the spiritual dimension becomes manifest in parents of children in pediatric palliative care. A mixed-methods systematic review was conducted, registered in Prospero (2021 CRD42021285318). PubMed, CINAHL, Embase, PsycInfo, and Cochrane were searched for articles published between January 1, 2015 and January 1, 2023. We included original empirical studies that reported on spirituality of parents of seriously ill children, from parents' perspectives. Sixty-three studies were included: 22 North-American, 19 Asian, 13 European, 9 other. Studies varied in defining spirituality. We identified five different aspects of spirituality: religion, hope, parental identity, personal development, and feeling connected with others. All aspects could function as source of spirituality or cause of spiritual concern. Sources of spirituality helped parents to give meaning to their experiences and made them feel supported. However, parents also reported struggling with spiritual concerns. Several parents highlighted their need for professional support. Although studies vary in defining spirituality, reports on spirituality focus on how parents connect to their faith, others, and themselves as parents. Healthcare professionals can support parents by paying attention to the spiritual process parents are going through. More research is needed into how healthcare professionals can support parents of seriously ill children in this process.


Puerarin Inhibits Ferroptosis and Inflammation of Lung Injury Caused by Sepsis in LPS Induced Lung Epithelial Cells.
Background: Ferroptosis is a new type of programmed cell death, which plays an important role in lung injury caused by sepsis. Studies have reported that Puerarin (Pue) can treat lung injury caused by sepsis in children, but whether it plays a role by regulating iron death has not been reported. Methods: LPS induced human alveolar epithelial cell A549 to form a model of lung injury caused by sepsis. MTT detected the effect of Pue on A549 cell viability and the effect of Pue on LPS-induced A549 cell viability. The effects of Pue on LPS-induced inflammatory cytokines TNF-α, IL-8, IL-1β in A549 cells were determined by ELISA assay. The expression level of MDA was detected by TBARS colorimetric quantitative detection kit. GSH kit was used to detect the expression of GSH in cells. The iron kit detected the total iron level and the expression level of ferric divalent ions in the cells. DCFH-DA fluorescent probe was used to detect ROS levels. Western blot was used to detect the expression of ferroptosis-related proteins in cells. Results: Pue alleviated LPS-induced injury and inflammatory response in A549 cells, and Pue reduced the expression of ROS, MDA and GSH in LPS-induced A549 cells. In addition, Pue reduced total iron levels and ferrous ion levels in LPS-induced A549 cells, and decreased the expression of iron ferroptosis-related proteins. Conclusion: Puerarin inhibited ferroptosis and inflammation of lung injury caused by sepsis in children in LPS induced lung epithelial cells.


The role of a language scale for infant and preschool assessment.
The PLS-4 (Preschool Language Scale, 4th edition) is a psychometrically sound instrument constructed to assess language skills in children from birth to 6 years 11 months. It is a useful diagnostic and research tool that can be used to identify current comprehension and expressive language skills and can measure changes in language skills over time. The test is individually administered and includes tasks that assess skills in the areas of preverbal behaviors, as well as linguistic skills in the areas of semantics, morphology, syntax, integrative language skills, and preliteracy skills. Extensive reliability and validity evidence are presented. The test has been used extensively in research examining language development of young children from different home environments, children with identified medical conditions, and children participating in a variety of habilitation and intervention programs. Both the previous edition (PLS-3) and the new PLS-4 English and Spanish editions are used extensively in clinical, medical, and research settings to examine developmental language patterns of infants, toddlers, and preschoolers.


Gal-1 silenced trophoblast tumor cells (BeWo) show decreased syncytium formation and different miRNA production compared to non-target silenced BeWo cells.
Galectin-1 (gal-1), a member of the mammalian β-galactoside-binding proteins, exerts biological effects by recognition of glycan ligands, including those involved in cell adhesion and growth regulation. In previous studies, we demonstrated that gal-1 induces cell differentiation processes on the membrane of choriocarcinoma cells BeWo, including the receptor tyrosine kinases (RTKs) REarranged during Transfection (RET), Janus Kinase 2 (JAK2) and Vascular endothelial growth factor receptor 3 (VEGFR3). Furthermore, Mitogen-Activated Protein Kinases (MAPK) and serine/threonine kinases were phosphorylated by gal-1. In addition, gal-1 in trophoblast cells in vitro induced syncytium formation especially after concentration dependent stimulation of the cells with this galectin. This is in contrast to MAPK-inhibitor U0126 that reduced syncytium formation of BeWo cells. The aim of this study was to analyze the syncytium formation abilities of BeWo cells that were gal-1 silenced. We found a significantly reduced syncytium formation rate in gal-1 silenced BeWo cells. In addition, these cells show a different miRNA expression profile. In summary, we found that gal-1 is a major trigger for fusion processes in BeWo cells. This function is accompanied by different regulation of miRNA synthesis in the BeWo cell culture model.


Pathogenesis of HCV-associated HCC: Dual-pass carcinogenesis through activation of oxidative stress and intracellular signaling.
Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma (HCC). It remains controversial, however, in the pathogenesis of HCC associated with HCV, whether the virus plays a direct role or merely an indirect one. The studies using transgenic mouse models by us and others, in which the core protein of HCV has oncogenic potential, indicate that HCV is directly involved in hepatocarcinogenesis, albeit other factors such as continued cell death and regeneration associated with inflammation would play a role, as well. The downstream events of the core protein are segregated into two components. One is the augmented production of oxidative stress along with the activation of scavenging system including catalase and glutathion (GSH) in the putative preneoplastic stage with steatosis in the liver. Thus, oxidative stress production in the absence of inflammation by the core protein would partly contribute to the development of HCC. The generation of oxidative stress is estimated to originate from mitochondrial dysfunction in hepatocytes by HCV infection. The other is the alteration of intracellular signaling cascade of MAPK (JNK),AP-1, cyclin D1, and CDK4. The combination of these pathways, collective with HCV-associated alterations in lipid and glucose metabolism, would lead to the frequent development of HCC in persistent HCV infection. Our results suggest that there would be a mechanism for hepatocarcinogenesis in persistent HCV infection that is distinct from those for other cancers. Similar to the pathogenesis of other cancers, the accumulation of a set of genetic aberrations may also be necessary for multistage development of HCC. However, HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple steps to be bypassed in hepatocarcinogenesis. Therefore, unlike other cancers, HCV infection can elicit HCC in the absence of a complete set of genetic aberrations. Such a scenario, "non-Vogelstein-type" carcinogenesis, would explain the unusually high incidence and multicentric nature of HCC development in HCV infection.


TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons.
This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12-24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 microm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls (P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group (P < 0.05). The number of action potentials discharged increased in the TNBS group (P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na(+) and K(+) channels at the soma, which persist after removal from the inflamed environment.


The cecal appendix is correlated with greater maximal longevity in mammals.
The cecal appendix had been considered as a useless vestige since Darwin's work, but recent research questioned this idea demonstrating that the cecal appendix appeared among the mammals at least 80 million years ago and has made multiple and independent appearances without any obvious correlation with diet, social life, ecology, or size of the cecum. However, functions and probable selective advantage conferred by this anatomical structure still remain enigmatic. We found, through analyses of data on 258 mammalian species, that cecal appendix presence is correlated with increased maximal observed longevity. This is the first demonstration of a correlation between cecal appendix presence and life history. Interestingly, the classical evolutionary theory of aging that predicts an increased longevity when the extrinsic mortality is reduced has been questioned several times, but recent comparative studies asserted its validity in the taxa, which experience age-dependent and density-dependent mortality, as in mammals. Thus, the cecal appendix may contribute to the increase in longevity through a reduction of extrinsic mortality. A lower risk of fatal infectious diarrhea is one of the most plausible hypotheses that could explain it. However, several hypotheses coexist about the possible functions of the cecal appendix, and our results provide new insights about this much-disputed question. In addition, we show that the cecal appendix arose at least 16 times and was lost only once during the evolutionary history of the considered mammals, an asymmetry that supports the existence of a positive selective of this structure.


Keeping in touch. Cell phone use in people with schizophrenia disorders.
There is limited research exploring telephone intervention for psychiatric clients; no studies specific to cell phone use have been conducted. This pilot study examined the feasibility and acceptability of cell phone use in individuals with schizophrenia spectrum disorders (SSDs). Ten outpatients with SSDs were provided with previously activated cell phones for 5 months; trained nurses contacted participants weekly. Seven participants completed the 5-month follow-up period. A minority of participants reported difficulty retrieving messages and answering or charging their phone. These preliminary findings indicate the majority of individuals with SSDs are willing to use this method of communication and are able to do so with few problems. Possible barriers to the use of cell phones with this group include lifestyle factors and poor decision making. Future investigations should examine the use of cell phone access to foster personal safety, gain a sense of connectedness to others, and enhance quality of life.


A new mark shearing technique for strain measurement using digital image correlation method.
The digital image correlation (DIC) method is a noncontact, full-field surface deformation measuring method, which is widely used in experimental mechanics. Although the DIC method has a high precision in displacement measurement, its precision in strain determination is a bit low. In this paper, a new mark shearing technique is proposed to improve the accuracy of the strain measurement of the DIC method. A wedge mirror is used to introduce a shearing distance of the marks, which are made on the specimen to calculate the strain. The measurement principle of the mark shearing technique is described in detail. From the analysis, it can be concluded that this method is suitable for both large-scaled and small-scaled specimens, and thus has a wider adaptability than the common DIC method. Using this method, the maximum gauge length is 80 mm, and the accuracy of strain measurement can reach 4 microm strains. A tensile experiment with aluminum sample was conducted, and the successful results demonstrated the feasibility of this method.


Occurrence of paratubal cysts in childhood: An analysis of 26 cases.
A retrospective analysis was conducted on the case files of patients operated on for adnexal pathology between January 2004 and December 2015 at our institution. The data of the patients with a diagnosis of paratubal cysts (PTCs) was extracted. A total of eighty-seven children were operated on for adnexal pathology. Twenty-six (29.9%) patients had PTCs. The patients were predominantly grouped as adolescents (n=22) and newborns (n=3). One of the patients was a pre-pubertal girl. Of the 26 PTC cases, 18 of them occurred on the contralateral side to ovarian pathology (OP) or physiologic ovarian changes (POC) such as corpus luteum cyst or follicular cyst which their final diagnosis confirmed by histopathology examination; in one case, the PTCs were bilateral; and in three cases, PTCs were ipsilateral with OP or POC. There were only 4 solitary PTC cases identified among the 26 cases. Paratubal cysts can be observed at every age, even in newborns. Their association with OP or POC in childhood cases needs to be clarified to further understand the hormonal mechanisms that are influencing the occurrence of these cysts.


Ecological indicators for qualitative assessment of Ojarud River: A case study.
Today, the application of ecological indicators based on organisms has replaced traditional saprobic approaches for assessment of the quality of rivers impaired due to organic pollution and some other environmental disturbances. This study aimed to weigh the quality of the Ojarud River in Ardabil, Iran, applying biological and physiological indices of macro-invertebrates. A total of 12,524 samplings were fulfilled at four stations (S1, S2, S3, S4) from the headstream to downstream by a Surber sampler (30 × 30 cm2) from June/2020 to April/2021. All year round, the highest frequent families were Chironomidae (2658), Simuliidae (1025) from Diptera and Caenidae (1855), and Baetidae (724) from Ephemeroptera. The diversity pattern was analyzed by PAST software, and Primer 7 (BIO-ENV analysis) was utilized to understand what factor has the most impact on the distribution of macro-invertebrates. The least similarity of S4 to other stations was recognized by Cluster analysis. As per the ANOSIM (analysis of similarities), a statistically significant difference in the macroinvertebrates' frequency was established between S3 and other stations (p = .0001, r = .63). Moreover, the relationship between heavy metals and macro-invertebrate showed that the three families of Simuliidae, Gomphidae, and Caenidae had a positive correlation with the concentrations of heavy metals in the sediment. As per the Ephemeroptera, Plecoptera and Trichoptera index, the water quality was placed in the "excellent" class, but the Biological Monitoring Working Party and Hilsenhoff Family Biotic Index indices scored the water quality "good" class at S1 and the "poor" class at S3. Based on the results of this study, the use of physicochemical and hydro-morphological indicators can support the biological indicators but cannot replace them. In addition, careful evaluation of biological indicators is required to develop conservation strategies.


High Resolution Turntable Radar Imaging via Two Dimensional Deconvolution with Matrix Completion.
Resolution is the bottleneck for the application of radar imaging, which is limited by the bandwidth for the range dimension and synthetic aperture for the cross-range dimension. The demand for high azimuth resolution inevitably results in a large amount of cross-range samplings, which always need a large number of transmit-receive channels or a long observation time. Compressive sensing (CS)-based methods could be used to reduce the samples, but suffer from the difficulty of designing the measurement matrix, and they are not robust enough in practical application. In this paper, based on the two-dimensional (2D) convolution model of the echo after matched filter (MF), we propose a novel 2D deconvolution algorithm for turntable radar to improve the radar imaging resolution. Additionally, in order to reduce the cross-range samples, we introduce a new matrix completion (MC) algorithm based on the hyperbolic tangent constraint to improve the performance of MC with undersampled data. Besides, we present a new way of echo matrix reconstruction for the situation that only partial cross-range data are observed and some columns of the echo matrix are missing. The new matrix has a better low rank property and needs just one operation of MC for all of the missing elements compared to the existing ways. Numerical simulations and experiments are carried out to demonstrate the effectiveness of the proposed method.


Leukoregulin-increased plasma membrane permeability and associated ionic fluxes.
The role of ion fluxes in the increased plasma membrane permeability of tumor cells exposed to the anticarcinogenic and tumor cell proliferation inhibitory lymphokine, leukoregulin, was examined by flow cytometic analysis of cell surface perturbations indicative of membrane destabilization. The pI 5.3 form of leukoregulin was isolated by ion exchange, isoelectric focusing, and molecular sizing chromatography of lymphokines from phytohemagglutinin-stimulated normal human lymphocytes. Membrane permeability increased within 5 min of leukoregulin exposure of tumor cells and was quantified by following the efflux of fluorescein or influx of propidium iodide. Membrane permeability increased in proportion to leukoregulin concentration. By 2 h, 0.25-30 units/ml induces a 10-90% change in K562 erythroleukemia cell permeability. Similar changes are effected by Ca2+ ionophores A23187 and X-537A but not by the Na+ ionophore monensin or the K+ ionophore valinomycin. The Ca2+ ionophores and the intracellular Ca2+ mobilizers ouabain and amphotericin B enhance, whereas calmodulin inhibits leukoregulin action. Ca2+ channel blockers nifedipine and verapamil and the Na+ and K+ ion transport inhibitors amiloride and atractyloside, respectively, neither alter membrane permeability nor influence leukoregulin activity. Further evidence for the role of increased Ca2+ flux in leukoregulin's action is provided by detection of increased intracellular free Ca2+ in leukoregulin-treated cells with the Ca2+-sensitive fluorescent probe 2-[2-bis(carboxymethyl)amino-5-methylphenoxy]methyl-6-methoxy-8-bis (carboxymethyl)aminoquinoline. Kinetic analysis of cell volume, forward and right angle light scatter, fluorescein efflux, and propidium iodide influx, moreover, reveals that the action of leukoregulin is unique. Membrane perturbations may be critical initial steps in the ability of leukoregulin to directly prevent the development of carcinogenesis as well as inhibit the continued proliferation of neoplastic cells.


Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays.
A previously unstudied medicinal plant, Leucophyllum frutescens (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer's disease. Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including in vitro enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active n-butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC-MS/MS), and in silico molecular docking by Maestro® Schrödinger. The n-butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The in vivo study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC-MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6'-O-malonate, diosmetin-7-O-glucuronide-3'-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3'-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6'-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase. The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.


Autophagy contributes to sulfonylurea herbicide tolerance via GCN2-independent regulation of amino acid homeostasis.
Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved in SU tolerance. Here, we report a novel SU tolerance mechanism, autophagy, which we call 'homeostatic tolerance,' is involved in amino acid signaling in Arabidopsis. The activation and reversion of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for the activation of autophagy and GCN2. Genetic and biochemical analyses revealed a lower proportion of free BCAA and more sensitive phenotypes in atg5, atg7, and gcn2 single mutants than in wild-type seedlings after TM treatment; the lowest proportion of free BCAA and the most sensitive phenotypes were found in atg5 gcn2 and atg7 gcn2 double mutants. Immunoblotting and microscopy revealed that TM-induced activation of autophagy and GCN2 signaling do not depend on the presence of each other, and these 2 pathways may serve as mutually compensatory mechanisms against TM. TM inhibited the TOR (target of rapamycin), and activated autophagy in an estradiol-induced TOR RNAi line, suggesting that TM-induced BCAA starvation activates autophagy, probably via TOR inactivation. Autophagy and GCN2 were also activated, and independently contributed to TM tolerance in plants conferring metabolic tolerance. Together, these data suggest that autophagy is a proteolytic process for amino acid recycling and contributes to GCN2-independent SU tolerance, probably by its ability to replenish fresh BCAA.


Scallop Shells Exhibit Optimization of Riblet Dimensions for Drag Reduction.
Drag reduction by streamwise surface grooves, or riblets, has been observed by engineers and has been suggested to apply to certain biological systems. Drag reductions as high as 8% have been observed (1), leading to practical nautical and aeronautical applications (2, 3, 4). The shells of several species of scallop, including Placopecten magellanicus, display riblets arranged radially, and therefore roughly parallel to the flow during swimming (Fig. 1a). The dimensions of these riblets on particular scallops fall within the region necessary for drag reduction at experimentally measured swimming speeds. Moreover, the actual spacing of the riblets gradually migrates into the theoretically optimal spacing region as shell length increases beyond 40 mm (Figs. 2, 3). Specimens of P. magellanicus 40 to 80 mm in length demonstrate the greatest swimming ability (5); our data strongly suggest that streamwise riblets may be a contributing factor to the swimming success in scallops of this size range.


Blackbody spectra for sonoluminescing hydrogen bubbles.
The dynamical motion of sonoluminescing bubbles formed from a mixture of water and hydrogen gas indicates that these bubbles contain hydrogen. Their spectrum is well matched by an ideal 6000 K blackbody radiating from a surface with a radius less than 1/4 microm. According to this model, the state of matter inside the collapsed bubble is so stressed that the photon mean free path is much smaller than 1 microm. Implications for various theories of the light-emitting mechanism and the role of chemical reactions are discussed.


Translation of the UK Pediatric Influenza Vaccination Programme in Primary Schools to 13 European Countries Using a Dynamic Transmission Model.
Objectives: To simulate the impact of a pediatric influenza vaccination programme using quadrivalent live attenuated influenza vaccine (QLAIV) in Europe by applying coverage rates achieved in the United Kingdom during the 2014-2015 season and to compare the model outcomes to the UK results. Methods: We used a deterministic, age-structured, dynamic transmission model adapted to the demography, contact patterns and influenza incidence of 13 European countries, with a 10-year horizon. The reference strategy was the unchanged country-specific coverage rate, using quadrivalent inactivated vaccine (assumed efficacy against infection from 45% in 1-year-old children to 60% in healthy adults). In the evaluated strategy, 56.8% of 5-10-year-old children were additionally vaccinated with QLAIV (assumed efficacy 80%), as was the case in 2014-2015 in the United Kingdom's primary school pilot areas. Symptomatic influenza cases and associated medical resources (primary care consultations [PCC], hospitalization, intensive care unit [ICU] admissions) were calculated. The evaluated versus reference strategies were compared using odds ratios (ORs) for PCC in the target (aged 5-10-years) and non-target adult (aged >17 years) populations as well as number needed to vaccinate (NNV) with QLAIV to avert one PCC, hospitalization or ICU admission. Model outcomes, averaged over 10 seasons, were compared with published real-life data from the United Kingdom for the 2014-2015 season. Results: Over 13 countries and 10 years, the evaluated strategy prevented 32.8 million of symptomatic influenza cases (172.3 vs 205.2 million). The resulting range of ORs for PCC was 0.18-0.48 among children aged 5-10-years, and the published OR in the United Kingdom was 0.06 (95% confidence interval [0.01; 0.62]). In adults, the range of ORs for PCC was 0.60-0.91 (UK OR=0.41 [0.19; 0.86]). NNV ranges were 6-19 per averted PCC (UK NNV=16), 530-1524 per averted hospitalization (UK NNV=317) and 5298-15 241 per averted ICU admission (UK NNV=2205). Conclusions: Across a range of European countries, our model shows the beneficial direct and indirect impact of a paediatric vaccination programme using QLAIV in primary school-aged children, consistent with what was observed during a single season in the United Kingdom. Recommendations for the implementation of pediatric vaccination programmes are, therefore, supported in Europe.


Liquid-Crystal and Fire-Retardant Properties of New Hexasubstituted Cyclotriphosphazene Compounds with Two Schiff Base Linking Units.
A series of new hexasubstituted cyclotriphosphazene compounds (4a-j) consisting of two Schiff base linking units and different terminal substituents was successfully synthesized and characterized. The structures of these compounds were confirmed using Fourier Transform Infra-Red (FTIR), Nuclear Magnetic Resonance (NMR), and CHN elemental analysis. Polarized optical microscopy (POM) was used to determine their liquid-crystal behavior, which was then further confirmed using differential scanning calorimetry (DSC). Compounds 4a-i with heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, 4-carboxyphenyl, chloro, and nitro terminal ends, respectively, showed the liquid-crystal properties, whereas compound 4j with the amino group was found to be non-mesogenic. The attachment of an electron-donating group in 4j eventually give a non-mesogenic product. The study of the fire-retardant properties of these compounds was done using the limiting oxygen index (LOI). In this study, polyester resin (PE) was used as a matrix for moulding, and the LOI value of pure PE was 22.53%. The LOI value increased to 24.71% when PE was incorporated with 1 wt.% of hexachlorocyclotriphosphazene (HCCP), thus indicating that HCCP has a good fire-retardant properties. The result showed that all the compounds have good agreement in their LOI values. Compound 4i with a nitro terminal group gave the highest LOI value of 28.37%.


Endoscopic Ultrasound-Guided Liver Biopsy in the Hands of a Chest Physician.
Liver biopsy using transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) has never been described before and biopsies of infradiaphragmatic lesions using this technique are not considered to be standard. A patient suspected for primary lung cancer with multiple lesions in the liver was referred to our department. We conducted bronchoscopy and endobronchial ultrasound-guided (EBUS) biopsy from several enlarged mediastinal lymph nodes. Thereafter, we conducted EUS-B-FNA from a lesion in the left liver lobe. Pathology showed that the liver lesion represented a metastasis from a pulmonary adenocarcinoma. Bronchoscopy and EBUS samples were not able to establish diagnosis. We hereby demonstrated that a diagnostic EUS-B-FNA from a liver metastasis in a patient with lung cancer is possible. This underlines that chest physicians should not forget the esophagus when staging lung cancer.


Patient QA systems for rotational radiation therapy: a comparative experimental study with intentional errors.
The purpose of the present study was to investigate the ability of commercial patient quality assurance (QA) systems to detect linear accelerator-related errors. Four measuring systems (Delta(4®), OCTAVIUS(®), COMPASS, and Epiqa™) designed for patient specific quality assurance for rotational radiation therapy were compared by measuring four clinical rotational intensity modulated radiation therapy plans as well as plans with introduced intentional errors. The intentional errors included increasing the number of monitor units, widening of the MLC banks, and rotation of the collimator. The measurements were analyzed using the inherent gamma evaluation with 2% and 2 mm criteria and 3% and 3 mm criteria. When applicable, the plans with intentional errors were compared with the original plans both by 3D gamma evaluation and by inspecting the dose volume histograms produced by the systems. There was considerable variation in the type of errors that the various systems detected; the failure rate for the plans with errors varied between 0% and 72%. When using 2% and 2 mm criteria and 95% as a pass rate the Delta(4®) detected 15 of 20 errors, OCTAVIUS(®) detected 8 of 20 errors, COMPASS detected 8 of 20 errors, and Epiqa™ detected 20 of 20 errors. It was also found that the calibration and measuring procedure could benefit from improvements for some of the patient QA systems. The various systems can detect various errors and the sensitivity to the introduced errors depends on the plan. There was poor correlation between the gamma evaluation pass rates of the QA procedures and the deviations observed in the dose volume histograms.


Creep Monitoring of Submersible Observation Windows Using Mueller Matrix Imaging.
Safety of the observation window is one of the core concerns for manned submersibles. When subjected to underwater static pressure, extrusion and creep deformation always occur in the observation window, which can pose a threat to both safety and optical performance. To assess the deformation, real-time and non-contact monitoring methods are necessary. In this study, a conceptual setup based on the waveplate rotation and dual-DoFP (division of focal-plane polarimeter) polarization camera is built for the observation window's creep monitoring by measuring the Mueller matrix images of the samples under different pressures and durations. Then, a series of characteristic parameters, such as t1, R, r, R', are extracted from the Muller matrix images by Mueller matrix transformation (MMT), Mueller matrix polar decomposition (MMPD), correlation analysis and phase unwrapping method. The results demonstrate that these parameters can effectively describe the observation window's creep at different pressure levels which are simulated by finite element analysis. Additionally, more characterization parameters, such as ψ, A and D, are given from the Mueller matrix images and discussed to illustrate the method's potential for further applications and investigations. Ultimately, future devices based on this method could serve as a valuable tool for real-time and non-contact creep monitoring of the submersible observation windows.


Cloning of murine translation initiation factor 6 and functional analysis of the homologous sequence YPR016c in Saccharomyces cerevisiae.
The cDNA sequence of a murine gene whose expression was up-regulated after epidermal injury was cloned utilizing differential display. The full-length cDNA was isolated by 3' and 5' rapid amplification of cDNA ends from mouse liver. The predicted protein is >97% identical to the human sequence for eukaryotic translation initiation factor (eIF) 6, thus identifying the gene as murine eIF6. Functional studies of the yeast eIF6 homolog, YPR016c, were initiated in Saccharomyces cerevisiae to determine the cellular role(s) of eIF6. Complete deletion of the YPR016c coding sequence was lethal. Viability was restored in the presence of either YPR016c or murine eIF6, when either was expressed as amino-terminal green fluorescent protein fusion protein. Moreover, both fusion proteins localized to nuclear/perinuclear compartments in their respective yeast strains. When the expression of YPR016c-green fluorescent protein was repressed, there was a dramatic reduction in the 60 S ribosomal subunit and polysome content and decreased 80S monosome content. Additionally, the YPR016c-depleted cells arrested in G1. These studies show that YPR016c, which encodes yeast eIF6, is necessary for maximal polysome formation and plays an important role in determining free 60 S ribosomal subunit content.


Identification and characterization of the genes for mitochondrial ribosomal proteins of Saccharomyces cerevisiae.
We have purified 13 large subunit proteins of the mitochondrial ribosome of the yeast Saccharomyces cerevisiae and determined their partial amino acid sequences. To elucidate the structure and function of these proteins, we searched for their genes by comparing our sequence data with those deduced from the genomic nucleotide sequence data of S. cerevisiae and analyzed them. In addition, we searched for the genes encoding proteins whose N-terminal amino acid sequences we have reported previously [Grohmann, L., Graack, H.-R., Kruft, V., Choli, T., Goldschmidt-Reisin, S. & Kitakawa, M. (1991) FEBS Lett. 284, 51-56]. Thus, we were able to identify and characterize 12 new genes for large subunit proteins of the yeast mitochondrial ribosome. Furthermore, we determined the N-terminal amino acid sequences of seven small subunit proteins and subsequently identified the genes for five of them, three of which were found to be new.


Identification of non-macrocyclic small molecule inhibitors against the NS3/4A serine protease of hepatitis C virus through in silico screening.
Drug discovery and design for inhibition of the Hepatitis C Virus (HCV) NS3/4A serine protease is a major challenge. The broad, shallow, and generally featureless nature of the active site makes it a difficult target for "hit" selection especially using standard docking programs. There are several macrocyclic NS3/4A protease inhibitors that have been approved or are in clinical trials to treat chronic HCV (alone or as combination therapy), but most of the current therapies for HCV infection have untoward side effects, indicating a continuing medical need for the discovery of novel therapeutics with improved efficacy. In this study, we designed and implemented a two-tiered and progressive docking regime that successfully identified five non-macrocyclic small molecules that show inhibitory activity in the low micromolar range. Of these, four compounds show varying inhibition against HCV subgenotypes 1b, 1a, 2a, and 4d. The top inhibitor (3) has an IC(50) value of 15 μM against both subgenotypes 1b and 2a of the NS3/4A protease enzyme. Another inhibitor, 1, inhibits all four subgenotypes with moderate activity, showing highest activity for genotype 2a (24 μM). The five inhibitors presented in this study could be valuable candidates for future hit to lead optimization. Additionally, enzyme-inhibitor interaction models presented herein provide key information regarding structural differences between the active sites of the NS3/4A protease of the HCV subgenotype 1a and 1b that might explain the variable inhibitory activity between subgenotypes of the small molecule inhibitors identified here.