BEEF SPECIES SYMPOSIUM: Can we build the cowherd by increasing longevity of females?
Increasing longevity of beef cows by decreasing the proportion culled due to reproductive failure provides an efficient process to rebuild a cow herd and can reduce number of replacements needed to sustain a constant herd size. Rate of reproductive failure varies due to cow age, where failure in cows 2 to 4 yr of age is often greater than in cows 5 to 7 yr of age. In addition, BW of cow and calf at weaning increase as cows advance from 2 to 5 yr of age. The cumulative effect of increasing retention of young cows is improved production efficiency through decreased replacement rate and changing age structure of the herd resulting in a greater proportion of cows at maximal production potential for calf BW at weaning and cow BW at time of culling. Calculations from cow age-specific culling and BW data from commercial and research herds indicated that reducing replacement rate from 18% to 14% resulted in a 23% increase in calf BW weaned and a 2% increase in cull cow BW per pregnant replacement heifer going into the herd. Although improving longevity increases production efficiency, genetic advancement in sustained reproductive function is challenging, as it is the sequential culmination of the annual repetition of numerous discrete physiological processes, each ending in a qualitative response. Successful completion of one process is prerequisite to evaluating subsequent processes. These physiological processes are subject to nutritional threshold requirements that may vary due to genetic potential for other production traits such as milk, growth, and mature size resulting in genetic-by-nutrition interactions. This is in contrast to most traits for which EPD exist, where genetic-by-environment interactions are not considered to be significant. Extensive research concerning impact of limited nutrition on reproduction has led to recommendations that heifers and cows be fed to a threshold BW or BCS to ensure reproductive success; a process that masks nutritional interactions that might otherwise result in reproductive failure. This management approach minimizes selection for animals capable of sustained reproductive function under limited nutritional environments. Rearing and managing cows under nutritionally limited environments may lead to adaptations that result in relatively high levels of reproductive success under lower input levels. Such adaptation may improve chances for longer retention in their offspring in nutrient-limited environments.


Secretory carrier membrane protein 5 is an autophagy inhibitor that promotes the secretion of α-synuclein via exosome.
Autophagy-lysosomal pathway is a cellular protective system to remove aggregated proteins and damaged organelles. Meanwhile, exosome secretion has emerged as a mode to selectively clear the neurotoxic proteins, such as α-synuclein. Mounting evidence suggests that these two cellular processes are coordinated to facilitate the clearance of toxic cellular waste; however the regulators for the transition between these two processes are unclear. Here we show that SCAMP5, a secretory carrier membrane protein significantly induced in the brains of Huntington's disease patients, is quickly and transiently induced by protein stress and autophagic stimulation, and is regulated by the master autophagy transcriptional regulator TFEB. Ironically, SCAMP5 inhibits autophagy flux by blocking the fusion of autophagosomes and lysosomes. Although autophagy is blocked, SCAMP5 does not cause significant protein aggregation in cells. Instead, it promotes the Golgi fragmentation and stimulates the unconventional secretion of the co-localizing α-synuclein via exosome as an exosome component. Therefore, we have identified SCAMP5 as a novel coordinator of autophagy and exosome secretion, which is induced upon protein stress to channel the efficient clearance of toxic proteins via the exosomes rather than autophagy-lysosomal pathway.


MicroRNA-27a is induced by leucine and contributes to leucine-induced proliferation promotion in C2C12 cells.
Leucine, a branched chain amino acid, is well known to stimulate protein synthesis in skeletal muscle. However, the role of leucine in myoblast proliferation remains unclear. In this study, we found that leucine could promote proliferation of C2C12 cells. Moreover, expressions of miR-27a and myostatin (a bona fide target of miR-27a) were upregulated and downregulated, respectively, following leucine treatment. We also found that miR-27a loss-of-function by transfection of a miR-27a inhibitor suppressed the promotion of myoblast proliferation caused by leucine. Our results suggest that miR-27a is induced by leucine and contributes to leucine-induced proliferation promotion of myoblast.


Comparing the effectiveness of two app-based number lines to teach price comparison to students with autism spectrum disorders.
A number line consisting of Arabic numerals is a commonly used instructional tool for teaching price comparison. However, typical number lines lack concrete visual cues, which may benefit students with autism spectrum disorders (ASD) who have not yet mastered the representation of Arabic numerals. This study investigated the effects of additional visual cues (i.e., dots) by comparing two types of app-based number line conditions: number lines with and without dots. A single-subject, alternating treatment design study was employed across five secondary students with ASD. Both number line conditions were effective for four of the students in assisting them to select cheaper items and complete task analysis steps. The number line with dots was effective or slightly more effective in selecting smaller numbers for three of the students. The findings of this study support the literature on the use of number lines as an effective tool to assist students in price comparison. The benefits of adding concrete visual cues and other teaching strategies (e.g., the holistic and decomposition models) were discussed. Implications for Rehabilitation This study investigated the effectiveness of concrete visual cues, such as dots, on a number line app for teaching students with ASD who had not yet developed the association of quantities with the numerals. We found that incorporation of a hybrid number comparison model - first holistic (for whole numbers) and then decomposition (for numbers after the decimal point) - is effective when teaching students how to compare prices with an uneven number of digits. This study provides an alternative for special education teachers to schedule practice, such as the use of simulated settings to achieve mastery, then transitioning to community-based settings to test skill generalization.


Fatty acid composition indicates two types of metabolic syndrome independent of clinical and laboratory parameters.
Dietary composition and metabolism of fatty acids (FA) influence insulin resistance, atherogenic dyslipidemia and other components of the metabolic syndrome (MS). It is known that patients with MS exhibit a heterogeneous phenotype; however, the relationships of individual FA to MS components have not yet been consistently studied. We examined the plasma phosphatidylcholine FA composition of 166 individuals (68F/98M) with MS and of 188 (87F/101M) controls. Cluster analysis of FA divided the groups into two clusters. In cluster 1, there were 65.7 % of MS patients and 37.8 % of controls, cluster 2 contained 34.3 % of patients and 62.2 % of controls (P<0.001). Those with MS within cluster 1 (MS1) differed from individuals with MS in cluster 2 (MS2) by concentrations of glucose (P<0.05), NEFA (P<0.001), HOMA-IR (P<0.05), and levels of conjugated dienes in LDL (P<0.05). The FA composition in MS1 group differed from MS2 by higher contents of palmitoleic (+30 %), gamma-linolenic (+22 %), dihomo-gamma-linolenic (+9 %) acids and by a lower content of linoleic acid (-25 %) (all P<0.01). These FA patterns are supposed to be connected with the progression and/or impaired biochemical measures of MS (lipolysis, oxidative stress, dysglycidemia, and insulin resistance).


Is SpxA2 involved in hydrogen peroxide production and competence development in Streptococcus sanguinis?
The objective of the present study was to investigate whether Streptococcus sanguinis SpxA2 plays a role in competence development and endogenous H2O2 generation, and whether the SpxA2 Cys10-XX-Cys13 (CXXC) motif is involved in competence development. The competence development of wild-type S. sanguinis (SK36) and its derivatives was compared by transformation efficiency assay and real-time RT-PCR. The spx allele mutants, spxA2 (C10A) and spxA2 (C13A), were constructed by site-directed mutagenesis. The Δpox mutant was treated with 1 mM H2O2 to exclude the effect of other Pox products on competence development. Compared with the wild-type (4.42±0.58×10-4), the ΔspxA2 mutant showed decreased transformation efficiency (0.07±0.03×10-4). Furthermore, there was a 2- to 15-fold reduction in ΔspxA2 mutant com gene expression. SpxA2 was able to down-regulate endogenous H2O2 generation by repressing pox expression. Additionally, endogenous H2O2 negatively regulated competence without affecting spxA2 expression. The Δpox mutant increased com gene expression (2- to 8-fold), but the 1 mM H2O2-treated Δpox mutant showed decreased com gene expression. Interestingly, the ΔspxA2Δpox mutant showed enhanced competence-associated parameters. The fact that spxA2 (C10A) and spxA2 (C13A) behaved like the ΔspxA2 mutant revealed the role of the CXXC motif in competence development. Although the intricate relationship between SpxA2, pox-mediated H2O2 production and competence development was clarified in S. sanguinis, it would be worthwhile to explore further whether H2O2 is involved in competence development through oxidizing the SpxA2 CXXC motif.


The relationship between the number of erupted primary teeth and the child's height and weight: a cross-sectional study.
The objective of this study is to determine the correlation between the number of erupted primary teeth, the age, sex and the somatic measures of weight and height (length) in a Brazilian population based cross sectional study. A systematic sampling was used. Complete and consistent data were obtained from 870 of a total of 908 children from birth to 36 months of age. Statistical analysis comprised a multiple regression equation, where the number of erupted primary teeth was modeled as the dependent variable and the initial specification included the following independent variables: age, sex, birth-length, birth-weight, weight and length measured at the examination of the child. Results showed that in this study, 86% of the variation of the number of erupted primary teeth was explained by age and height of children (p < 0.001). Age and height showed a stronger correlation with the number of erupted primary teeth than all the tested variables together. It was concluded that primary teeth eruption is highly influenced by age and height (length) of the child. Using the best regression equation found, a chart was constructed where the variation of the number of erupted primary teeth is given according to age and height of the child.


Nutraceuticals to promote neuronal plasticity in response to corticosterone-induced stress in human neuroblastoma cells.
Objectives: To search for novel compounds that will protect neuronal cells under stressed conditions that may help to restore neuronal plasticity. Methods: A model of corticosterone (CORT)-induced stress in human neuroblastoma cells (SH-SY5Y) was used to compare the efficacy of 6 crude extracts and 10 pure compounds (6 polyphenols, 2 carotenoids, 1 amino acid analogue, and 1 known antidepressant drug) to increase neuronal plasticity and to decrease cytotoxicity. Results: Astaxanthin (among pure compounds) and phlorotannin extract of Fucus vesiculosus (among crude extracts) showed a maximum increase in cell viability in the presence of excess CORT. BDNF-VI mRNA expression in SH-SY5Y cells was significantly improved by pretreatment with quercetine, astaxanthin, curcumin, fisetin, and resveratrol. Among crude extracts, xanthohumol, phlorotannin extract (Ecklonia cava), petroleum ether extract (Nannochloropsis oculata), and phlorotannin extract (F. vesiculosus) showed a significant increase in BDNF-VI mRNA expression. CREB1 mRNA expression was significantly improved by astaxanthin, β-carotene, curcumin, and fluoxetine whereas none of the crude extracts caused significant improvement. As an adjunct of fluoxetine, phlorotannin extract (F. vesiculosus), β-carotene, and xanthohumol have resulted in significant improvement in BDNF-VI mRNA expression and CREB1 mRNA expression was significantly improved by phlorotannin extract (F. vesiculosus). Significant improvement in mature BDNF protein expression by phlorotannin extract (F. vesiculosus) and β-carotene as an adjunct of fluoxetine confirm their potential to promote neuronal plasticity against CORT-induced stress. Discussion: The carotenoids, flavonoids, namely quercetine, curcumin, and low molecular weight phlorotannin-enriched extract of F. vesiculosus may serve as potential neuroprotective agents promoting neuronal plasticity in vitro. Graphical abstract: Cascade of events associated with disturbed homeostatic balance of glucocorticoids and impact of phlorotannin extract (F. vesiculosus) and β-carotene in restoring neuronal plasticity. Abbreviation: TrKB, tropomyosin receptor kinase B; P-ERK, phosphorylated extracellular signal-related kinase; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; Ca++/CaMK, calcium/calmodulin-dependent protein kinase; pCREB, phosphorylated cAMP response element-binding protein; CRE, cAMP response elements, CORT, corticosterone; and BDNF; brain-derived neurotrophic factor.


A roadmap to clinical trials for FLASH.
While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous dosimetry, 3D treatment planning, volumetric image guidance, or motion management, may play a major role in defining how to use, or whether to use, FLASH radiotherapy. Given the extended time frame for patients to experience late effects, we recommend moving deliberately but cautiously forward toward clinical trials. In this paper, we review the state of quality assurance and safety systems in FLASH, identify critical pre-clinical data points that need to be defined, and suggest how lessons learned from previous technological advancements will help us close the gaps and build a successful path to evidence-driven FLASH implementation.


Multifocal intraepithelial neoplasia and the psychological consequence of vulvectomy.
A 41-year-old female with significant psychiatric history presented with persistent vulvar lesions that were refractory to common clinic and home based wart therapies. Vulvoscopy directed biopsies confirmed invasive vulvar squamous cell carcinoma and further investigation revealed cervical and anal intraepithelial neoplasia in a patient who remained HIV negative with no other cause of immunosuppression detected other than smoking. Vulvectomy following cancer diagnosis lead to a relapse of her psychiatric illness and excessive alcohol intake. Her psychiatric illness in turn affected her further management and follow-up. This case highlights the need for the case based, medical, surgical, psychological and social considerations when managing persistent anogenital warts and anogenital neoplasia as well as the psychological impact of vulvectomy.


Evidence report on the occurrence, assessment, and treatment of depression in cancer patients.
This evidence-based report reviews the empiric literature on depression in people with cancer with a focus on three areas: occurrence, assessment, and treatment. More than 350 studies were identified through searches of the English-language literature published between 1966 and September 2001. Reports of occurrence are limited to prevalence studies, and prevalence rates vary widely despite standardized assessments. Rates of major depressive disorder and depressive symptoms comorbid with cancer appear to be 10%-25%. Although multiple instruments are available for assessing depressive symptoms, a clinical interview using Diagnostic and Statistical Manual of Mental Disorders criteria is the standard to which assessments are compared. Some data exist for the efficacy of psychosocial and pharmacologic treatments for depression in this population. No randomized, controlled studies of alternative medicine interventions were identified.


Comparative histopathology of two serotypes of infectious bronchitis virus (T and n1/88) in laying hens and cockerels.
The comparative and sequential histopathology of different tissues of unvaccinated laying hens and cockerels were studied in chickens exposed to T and N1/88 strain of infectious bronchitis virus (IBV). The Harderian gland and trachea of hens and cockerels in both T- and N1/88-infected groups were damaged to a similar extent. The cecum was unaffected for both strains of IBV in both hens and cockerels. The sequential histopathological changes in hens revealed that IBV multiplies initially in the Harderian gland, then in the tracheal mucosa and simultaneously in the kidney and regions of the oviduct such as the magnum, tubular shell gland, and shell gland pouch. In cockerels, IBV multiplies first in the Harderian gland, then simultaneously in the trachea and kidney. Overall, the severity and persistence of lesions were greater in the kidneys of T-infected hens as compared with N1/88-infected hens. However, pathological changes in the kidney were mild in T- and N1/88-infected cockerels.


Experimental validation of calculated atomic charges in ionic liquids.
A combination of X-ray photoelectron spectroscopy and near edge X-ray absorption fine structure spectroscopy has been used to provide an experimental measure of nitrogen atomic charges in nine ionic liquids (ILs). These experimental results are used to validate charges calculated with three computational methods: charges from electrostatic potentials using a grid-based method (ChelpG), natural bond orbital population analysis, and the atoms in molecules approach. By combining these results with those from a previous study on sulfur, we find that ChelpG charges provide the best description of the charge distribution in ILs. However, we find that ChelpG charges can lead to significant conformational dependence and therefore advise that small differences in ChelpG charges (<0.3 e) should be interpreted with care. We use these validated charges to provide physical insight into nitrogen atomic charges for the ILs probed.


Cutaneous and subcutaneous endometriosis. Surgical and hormonal therapy.
Cutaneous or subcutaneous endometriosis is a rare entity that should be suspected in any female presenting with cyclic pain emanating from a mass in the vicinity of an abdominal surgical scar or the umbilicus. The purpose of this report is to examine the diagnostic procedures for endometriosis and to review the therapeutic value of surgical excision alone or in combination with hormonal treatment. Endometriosis presenting cutaneously in an infraumbilical laparoscopy scar and endometriosis occurring subcutaneously in a cesarean section scar were both diagnosed via incisional biopsy. Both lesions were treated with hormonal therapy followed by surgical excision. Hormonal therapy with danazol or with leuprolide resulted in reduction of symptoms but was associated with amenorrhea in both cases and with dyspareunia in the second patient. Subsequent laparoscopy and surgical excision of the endometrioma were curative. Preoperative hormonal therapy, although sometimes associated with such side effects as amenorrhea, may be used in cases of large endometriotic masses to reduce the size of the surgical defect, but surgical excision remains the treatment of choice.


Thoracoscopic esophagectomy for intrathoracic esophageal cancer.
Thoracoscopic approaches for esophageal cancer are still disparate. Complete scopic technique is feasible for esophagectomy. Mini-thoracotomy is effective for excellent exposure of the mediastinum for lymph node dissection. The magnifying effect of a video, by keeping the camera in close proximity to the dissection is essential to perform the same quality of dissection as open surgery. The benefit, for respiratory morbidity, remains to be studied in a large number of patients. Minimizing the chest wall injury contributed, to the reduction of constrictive pulmonary damage. Survival after the thoracoscopic approach was favorably compared with open surgery, when extensive lymphadenectomy was performed. Because the efficacy improves with the surgeon's experience, satisfactory outcome will only be obtained in a center performing a sufficient volume of esophageal surgery to provide the surgeon with opportunities to refine his necessary skills. Improvements in technique and instrumentation should make the procedure more accessible and steepen the learning curve.


Quasi-analytic formalism for mode characteristics in highly overmoded rectangular dielectric waveguide bends.
A fast and simple quasi-analytic method to simulate mode characteristics in highly overmoded rectangular dielectric waveguide bends is presented. Fast mode-based bend models are necessary, since overmoded rectangular waveguides have become very popular in optical interconnects on printed circuit boards. The proposed method combines a simple mode solver with the formalism that was proposed by Melloni et al. [J. Lightwave Technol. 16, 571 (2001)], yielding to a very convenient and accurate quasi-analytic formalism for the bend transfer function based on matrix notation. For that purpose, a simple method to approximate leaky modes is introduced. The model offers the ability to predict individual modal phases and amplitudes within a given bend as well as the calculation of coupling losses and was validated using three-dimensional beam-propagation-method simulation software.


Pigmented villonodular synovitis of the temporomandibular joint: a rare tumor of the temporal skull base.
Musculoskeletal tumors are not usually encountered at the skull base. Benign lesions such as cholesterol granuloma, cholesteatoma, fibrous dysplasia, and Paget disease are common examples of such tumors arising from the bone of the cranial base. The authors report a case involving an adult male patient with the rare finding of pigmented villonodular synovitis of the temporomandibular joint. This case is reported as an example of another lesion to consider in the differential diagnosis. Due to the complexity of the anatomy at the cranial base, radical resection as recommended for the usual sites of occurrence in major joints is problematic. Because of the reported high recurrence rates at other sites, as radical excision as possible with vigilance for recurrence is recommended.


An efficient expression, purification and immunodetection system for recombinant gene products.
We describe a modification of the mammalian expression vector pRc/CMV, which drives expression of inserted genes from either the human cytomegalovirus (CMV) immediate-early promoter or the bacteriophage T7 RNA polymerase promoter. The modification is designed to allow expression, simple purification and specific immunodetection of recombinant fusion proteins. The modified plasmid, termed pTag/CMV-neo, encodes a Kozak consensus ribosome-binding site (RBS) and a 30-amino acid fusion tag peptide. This peptide consists of a metal ion-binding site, (His)6, for single-step affinity purification using Ni(2+)-chelating resin and a multi-purpose HIV-1-derived peptide (p18HIV). This viral epitope can be used to identify, detect and characterize target fusion proteins in conjunction with a specific monoclonal antibody H902 that does not display cross-reactivity with cellular proteins. The H902 production hybridoma cell line is reagent #521 from the NIH AIDS Research and Reference Program.


Structural relaxation phenomena in silicate glasses modified by irradiation with femtosecond laser pulses.
Structural relaxation phenomena in binary and multicomponent lithium silicate glasses were studied upon irradiation with femtosecond (fs) laser pulses (800 nm central wavelength, 130 fs pulse duration) and subsequent thermal annealing experiments. Depending on the annealing temperature, micro-Raman spectroscopy analyses evidenced different relaxation behaviours, associated to bridging and non-bridging oxygen structures present in the glass network. The results indicate that the mobility of lithium ions is an important factor during the glass modification with fs-laser pulses. Quantitative phase contrast imaging (spatial light interference microscopy) revealed that these fs-laser induced structural modifications are closely related to local changes in the refractive index of the material. The results establish a promising strategy for tailoring fs-laser sensitivity of glasses through structural mobility.


Perceptions of Gender Violence in Spanish Adolescents.
Gender violence among adolescents is a global problem. In the context of public healthcare, nursing professionals play an important role. The aim of this study was to determine awareness, information, and beliefs regarding gender violence in adolescents and identify their educational needs. Data from a study conducted by the Spanish Centre for Sociological Research and the Government Office for Gender Violence in 2013 are used. The sample contained 698 adolescents aged 15-19 years. This is a secondary analysis of a data survey. Strengthening the Reporting of Observational Studies in Epidemiology guidelines are followed. Sociodemographic variables and seven topics of interest were analyzed: gender inequality, intimate relationships, definition of abuse, identification of abuse, awareness of cases of abuse in women, and informal and formal support networks. The results show that adolescents are well informed, are aware of informal and formal support networks, use the word "respect," identify abuse and consider it unacceptable, and believe media coverage is useful in giving visibility to gender violence. No significant differences were found in gender, social class, or education, and their idea of romantic love remains intact. The researchers conclude that, in Spain, adolescents' awareness of gender violence is strongly influenced by environmental and cultural factors, because of the prevalence of gender and intimate partner violence in the country. Formal interventions such as health education provided by either nursing professionals in schools or the broader community can have a positive effect on adolescent health. Primary care nurses should use these findings to support the development of health promotion programs for young adults.


The role of social network, social support, religiosity and depression among elderly Malaysians who had experienced major life events.
Research has found that social network, social support and religiosity are associated with depression in elderly people. However, these predictors of depression have not been fully explored among the high risk elderly population. This study aims to examine the prevalence and factors associated with depression among Malaysian elderly subjects who had experienced major life events. This is a cross-section study of a subsample of 594 participants from the original sample of 2322 Malaysian elderly respondents, who had experienced major life events. Information on socio-demographic, social network, social support, religiosity and depression were collected through an interviewer-administered questionnaire. A multiple linear regression analysis was used to determine the factors associated with depression among elderly who experienced major life events. Overall prevalence of depression among subsample of Malaysian elderly facing major life events was 9.4%. The results showed that age (p≤0.01), income (p≤0.001) and social network (p≤0.05) were significant associated with depression. In other words, with increasing age, low income as well as small social network associated with high risk of developing depression among elderly who had experienced major life events CONCLUSION: Other than age and income, social network were also associated with depression among elderly respondents who had experienced major life events. Therefore, professionals who are working with elderly with major life events should seek ways to enhance elderly networking as one of the strategies to prevent depression.


Nursing students' mathematic calculation skills.
This mixed method study used a pre-test/post-test design to evaluate the efficacy of a teaching strategy in improving beginning nursing student learning outcomes. During a 4-week student teaching period, a convenience sample of 54 sophomore level nursing students were required to complete calculation assignments, taught one calculation method, and mandated to attend medication calculation classes. These students completed pre- and post-math tests and a major medication mathematic exam. Scores from the intervention student group were compared to those achieved by the previous sophomore class. Results demonstrated a statistically significant improvement from pre- to post-test and the students who received the intervention had statistically significantly higher scores on the major medication calculation exam than did the students in the control group. The evaluation completed by the intervention group showed that the students were satisfied with the method and outcome.


Hemoglobin based oxygen carriers: how much methemoglobin is too much?
The oxidized form of hemoglobin, methemoglobin, is unable to deliver oxygen to tissues. Hemoglobin based oxygen carriers generally lack the natural oxidative-reductive machinery present within the red blood cell that converts methemoglobin to hemoglobin. This study examines tolerable levels of methemoglobin that can be present in solutions of polyethylene glycol (PEG) conjugated bovine hemoglobin without compromising its ability to deliver oxygen. Rodents were exchange-transfused to 30% of their estimated blood volume with solutions of six grams percent PEG-hemoglobin containing varying concentrations of PEG-methemoglobin. Tissue oxygenation was measured by an oxygen dependant phosphorescence quenching method. This study also looked at the level of methemoglobin formation following a top loaded infusion of low methemoglobin containing PEG-hemoglobin. Results of the oxygenation study showed that PEG-methemoglobin levels at or below 10% did not significantly alter the ability of solutions to deliver oxygen to intestines, liver, spleen and kidney. However, PEG-methemoglobin levels greater than 10% resulted in a significant decrease in PEG-hemoglobin's ability to oxygenate tissues. In addition, methemoglobin levels remain low (< 10%) for a substantial period of time following PEG-hemoglobin administration.


The clinical correlation of temporal bone fractures and spiral computed tomographic scan: a prospective and consecutive study at a level I trauma center.
Undetected temporal bone fractures (TBFs) can lead to complications such as hearing loss, facial nerve paralysis, otorrhea, or otorhinorrhea, and can be the cause of life-threatening bacterial meningitis and can easily be missed. We prospectively studied patients with head trauma between January 2000 and January 2001. All patients were examined by the attending trauma physician and then underwent cranial helical computed tomographic (CT) scan independent of clinical findings and Glasgow Coma Scale (GCS) score to determine the proportion of TBFs that would have been missed if diagnosis had been based only on clinical evaluation. Three-hundred fifty consecutive patients with head trauma were studied during the 12-month period (GCS score: range, 3-15; median, 13). In 34 (9.7%) of these patients, 38 TBF (30 unilateral and 4 bilateral) were diagnosed by CT scan. However, clinical signs of TBF were present in only 22 of the 34 patients (65%). All missed TBFs were unilateral. Of the patients with missed TBFs, 8 of 20 (40%) had GCS scores of 14 to 15, 1 of 8 (12.5%) had a GCS score of 9 to 13, and 3 of 6 (50%) had GCS scores < 9. Four of 34 (12%) patients developed clinical complications. TBFs are common injuries in patients with head trauma. More than one third of these fractures may be missed by clinical diagnosis alone. Although the clinical importance of the missed TBF is debatable, 12% of our patients developed complications. Therefore, to rule out these lesions, routine cranial helical CT scan should be recommended in all patients presenting with head trauma, independent of clinical findings and GCS score.


Similarity scaling of pressure fluctuation in turbulence.
Pressure fluctuation was measured in a turbulent jet using a condenser microphone and piezoresistive transducer. The power-law exponent and proportional constant of normalized pressure spectrum are discussed from the standpoint of Kolmogorov universal scaling. The clear power law with scaling exponent close to -7/3 was confirmed in the range of 600<or=R(lambda). These Reynolds numbers are much larger than those in velocity fluctuation to achieve Kolmogorov scaling. The spectral constant is not universal but depends on Reynolds numbers. Measured pressure probability density functions are compared with direct numerical simulation.


Regenerative Potential of Granulation Tissue in Periodontitis: A Systematic Review and Meta-analysis.
Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses. The evidence suggested that cells derived from periodontitis granulation tissue have osteogenic, adipogenic, chondrogenic, neurogenic, and angiogenic differentiation abilities as well as immunoregulatory properties. In particular, CD44+, CD73+, CD90+, CD105+, and CD146+ cells were found widely in granulation tissue whilst the only meta-analysis confirmed that CD90+ cells were present in lower numbers within the granulation tissue when compared with healthy periodontal tissue (WMD = -23.43%, 95% CI -30.43 to -16.44, p < 0.00001). This review provided further evidence that granulation tissue from patients with periodontitis can be a potential stem cell source for regenerative therapy.


Orai1 promotes tumor progression by enhancing cancer stemness via NFAT signaling in oral/oropharyngeal squamous cell carcinoma.
Emerging evidence indicates that Orai1, a key calcium channel for store-operated Ca2+ entry, is associated with human cancer. However, the underlying mechanism by which Orai1 regulates cancer progression remains unknown. Here we report that intracellular level of Orai1 is increased in a stepwise manner during oral/oropharyngeal carcinogenesis and highly expressed in cancer stem-like cell (CSC)-enriched populations of human oral/oropharyngeal squamous cell carcinoma (OSCC). Ectopic Orai1 expression converted non-tumorigenic immortalized oral epithelial cells to malignant cells that showed CSC properties, e.g., self-renewal capacity, increased ALDH1HIGH cell population, increased key stemness transcription factors, and enhanced mobility. Conversely, inhibition of Orai1 suppressed tumorigenicity and CSC phenotype of OSCC, indicating that Orai1 could be an important element for tumorigenicity and stemness of OSCC. Mechanistically, Orai1 activates its major downstream effector molecule, NFATc3. Knockdown of NFATc3 in the Orai1-overexpressing oral epithelial cells abrogates the effect of Orai1 on CSC phenotype. Moreover, antagonist of NFAT signaling also decreases CSC phenotype, implying the functional importance of Orai1/NFAT axis in OSCC CSC regulation. Our study identifies Orai1 as a novel molecular determinant for OSCC progression by enhancing cancer stemness, suggesting that inhibition of Orai1 signaling may offer an effective therapeutic modality against OSCC.


Evaluation of Two Protein Extraction Protocols Based on Freezing and Mechanical Disruption for Identifying Nontuberculous Mycobacteria by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry from Liquid and Solid Cultures.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has proved to be a useful diagnostic method for identifying conventional bacteria. In the case of mycobacteria, a good protein extraction protocol is essential in order to obtain reliable identification results. To date, no such protocol has been definitively established. The aim of this study was to compare the manufacturer's recommended protein extraction protocol (protocol A) with two novel protocols (protocols B and C), which apply different freezing temperatures and mechanical disruption times using an automatic tissue homogenizer. A total of 302 clinical isolates, comprising 41 nontuberculous mycobacteria (NTM) species, were grown in parallel on solid and liquid media and analyzed: 174 isolates were slow-growing mycobacteria (SGM) and 128 isolates were rapid-growing mycobacteria (RGM). Overall, MALDI-TOF MS identified a higher number of NTM isolates from solid than from liquid media, especially with protocol C (83.4 and 68.2%, respectively; P < 0.05). From solid media, this protein extraction method identified 57.9 and 3.9% more isolates than protocols A (P < 0.001) and B (P < 0.05), respectively. In the case of liquid media, protocol C identified 49.7 and 6.3% more isolates than protocols A and B, respectively (P < 0.001). With regard to the growth rate, MALDI-TOF MS identified more RGM isolates than SGM isolates in all of the protocols studied. In conclusion, the application of freezing and automatic tissue homogenizer improved protein extraction of NTM and boosted identification rates. Consequently, MALDI-TOF MS, which is a cheap and simple method, could be a helpful tool for identifying NTM species in clinical laboratories.


Desmoglein-2 expression is an independent predictor of poor prognosis patients with multiple myeloma.
Multiple myeloma (MM) is the second most common haematological malignancy and is an incurable disease of neoplastic plasma cells (PC). Newly diagnosed MM patients currently undergo lengthy genetic testing to match chromosomal mutations with the most potent drug/s to decelerate disease progression. With only 17% of MM patients surviving 10-years postdiagnosis, faster detection and earlier intervention would unequivocally improve outcomes. Here, we show that the cell surface protein desmoglein-2 (DSG2) is overexpressed in ~ 20% of bone marrow biopsies from newly diagnosed MM patients. Importantly, DSG2 expression was strongly predictive of poor clinical outcome, with patients expressing DSG2 above the 70th percentile exhibiting an almost 3-fold increased risk of death. As a prognostic factor, DSG2 is independent of genetic subtype as well as the routinely measured biomarkers of MM activity (e.g. paraprotein). Functional studies revealed a nonredundant role for DSG2 in adhesion of MM PC to endothelial cells. Together, our studies suggest DSG2 to be a potential cell surface biomarker that can be readily detected by flow cytometry to rapidly predict disease trajectory at the time of diagnosis.


A new comprehensive grading for giant pituitary adenomas: SLAP grading.
AimGiant pituitary adenomas are difficult to resect due to multicompartmental extension. We developed a new grading system for giant pituitary adenomas (GPAs) considering possible extension in superior, lateral, anterior, and posterior (SLAP) directions. We also related the degree of resection to the SLAP grading.MethodsA review of case files and radiological images of patients with the GPAs defined as pituitary adenomas with a size of more than 4 cm in any dimension was done. The extent of the tumour was noted and scored as per the SLAP system. The maximum total score is 10 and represents a large tumour with maximum extensions in all directions. The subtotal resection (STR) was defined as a residual tumour volume of more than 10%. The association between individual and total score on the degree of resection was determined.ResultsA total of 103 cases of GPAs were analyzed. All patients had a suprasellar (S) extension. The lateral (L) extension was seen in 97.3% of cases. The anterior (A) extension was seen in 28 (27.2%) cases. The posterior (P) extension was seen in 45 (43.7%). Forty-eight (46.6%) had a total score of 5 or more. The STR was achieved in 64 (62.2%) cases. On regression analysis, a total score of ≥5 was associated with odds of 5.02 (1.69-14.93), p-value 0.004 for STR.ConclusionThe SLAP grading is a comprehensive grading system that can be applied easily to the GPAs and gives a complete picture of the extension of the tumour.


Autoregulatory control of thyrotropin in rabbits.
Studies were designed to determine whether an autoregulation system exists for TSH in the rabbit. For this purpose, a species-specific RIA for rabbit TSH that does not cross-react with human (h) TSH was developed. Hypothyroid animals were studied at varying time periods up to 3 months after either surgical thyroidectomy or propylthiouracil (PTU) treatment. Highly purified hTSH was injected iv at doses of 0 (saline control), 0.1, 0.3, 1,3, and 10 micrograms into unanesthetized rabbits bearing chronically implanted Silastic catheters. Blood samples were obtained at -30, 0, 10, 20, 30, 60, 120, 180, 240, and 300 min and 24 h. Doses between 0.3 and 10 micrograms hTSH produced a prompt fall (10 min) in rabbit TSH in hypothyroid rabbits studied 8-21 days after thyroidectomy. The minimum dose of hTSH that significantly suppressed rabbit TSH was 0.3 micrograms. This dose produced a peak value of hTSH in rabbit serum of 1.3 +/- 0.1 (+/- SEM) ng/ml 10 min after injection, which translates into a bioassay potency of 2.0 microU/ml (close to the physiological level in humans). A dose-response relationship existed between the hTSH dose injected and the duration and magnitude of suppression of rabbit TSH. This response to TSH was specific; 10 micrograms hTSH produced no change in endogenous rabbit serum LH and, conversely, 10 IU hLH produced no change in rabbit serum TSH. In contrast to these striking effects in acute hypothyroid animals, hTSH produced no detectable suppression of rabbit TSH in animals that were hypothyroid for 2-3 months. The sensitivity of the autoregulatory system to the suppressive effects of exogenous hTSH decreased with increasing duration of hypothyroidism; a time-response relationship existed. We conclude that: 1) a sensitive and specific autoregulatory control system for TSH exists in the rabbit; and 2) as the duration of hypothyroidism increases, the sensitivity of the autoregulatory system to the suppressive effects of endogenous TSH changes.


Improving pose estimation accuracy for large hole shaft structure assembly based on super-resolution.
Image resolution is crucial to visual measurement accuracy, but on the one hand, the cost of increasing the resolution of the acquisition device is prohibitive, and on the other hand, the resolution of the image inevitably decreases when photographing objects at a distance, which is particularly common in the assembly of large hole shaft structures for pose measurement. In this study, a deep learning-based method for super-resolution of large hole shaft images is proposed, including a super-resolution dataset for hole shaft images and a new deep learning super-resolution network structure, which is designed to enhance the perception of edge information in images through the core structure and improve efficiency while improving the effect of image super-resolution. A series of experiments have proven that the method is highly accurate and efficient and can be applied to the automatic assembly of large hole shaft structures.


The expression of the 'pre-menstrual syndrome' in measures of mood and sustained attention.
Twenty-eight women performed two demanding sustained attention tasks in the premenstrual and intermenstrual phases of the menstrual cycle. Mood was assessed before and after performance. No effects of phase were found on perceptual sensitivity and response criterion, but response time on the less demanding of the two tasks was slower in the premenstrual phase. There were no effects of phase on pre-task mood, but following performance, premenstrual women were lower in energy and in pleasantness of mood. Moods varied with phase irrespective of usage of the contraceptive pill, but effects on response time were stronger in non-pill users. Performance data suggest that speed of visual discrimination varies with the cycle, but this finding is of little practical significance. The mood data suggest that the affective correlates of the cycle vary with situational stress, and, in the workplace, it may be desirable to reduce stress and workload during the premenstrual phase.


Spontaneous resolution of obstructive valvular tumors in infants.
Myxomas, the most common cardiac tumor in adults, occur in the atria and are prone to embolization. Obstructive valvular tumors in infants occur in pulmonic and aortic valves and generally have a more benign course. We conducted a review of our experience in infants with tumors obstructing the right or left ventricular outflow tract, originating from pulmonic or aortic valve tissue. Tissue diagnosis was available from only the index case; 4 additional infants survived with spontaneous regression, and only echocardiographic characterizations were available. Five cases were found with obstructing valvular tumors. In the index case, the obstruction resulted in heart failure, required surgical extirpation, and revealed histology diagnostic of a myxoma. In the subsequent 4 infants with conditions diagnosed with echocardiography, the appearance was suggestive of myxomas (small, compact, ovoid, with no fronds and no embolization). All 4 cases remained mildly to moderately obstructive and then showed spontaneous regression during a period of months to years. None of our cases deteriorated clinically, except the first, and were therefore different from other tumors, such as adult atrial myxomas, papillary fibroelastomas, fibromas, and rhabdomyomas. Only the latter are known to spontaneously regress in infancy. The prevalence of valvular tumors in infants may have previously been underestimated, given the absence of symptoms in 4 of our cases and the spontaneous regression of the tumor. An alternate diagnosis for these 4 cases could be a tissue "myxomatous rest" as opposed to a neoplastic myxoma. In either case, surgical intervention may not be necessary.


DEVELOPING RADIATION RESISTANT THERMAL NEUTRON DETECTORS FOR THE E_LIBANS PROJECT: PRELIMINARY RESULTS.
Radiation-resistant, gamma-insensitive, active thermal neutron detectors were developed to monitor the thermal neutron cavity of the E_LIBANS project. Silicon and silicon carbide semiconductors, plus vented air ion chambers, were chosen for this purpose. This communication describes the performance of these detectors, owing on the results of dedicated measurement campaigns.


Primary osteosarcoma of breast.
Primary osteosarcoma of breast is rare. The authors present a case of a 51-year-old female who was admitted with a large necrotising tumour involving the right breast. CT scan confirmed chest wall invasion along with a solitary lung metastasis. She underwent a primary mastectomy with chest wall reconstruction. Unfortunately 3 months later she developed local recurrence.


Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL).
Adult T cell leukemia/lymphoma (ATLL) is one of the peripheral T cell malignant neoplasms strongly associated with human T cell leukemia virus type-I (HTLV-I). Although the viral transactivating protein Tax has been proposed to play a critical role in leukemogeneis as shown by its transforming activity in various experimental systems, additional cellular events are required for the development of ATLL. One of the genetic events in ATLL is inactivation of tumor suppressor genes. Among many candidates for tumor suppressor genes, the main genetic events have been reported to center around the cyclin-dependent kinase inhibitors ((CDKIs) p15INK4A, p16INK4B, p18INK4C, p19INK4D, p21WAF1, p27KIP1, and p57KIP2), p53 and Rb genes; all of them play a major regulatory role during G1 to S transition in the cell cycle. Acute/lymphomatous ATLL has frequent alterations of p15 (20%) and p16 (28-67%), while chronic/smoldering ATLL has fewer abnormalities of p15 (0-13%) and p16 (5-26%). Most of these changes are deletion of the genes; fewer samples have mutations. ATLL patients with deleted p15 and/or p16 genes have significantly shorter survival than those individuals with both genes preserved. Although genetic alterations of p18, p19, p21, p27 have rarely been reported, inactivation of these genes may contribute to the development of ATLL because low expression levels of these genes seem to mark ATLL. The p53 gene is mutated in 10-50% of acute/lymphomatous ATLL. Functional impairment of the p53 protein, even if the gene has wild-type sequences, has been suggested in HTLV-I infected cells. Each of these genetic events are mainly found in acute/lymphomatous ATLL, suggesting that alterations of these genes may be associated with transformation to an aggressive phenotype. The Rb tumor suppressor gene is infrequently structurally altered, but one half of ATLL cases have lost expression of this key protein. Notably, alterations of one of the CDKIs, p53 and Rb genes appear to obviate the need for inactivation of other genes in the same pathway. A novel tumor suppressor gene on chromosome 6q may also have a critical role in the pathogenesis of ATLL. Taken together, tumor suppressor genes are frequently altered in acute/lymphomatous ATLL and their alteration is probably the driving force fueling the transition from chronic/smoldering to acute/lymphomatous ATLL.


Changes in dynamic crossover with temperature and pressure in glass-forming diethyl phthalate.
Dielectric relaxation measurements have been used to study the crossover in dynamics with temperature and pressure, onset of breakdown of the Debye-Stokes-Einstein law, and the relation between the alpha and the beta relaxations in diethyl phthalate. The measurements made over 10 decades in frequency and a broad range of temperature and pressure enable the dc conductivity and the alpha- and the beta-relaxations to be studied altogether. The isobaric data show that the alpha-relaxation time tau(alpha) has temperature dependence that crosses over from one Vogel-Fulcher-Tammann-Hesse form to another at T(B) approximately 227 K and tau(alpha) approximately 10(-2) s. The dc conductivity sigma exhibits similar crossover at the same T(B). At temperatures above T(B), tau(alpha) and sigma have the same temperature dependence, but below T(B) they become different and the Debye-Stokes-Einstein law breaks down. The breadth of the alpha relaxation is nearly constant for T<T(B), but decreases with increasing temperature for T>T(B). The time dependence of tau(beta) is Arrhenius, which when extrapolated to higher temperatures intersects tau(alpha) at T(beta) nearly coincident with T(B). Isothermal measurements at various applied pressures when compared with isobaric data show that the shape of the alpha-relaxation depends only on tau(alpha), and not on the T and P combinations. At a constant temperature, while tau(alpha) increases rapidly with pressure, the beta-relaxation time tau(beta) is insensitive to applied pressure. This behavior is exactly the same as found in 1,1(')-bis (p-methoxyphenyl) cyclohexane. The findings are discussed in the framework of the coupling model.


Prognostic factors that determine the long-term survival of patients with unresectable metastatic melanoma.
This retrospective analysis aimed to identify the prognostic factors that influenced long-term survival of patients with metastatic melanoma. The medical records for 616 chemo-naive patients who were treated with systemic therapy on eight phase II/III clinical trials were reviewed. Clinical characteristics, disease stage, metastatic sites, baseline serum albumin, LDH, and response to treatment were compared between the treatment groups and significant prognostic factors were identified. Cox proportional-hazards regression analysis identified treatment with biochemotherapy, younger age, normal baseline serum albumin and LDH levels, ECOG P.S. < 2 and absence of visceral metastasis as favorable prognostic factors for long-term survival.


Purification of alkaline phosphatase from the alimentary canal of Schistocerca gregaria (Forskal).
A method for the purification of alkaline phosphatase is described and some properties of the purified product determined. A 362-fold purification was obtained and enzyme is homogeneous as judged by SDS-gel electrophoresis. The molecular weight is 5.3 X 10(4) approximately, by disc-electrophoresis and also according to gel filtration and sucrose density-gradient.


Endocrine disturbances related to the use of lithium.
Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment.


Role of the renin-angiotensin system in the adaptation of aldosterone biosynthesis to sodium restriction in the rat.
The purpose of the present study was to evaluate the role of the renin-angiotensin system in the secretion of aldosterone during restriction of dietary sodium intake. Rats were kept on control or low-sodium diet for one week. On the 7th morning of diet osmotic minipumps filled with the angiotensin converting enzyme inhibitor (CEI) SQ 20,881, or empty pumps, were implanted subcutaneously (sc). The rats were sacrificed 23 h later. Peripheral blood was analyzed for hormones and electrolytes. Adrenal capsular tissue (z. glomerulosa) was incubated for the determination of the conversion of [3H]corticosterone to [3H]aldosterone. Sodium depletion had no effect on plasma sodium, but it increased potassium concentration. Infusion of CEI had no significant effect on plasma electrolytes. Plasma renin activity was increased both by sodium depletion and CEI. The mean serum aldosterone level was twelve times higher in sodium depleted animals than in controls. Aldosterone level was reduced by about 60 per cent in CEI-infused animals both on control and low-sodium diet. The conversion of corticosterone to aldosterone was significantly stimulated by sodium deprivation. This effect was also inhibited by the CEI SQ 20,881.


Why openness with health inspectors pays.
The effect of the quality of information obtained by Standards Monitoring Teams on the compliance of 410 Australian nursing homes with Commonwealth regulatory standards is explored. We find that information matters. Lack of openness is a hallmark of a poor quality facility, openness of a high quality facility. Secondly, open flow of information becomes a resource that does enable the regulatory process to improve the quality of care. From an industry perspective, therefore, openness pays because it 1. works against being marked off by an inspection team as a problem facility that is covering up; and 2. allows the facility to improve the quality of the service it delivers to the consumer.


Calcium phosphatase calcineurin influences tau metabolism.
Alzheimer's disease (AD) is characterized by neuronal loss and the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. Cerebrospinal fluid (CSF) levels of β-amyloid and tau/phospho-tau 181 (ptau 181) are also associated with AD. We have previously demonstrated that a single nucleotide polymorphism in calcineurin is associated with CSF ptau 181 levels and AD progression. In this study, we demonstrate that calcineurin protein levels are inversely correlated with dementia severity and Braak tangle stage in AD brains, and calcineurin activity is globally reduced in AD brains. We then sought to model the observed changes in CSF tau by measuring extracellular tau in cultured cells. SH-SY5Y cells treated with calcineurin inhibitors produced reduced calcineurin activity and a corresponding increase in extracellular ptau 181. These findings are consistent with our observations in AD patients, who have elevated CSF ptau 181 and reduced calcineurin activity in brain extracts. Thus, we have identified a gene that contributes to AD pathology and has functional consequences on tau metabolism in cultured cells.


Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small Animals at 3T and 7T, Respectively.
The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field. In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7 T and 3 T, respectively to perform whole-body and musculoskeletal imaging. "Sum-Of-Square" reconstruction was performed and combined or not with parallel imaging. The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body small animal 3D imaging was performed at 7 T and enabled visualization of small structures within adipose tissue like lymph nodes. In parallel, this method allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3 T. The combination with parallel imaging allowed the acquisition of knee images with ~500 μm resolution images in less than 2 min. In addition, ankles, full head coverage and legs of volunteers were imaged, demonstrating the possible application of the method also for large FOV. In conclusion, this robust method can be applied in small animals and humans at high magnetic fields. The high SNR and tissue contrast obtained in short acquisition times allows to prescribe bSSFP sequence for several preclinical and clinical applications.


Vasopressin-induced facilitation of adrenergic responses in the rat mesenteric artery is V1-receptor dependent.
1. The present study was designed to analyse the possible involvement of V1- and V2-receptors in vasopressin (AVP)-induced facilitation of the sympathetic nervous system. Furthermore, we aimed to determine whether the site of facilitation by AVP is located pre- or postsynaptically. 2. Electrical field stimulation (EFS) was applied on the rat mesteric artery to activate the sympathetic nervous system. In addition, we evaluated the direct vascular effects of AVP. The postsynaptic effect of AVP on the sympathetic nervous system was investigated by exposing the vessels to exogenous noradrenaline. These experiments were performed in the absence or presence of selective V1 and V2 receptor antagonists SR 49059 and SR 121463, respectively. Desmopressin was applied as a selective V2 agonist. 3. The direct vasoconstrictor effect of AVP was antagonized by SR 49059 and not by SR 121463. Desmopressin neither showed any direct vasoconstrictor effect nor produced vasodilatation after a precontraction induced by noradrenaline (10 microM). The EFS-induced rise in vascular tone could be increased by a sub-pressor concentration of AVP. This fascilitation could be antagonized by SR 49059, but not by SR 121463. Desmopressin did not influence the increase in vascular tone during EFS. Vasoconstriction induced by exogenous noradrenaline could be facilitated by a sub-pressor concentration of AVP and this selective postsynaptic effect could be antagonized by V1-receptor blockade. 4. In conclusion, the AVP-induced facilitation of the sympathetic nervous system is completely V1-receptor dependent and at least partly postsynaptically mediated.


17beta-estradiol inhibition of NADPH oxidase expression in human endothelial cells.
We investigated the hypothesis that the antiatherosclerotic effect of 17beta-estradiol (E2) is due to a shift in the nitric oxide (NO)/superoxide (O2-) balance in the vessel wall, thereby increasing the bioavailability of NO. In human umbilical vein cultured endothelial cells, E2 (1-100 nmol/l), but not 17alpha-estradiol, caused a time- and concentration-dependent decrease in expression of the NADPH oxidase subunit gp91phox (up to 60% inhibition at both the mRNA and protein level). This effect was prevented by coincubation with the estrogen receptor antagonists tamoxifen and ICI 182,780 (1 micromol/l each). Within the same concentration range, E2 also up-regulated endothelial nitric oxide synthase expression ( approximately twofold). Moreover, preincubation of the cells with E2 or a gp91phox antisense oligonucleotide significantly decreased their capacity to generate O2- on phorbol ester stimulation (i.e., assembly of the active NADPH oxidase complex). Blockade of NO synthase activity, on the other hand, had no effect on phorbol ester-stimulated O2- formation. In addition, E2 (100 nmol/l) inhibited the increase in adhesion molecule and chemokine expression in cells exposed to cyclic strain. Cyclic strain enhanced endothelial O2- formation, thereby offsetting the inhibitory effect of NO on the expression of these gene products. E2 thus seems to act as an antioxidant at the genomic level which by improving the NO/O2- balance normalizes expression of proatherosclerotic gene products in endothelial cells.


The diagnosis, classification, and treatment of sarcoma in this era of artificial intelligence and immunotherapy.
Soft-tissue sarcomas (STS) represent a group of rare and heterogeneous tumors associated with several challenges, including incorrect or late diagnosis, the lack of clinical expertise, and limited therapeutic options. Digital pathology and radiomics represent transformative technologies that appear promising for improving the accuracy of cancer diagnosis, characterization and monitoring. Herein, we review the potential role of the application of digital pathology and radiomics in managing patients with STS. We have particularly described the main results and the limits of the studies using radiomics to refine diagnosis or predict the outcome of patients with soft-tissue sarcomas. We also discussed the current limitation of implementing radiomics in routine settings. Standard management approaches for STS have not improved since the early 1970s. Immunotherapy has revolutionized cancer treatment; nonetheless, immuno-oncology agents have not yet been approved for patients with STS. However, several lines of evidence indicate that immunotherapy may represent an efficient therapeutic strategy for this group of diseases. Thus, we emphasized the remarkable potential of immunotherapy in sarcoma treatment by focusing on recent data regarding the immune landscape of these tumors. We have particularly emphasized the fact that the development of immunotherapy for sarcomas is not an aspect of histology (except for alveolar soft-part sarcoma) but rather that of the tumor microenvironment. Future studies investigating immunotherapy strategies in sarcomas should incorporate at least the presence of tertiary lymphoid structures as a stratification factor in their design, besides including a strong translational program that will allow for a better understanding of the determinants involved in sensitivity and treatment resistance to immune-oncology agents.


Effects of different organic farming methods on the concentration of phenolic compounds in sea buckthorn leaves.
The effects of different cultivation methods on the amount of phenolic compounds in leaves of 1-year-old seedlings of two Finnish sea buckthorn (Hippophae rhamnoides L. ssp. rhamnoides) cultivars 'Terhi' and 'Tytti' were studied in a field experiment established at coastal area in Merikarvia, western Finland. The cultivation methods included different fertilizers (suitable for organic cultivation), mulches (organic and plastic), and land contours (flat vs low hill surface). Two experiments were conducted. The first allowed the estimation of the effects of cultivar, fertilizer, surface contour, and all their interactions, while the other allowed the estimation of the effects of mulches, land contours, and their interactions for the cultivar 'Tytti'. Eleven different hydrolyzable tannins, pentagalloylglucose, and 14 other phenolic compounds were detected by chemical analysis with high-performance liquid chromatography (HPLC). The amount of phenolic compounds varied between different land contours and mulches. The concentrations of gallic acid, pentagalloylglucose, quercetin-3-rhamnoside, monocoumaroyl astragalin A, total hydrolyzable tannins, and condensed tannins were significantly higher on the flat surface than on the low hill surface. The plastic mulch decreased the concentration of gallic acid, hydrolyzable tannins, and condensed tannins compared to the other mulches used. These results suggest ways to cultivate sea buckthorn to produce large amounts of valuable chemicals, especially tannins in the leaves.


The Preservation of Cognition 1 Year After Carotid Endarterectomy in Patients With Prior Cognitive Decline.
Vascular cognitive decline is critically important in the course of atherosclerosis and stroke. To explore the hypothesis that carotid endarterectomy (CEA) by removing an unstable plaque may slow the course of vascular cognitive decline in both symptomatic and asymptomatic patients. Patients with clinically significant (>60%) carotid stenosis were studied preop and 1 yr post-CEA for clinical symptoms, vascular cognitive decline, instability of carotid plaque-presence of microemboli, brain white matter changes, and medical risk factors. Forty-six percent were classically symptomatic. All patients showed vascular cognitive decline at presentation which correlated with degree of plaque instability. Significant white matter hyperintensity changes (48.7%) and cerebral emboli (25%) were also seen at baseline in both classically symptomatic and asymptomatic. One year after CEA, both groups showed no decline in cognitive function and significant improvement in 2 tests (P = .028 and P = .013). Brain white matter hyperintensities were unchanged. Microemboli were reduced but remained present (17.86%). Improvement was predicted by the presence of hypertension (P = .001), or less advanced cognitive decline preoperatively (P = .009). This study demonstrates the importance of vascular cognitive decline in atherosclerotic disease. This is a function of the degree of instability of the atherosclerotic plaque more than the presence of stroke symptoms. It further suggests that atherosclerotic vascular cognitive decline need not be inevitable, and may be modified by treating hypertension and removal of the unstable plaque. This highlights the need for continued research on the cognitive effects of cerebrovascular disease and the synergistic benefits of intensive medical and surgical therapy.


Isoflurane-induced preconditioning is attenuated by diabetes.
Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K(+) channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 +/- 3% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 +/- 3%; n = 8) but blocked the protective effects of 0.32% (27 +/- 2%; n = 7) and not 0.64% isoflurane (18 +/- 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.


Paclitaxel Nanoparticles Induce Apoptosis and Regulate TXR1, CYP3A4 and CYP2C8 in Breast Cancer and Hepatoma Cells.
Although the anticancer potentials of water-insoluble drugs are improved by nanoformulation, other intervening factors may contribute in the drug efficacy. This work was designated to explore the effect of paclitaxel-loaded Poly(Lactic-co-Glycolic Acid) (PLGA) nanoparticles on the viability of cancer cells, the expression of Taxol Resistance gene I (TXR1) and paclitaxel metabolizing genes. Paclitaxel loaded PLGA Nanoparticles (PTX-NPs) were prepared, physically characterized and used in the treatment of breast adenocarcinoma cells (MCF-7) and hepatoma cells (HepG2). Cells viability and apoptosis were investigated. In parallel, RNA was isolated, reverse transcribed and used to monitor the expression levels of TXR1, CYP 3A4 and CYP2C8 genes. PTX-NPs were characterized by transmission electron microscopy to be of a nano-size sphere-like shape. FTIR analysis revealed good coupling between PTX and PLGA. The encapsulation efficiency was 99% and the drug release demonstrated a progressive releasing phase followed by slower and sustained releasing phases. Although HepG2 cells demonstrated more resistance to PTX than MCF-7 cells, both cell types were more responsive to PTX-NPS compared to PTX. The IC50 values decreased from 19.3 to 6.7 in breast cancer cells and from 42.5 to 13.1μg/ml in hepatoma cells. The apoptosis was the key mechanism in both cells, where at least 44% of cells underwent apoptosis. The expression of TXR1 decreased when either cells were treated with PTX-NPs, respectively, meanwhile the expressions of CYP3A4 and CYP2C8 were increased. Taken together, this in vitro study reports the associations between the enhanced responsiveness of MCF-7 and HepG2 cells to PLGA-loaded paclitaxel nanoparticles and the accompanying decrease in the cells resistance to the PTX and its enhanced metabolism.


Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia.
Regular adolescent cannabis use predicts a range of later drug use and psychosocial problems. Little is known about whether occasional cannabis use carries similar risks. To examine associations between occasional cannabis use during adolescence and psychosocial and drug use outcomes in young adulthood; and modification of these associations according to the trajectory of cannabis use between adolescence and age 20 years, and other potential risk factors. A 10-year eight-wave cohort study of a representative sample of 1943 secondary school students followed from 14.9 years to 24 years. Occasional adolescent cannabis users who continued occasional use into early adulthood had higher risks of later alcohol and tobacco dependence and illicit drug use, as well as being less likely to complete a post-secondary qualification than non-users. Those using cannabis at least weekly either during adolescence or at age 20 were at highest risk of drug use problems in young adulthood. Adjustment for smoking in adolescence reduced the association with later educational achievement, but associations with drug use problems remained. Occasional adolescent cannabis use predicts later drug use and educational problems. Partial mediation by tobacco use raises a possibility that differential peer affiliation may play a role.


How Cells Fold the Cerebral Cortex.
Folding of the cerebral cortex is as highly intriguing as poorly understood. At first sight, this may appear as simple tissue crumpling inside an excessively small cranium, but the process is clearly much more complex and developmentally predetermined. Whereas theoretical modeling supports a critical role for biomechanics, experimental evidence demonstrates the fundamental role of specific progenitor cell types, cellular processes, and genetic programs on cortical folding.Dual Perspectives Companion Paper: How Forces Fold the Cerebral Cortex, by Christopher D. Kroenke and Philip V. Bayly.


Cytologic analysis in fine-needle aspiration biopsy: smears vs cell blocks.
Imaging-directed fine-needle aspiration biopsy can be performed with or without immediate cytologic assessment (smears). We compared the results obtained immediately from cytologic smears with the results of cell-block analysis. We wished to determine the frequency of false-negative findings on cytologic smears in patients subsequently found to have malignant tumors by cell-block analysis. We retrospectively reviewed the records for 100 consecutive biopsies performed between January 1986 and August 1987. In each case, specimens were obtained from both a 22-gauge and a 20-gauge notched needle placed in tandem. The study group consisted of 84 patients who had results of analyses of both cytologic smears and cell blocks available for review and who had clinical or surgical correlation. Sixty-four (76%) of the 84 biopsies yielded malignant tumor cells, 11 yielded evidence of a benign process, and nine were not diagnostic. Malignant tumor cells were seen on the cytologic smears in 55 (86%) of the 64 patients who had malignant tumors; in the other nine patients, the malignant tumors were indicated by the cell-block analysis only. Within the group of benign disorders, in only one case (9%) was the cell block diagnostic when the cytologic smear was not. Operators performing fine-needle aspiration biopsy should be aware of the limitations of immediate cytologic evaluation. Cell-block analysis of the aspirate remaining after the smears are made can be expected to increase the diagnostic accuracy in up to 14% of patients.


Aberrant DNA methylation imprints in aborted bovine clones.
Genomic imprinting plays a very important role during development and its abnormality may heavily undermine the developmental potential of bovine embryos. Because of limited resources of the cow genome, bovine genomic imprinting, both in normal development and in somatic cell nuclear transfer (SCNT) cloning, is not well documented. DNA methylation is thought to be a major factor for the establishment of genomic imprinting. In our study, we determined the methylation status of differential methylated regions (DMRs) of four imprinted genes in four spontaneously aborted SCNT-cloned fetuses (AF). Firstly, abnormal methylation imprints were observed in each individual to different extents. In particular, Peg3 and MAOA were either seriously demethylated or showed aberrant methylation patterns in four aborted clones we tested, but Xist and Peg10 exhibited relatively better maintained methylation status in AF1 and AF4. Secondly, two aborted fetuses, AF2 and AF3 exhibited severe aberrant methylation imprints of four imprinted genes. Finally, MAOA showed strong heterogeneous methylation patterns of its DMR in normal somatic adult tissue, but largely variable methylation levels and relatively homogeneous methylation patterns in aborted cloned fetuses. Our data indicate that the aborted cloned fetuses exhibited abnormal methylation imprints, to different extent, in aborted clones, which partially account for the higher abortion and developmental abnormalities during bovine cloning.


Nurse-led diabetic retinopathy screening: a pilot study to evaluate a new approach to vision care for Canadian Aboriginal peoples.
Diabetic retinopathy is the most common cause of new cases of blindness and is pandemic among Aboriginal people around the world. To reduce health inequities, accessible vision screening among these high-risk populations is essential. To assess cardio-metabolic co-morbidities associated with type 2 diabetes and the use of a portable fundus camera as a novel approach for convenient, earlier and more accessible vision screening for Aboriginal peoples living with type 2 diabetes in northern and remote Canadian communities. This quantitative pilot study screened participants diagnosed with type 2 diabetes for commonly associated cardio-metabolic co-morbidities using anthropometrical measurements, blood pressure and a A1c (HbA1c) blood glucose test, followed by vision exams conducted first by a trained nurse and then by an ophthalmologist to screen for signs of retinopathy using fundus photography. Large numbers of the participants presented with overweight/obese (84.8%), pre-hypertension/hypertension (69.7%) and an elevated A1C (78.8%). Inter-rater reliability demonstrated substantial agreement between vision exam judgements made by the nurse and ophthalmologist (k = .67). Nurse-led vision screening in remote or northern communities can improve the standard of care by extending access to health services, lowering the costs to families by reducing travel expenses and preventing vision loss in a family member.


Cytochrome P4501A1 and microsomal epoxide hydrolase gene polymorphisms: gene-environment interaction and risk of prostate cancer.
The role of low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear. Most procarcinogens require metabolic activation by CYP4501A1, whereas microsomal epoxide hydrolase (mEH) is involved in the detoxification. In our case-control study, we assessed whether CYP1A1 and mEH susceptibility genotypes, tobacco use, and age factors contribute to PCa risk. One hundred thirty patients with PCa and 140 control subjects were analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method from genomic DNA samples. Binary logistic regression model was used for assessing differences in genotype prevalence and their association between patient and the control group. T/C polymorphism of CYP1A1 gene revealed significant association with the tobacco users (p < 0.005) for PCa risk. Our results demonstrated significant association with exon 3 variant genotypes of the mEH alone or in combination with tobacco users (p < 0.005), whereas in exon 4 genotypes, no association was observed. Haplotype analysis projected significant associations with very slow haplotypes of mEH gene (OR = 2.48, 95% CI = 1.41-4.38, p = 0.002). In conclusion, our study demonstrated that exon 3 of mEH and CYP1A1 T/C gene polymorphism are predisposing risk factors for susceptibility of sporadic PCa in northern India. It also suggests that a combination of smoking plays a significant role in modified PCa risk on the study population, which means that smokers carrying susceptible genotypes may be subjected to higher risk than those carrying nonsusceptible genotypes.


Fiber-optic sleep endoscopy in children with persistent obstructive sleep apnea: inter-observer correlation and comparison with awake endoscopy.
Evaluate the inter-observer correlation of sleep endoscopy findings in children with persistent obstructive sleep apnea (OSA) with awake office fiber-optic endoscopy. retrospective case series; blinded review. tertiary care children's hospital. Children with persistent obstructive sleep apnea. Both awake and drug induced sleep endoscopy were performed. Endoscopy video recordings were mixed at random on a DVD. Two pediatric otolaryngologists and two pediatric pulmonologists independently scored each recording using an upper airway endoscopy scoring survey. reviewers scored the following parameters: each structure's contribution (nose, nasopharynx, lateral pharyngeal walls, tongue base, supraglottis) to the obstruction, the main site in which the obstruction occurs, the severity of OSA (mild, moderate, severe), the level of confidence of endoscopy findings (poor, fair, good). When reviewing sleep endoscopy recordings for the upper airway obstruction site, the highest correlation among the four observers was found for the nasopharynx and the supraglottis (Kappa score: 0.6 and 0.5, respectively). Compared to awake endoscopy, sleep endoscopy demonstrated more cases of airway obstruction caused by collapse of lateral pharyngeal walls and base of tongue (McNemar test for symmetry, P value<0.05). Level of confidence among the four observers was higher in older children and lower in children with severe OSA. Sleep endoscopy is a consistently reliable tool for identifying the site of obstruction in children with persistent OSA. Though anesthetic induced sleep is not a perfect model for real sleep, the technique demonstrably guides further therapy better than awake endoscopy.


When is Early Antiretroviral Therapy Early Enough for HIV Remission?
Several strategies to reduce and control the HIV reservoir are being evaluating to achieve the great challenge of HIV remission or functional cure. Some of these are based on immune and gene therapy, or in the use of agents with latency reversing properties. Moreover, acute HIV infection and the impact of early antiretroviral treatment (ART) initiation is another key issue of current research. It has been demonstrated that ART initiation during acute HIV infection minimizes the establishment of the latent HIV reservoir. Therefore, early ART initiation might delay viral rebound following treatment interruption and might potentially induce a post-treatment controller state. In this regard, new interesting data were presented at CROI 2017, recently held in Seattle.


[Plasma-androgens following oral administration of testosterone. Influence of sex, age, and liver function (author's transl)].
The influence of sex, age, and liver function on the androgenmetabolizing capacity of the liver was investigated. To that end, testosterone was administered orally to healthy men, women and prepubertal boys as well as to men with liver dysfunction. While normal men (n = 17) and men with fatty liver (n = 9) showed no rise in circulating plasma testosterone levels and only a slight increase in androstenedione, a steep increase in both steroids was observed in men with liver cirrhosis (n = 7). Unlike adult men, boys (n = 7) and women (n = 6) also showed elevated testosterone levels after oral administration of this steroid. It is concluded that the hepatic capacity to metabolize testosterone is influenced by sex, stage of development, and liver function. It seems possible that peripheral concentration of testosterone after its oral administration can serve as a clinical test for liver function.


Detection of diabetic foveal edema with biomicroscopy, fluorescein angiography and optical coherence tomography.
To describe different techniques for the detection of diabetic foveal edema. A retrospective review of the detection of diabetic foveal edema. Noncontact lens biomicroscopy is relatively insensitive in mild foveal thickening apparent on optical coherence tomography. Optical coherence tomography measurements can detect early retinal damage in diabetic retinopathy patients.


[Etiology of the epidemic outbreak of community-acquired pneumonia in children in St. Petersburg].
In September-December 1998 the epidemic rise of outhospital pneumonia (EP) among children was observed in St. Petersburg, which led to a twofold increase in morbidity rate this year. The study of the etiology of EP during the period of 1998-2001 confirmed the prime role of Streptococcus pneumoniae (74.5%) and, for the first time in Russia, revealed the epidemic outbreak of acute chlamydiosis (Chlamydia pneumoniae), diagnosed in 67.3% of children, the maximum occurrence (87.5%) in 1998 with only 19% of the patients having the disease in the form of monoinfection. The prevalence of S. pneumoniae and C. pneumoniae in the etiology of EP and more severe course of mixed infection suggested that these infective agents played a leading role in the epidemic outbreak of acute respiratory infections in St. Petersburg.


The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid cancer.
We have previously shown that miR-146a, a NF-κB-regulated microRNA, is strongly expressed in human specimens and cell lines derived from anaplastic thyroid carcinomas (ATC) where it mediates some of the NF-κB pro-tumorigenic functions. By using a bioinformatic analysis, we identified the chemokine scavenger receptor D6/ ACKR2 as a target of miR146a in human ATC. We found that the expression of D6/ ACKR2 was up-regulated in miR-146a-null ATC cell lines and that the 3' UTR of D6/ ACKR2 mRNA was able to inhibit its expression in parental, but not in miR-146a-null ATC cells. Since human specimens from primary ATC showed a low expression of D6/ ACKR2 compared to normal thyroid tissues, we analyzed the effects of D6/ACKR2 over-expression in ATC cells. Different chemokines added to the conditioned medium of D6/ACKR2 over-expressing ATC cells partially failed to drive in vitro monocyte migration, and tumors derived from the injection of the same cells in nude mice showed a decreased number of infiltrating macrophages. Taken together, these results indicate that ATC cells down-regulate D6/ACKR2 expression through miR-146a activity to sustain leukocyte trafficking inside tumor microenvironment and shed light on a novel mechanism by which NF-κB indirectly inhibits the expression and the function of anti-tumorigenic gene in thyroid cancer.


Generalization of helicoidal beams for short pulses.
A generalization to the transient regime is developed for waves with a phase singularity of the screw type. These singular waves are commonly called vortices for all kind of waves as, for instance, optical vortex or acoustical vortex. We generalize the definition of vortices to get an azimuthal velocity invariant for all the frequency components contained in the broad spectrum of a short pulse. This generalization leads to a modification of the orbital angular momentum definition. Another generalization is introduced by considering helicoidal waves with a finite number of turns. We demonstrate that, in this last case, the topological charge is no longer an integer. This provides a physical interpretation to vortices of fractional charge that are involved here to take into account the diffraction occurring at both tips of the now finite helical wave front. We show that shortening the pulse implies an angular localization of the wave energy and, as a consequence, a spreading of the angular momentum amplitude due to the uncertainty principle.


The Cognitive Information Effect of Televised News.
The purpose of this review is to summarize the key findings which prove that the biased perceptions of viewers may provide an inaccurate image of the informational validity of televised news. The news may generate distorted recollections of what occurred in particular reported events if displayed routines influence viewers not to pay attention to the essential features of a narrative. Elaborating on Fiske and Hartley (2010), Zelizer (2010), and Gunter (2015), we indicate that the character of the news setting has altered and individuals' news consumption routines have changed in adapting to media advancements. The news may be undergone at various psychological stages by news publics. Televised news may transmit information undeviatingly to publics that may (not) be committed successfully to memory. Our paper shows that individuals' skills to handle information that is displayed in a linguistic configuration are influenced by their abilities in the utilization of certain symbol systems that are employed to represent notions and meanings. Televised news may shape what individuals grasp, influence their perceptions, convictions, and views regarding prevailing events and matters, and transmit knowledge and interpretation. If news stories can be jotted down in a linguistic style that sidesteps making needless processing demands and captivate news users by facilitating them to make connections with former knowledge, they may be more worthy of note and more edifying. We conclude that news narratives present a cognitive demanding task to individuals, displaying novel information regarding evolving events in a multifarious format. Broadcast news exhibits intricate contents, displaying configurations that employ excessively the cognitive abilities for information processing of viewers.


Shared transcription factors contribute to distinct cell fates.
Genome-wide transcription factor (TF) binding profiles differ dramatically between cell types. However, not much is known about the relationship between cell-type-specific binding patterns and gene expression. A recent study demonstrated how the same TFs can have functional roles when binding to largely non-overlapping genomic regions in hematopoietic progenitor and mast cells. Cell-type specific binding profiles of shared TFs are therefore not merely the consequence of opportunistic and functionally irrelevant binding to accessible chromatin, but instead have the potential to make meaningful contributions to cell-type specific transcriptional programs.


Porcine lung surfactant protein B gene (SFTPB): cDNA sequencing, chromosomal location, and expression studies.
The porcine surfactant protein B (SFTPB) is a single copy gene on chromosome 3. Three different cDNAs for the SFTPB have been isolated and sequenced. Nucleotide sequence comparison revealed six nonsynonymous single nucleotide polymorphisms (SNPs), four synonymous SNPs and an in-frame deletion of 69 bp in the region coding for the active protein. Northern analysis showed lung-specific expression of three different isoforms of the SFTPB transcript. The expression level for the SFTPB gene is low in 50 days-old fetus and it increases during lung development. Quantitative real-time polymerase chain reaction (qPCR) showed significant down regulation of the SFTPB in pigs with Actinobacillus pleuropneumoniae lung infection.


A vegetally localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation.
Pattern formation in early embryogenesis is guided by maternal, localized determinants and by inductive interactions between cells. In Xenopus eggs, localized molecules have been identified and some, such as Vg1 and Xwnt-11, can specify cell fates by functioning as inducers or patterning agents. We have used differential screening to identify new Xenopus genes that regulate mesodermal patterning, and we have isolated a new member of the T-box family of transcription factors. This gene, named Brat, is expressed maternally and its transcripts are localized to the vegetal hemisphere of the egg. During early embryonic cleavage, Brat mRNA becomes partitioned primarily within vegetal cells that are fated to form the endoderm. Zygotic expression of Brat begins at the onset of gastrulation within the presumptive mesoderm of the marginal zone. Consistent with its zygotic expression pattern, Brat induces, in a dose-dependent manner, a full spectrum of mesodermal genes that mark tissues across the dorsal-ventral axis, from the blood through the Spemann organizer. Brat also induces endoderm, consistent with its vegetal localization, making Brat a good candidate for a maternal determinant of the endoderm. We tested whether endogenous Brat is required for mesoderm formation by expressing a dominant-negative, transcriptional repressor form of Brat in embryos. This treatment inhibited mesoderm formation and severely disrupted normal development, thereby establishing that Brat plays a critical role in embryonic mesoderm formation and body patterning.


An oxygen cathode operating in a physiological solution.
We report the electroreduction of O(2) to water under physiological conditions (pH 7.4, 0.15 M NaCl, 37.5 degrees C) at a current density of 5 mA cm(-2) and at a potential only 0.18 V reducing versus that of the reversible O(2)/H(2)O electrode at pH 7.4. The immobilized electrocatalyst enabling the reduction is the electrostatic adduct of bilirubin oxidase from Myrothecium verrucaria, a polyanion at pH >4.1, and the polycationic redox copolymer of polyacrylamide and poly (N-vinylimidazole) complexed with [Os (4,4'-dichloro-2,2'-bipyridine)(2)Cl](+/2+), cross-linked on carbon cloth. The current density of the rotating electrodes was O(2) transport limited up to 8.8 mA cm(-2); their kinetic limit was reached at 9.1 mA cm(-2). The operational life of the electrodes depended on their angular velocity, which defined not only the current density but also the mechanical shear stress stripping the electrocatalyst. When the electrodes were rotated at 300 rpm and were poised at -256 mV versus the potential of the reversible O(2)/H(2)O electrode, their 2.4 mA cm(-2) initial current density decreased to 1.3 mA cm(-2) after 6 days of continuous operation at 37.5 degrees C.


Identification of a missense mutation in an adult-onset patient with glycogenosis type II expressing only one allele.
The lysosomal enzyme acid alpha glucosidase (GAA) or acid maltase is deficient in glycogen storage disease type II. We sought to determine the molecular basis for the disease in an adult-onset patient, unusual for very low enzyme activity similar to that seen with the infantile-onset form and with a previously reported defect in phosphorylation. We constructed cDNA and genomic DNA libraries from the patient's cell line (GM 1935) and determined the nucleotide sequence of the coding region. There were three base-pair substitutions in one allele (C1935 to A; G2446 to A and C2780 to T), all predicting amino acid changes (Asp-645 to Glu; Val-816 to Ile and Thr-927 to Ile). To determine which of the three base-pair substitutions resulted in loss of enzyme activity, we next utilized primer-directed mutagenesis and transient gene expression in an SV40-immortalized GAA-deficient fibroblast cell line. Only the construct containing the G2446 to A mutation (Val-816 to Ile) lost GAA enzyme activity, while the other two substitutions (including the Thr-927 to Ile change that predicts a loss of a potential site for N-linked glycosylation and mannose phosphorylation) each resulted in enzyme activity equal to the control. Analysis of RFLPs in genomic DNA, as well as sequence analysis for the three base-pair alterations, indicated that the patient was a genetic compound. We next digested PCR-amplified cDNA (reverse-transcribed from RNA) with Aat II to detect the base-pair 1935 substitution and found that virtually all of the mRNA was derived from the allele with the three base-pair substitutions.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimizing outcomes in pregnant women with epilepsy.
Women with epilepsy are more likely to have maternal and fetal complications during pregnancy. Risks can be minimized with preconception planning, careful obstetric care, and close postpartum follow-up.


Control of the average spacing between aligned gold nanoparticles by varying the FIB dose.
This work presents a new method to align gold nanoparticles (Au NPs), based on three well-known techniques: self-assembled monolayer (SAM) formation, focused ion beam (FIB) lithography, and organo-metallic chemical vapour deposition (OMCVD). Silicon substrates are coated with CH(3)-terminated silane SAMs as resists. A fine beam of Ga(+) ions, applying different doses, damages/removes these SAMs to correspondingly form a pattern containing sets of lines. Atomic force microscopy (AFM) and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) are used to study the SAM removal process. The FIB nano-lithographically patterned SAMs are re-filled with an SH-terminated silane SAM. An OMCVD process is carried out to grow Au NPs onto the SH-groups in the lines. The average spacing between the Au NPs is demonstrated to be controlled by varying the FIB dose. Scanning electron microscopy (SEM) image analysis indicates that the average spacing decreases exponentially with increasing the dose, up to a predefined threshold. In addition, the formation of OMCVD Au NPs spacing and its dose-dependence in the absence of the SH-terminated SAMs is studied.


Selective and sensitive fluorescence chemosensor for the hypochlorite anion in water.
Based on an oxidized irreversible ring-opening process of the spirolactam of rhodamine 6G to turn on the fluorescence pathway, a highly sensitive, selective fluorescent and easy accessible chemosensor for ClO(-) has been reported. Upon reaction of the chemosensor with ClO(-) ions, a fluorescent enhancement factor over 60-fold is observed. The chemosensor shows a remarkably high selectivity to discriminate between ClO(-) and other ROS, such as H(2)O(2), TBHP etc., and a wide range of the environmentally and biologically relevant anions and metal ions. The oxidized irreversible ring-opening process of the chemosensor also triggers a visible colorimetric change from colorless to pink, leading to production of both "naked-eye" and fluorimetric detection of ClO(-) anion. The detection limit is estimated to be 2 × 10(-8) M based on a signal-to-noise ratio of 3:1 method. The chemosensor can be used within a pH span of 6-11.5. The chemosensor also shows excellent performance in natural water samples.