Effects of PUVA on the epidermal melanocyte population in psoriatic patients.
The effect of PUVA treatment on the epidermal melanocyte system was studied in 24 skin biopsies from four male psoriatic patients. The patients had received 40 mg 8-methoxypsoralen and a phototoxic dose of UVA (2-12 joule/cm2), twice a week. Punch biopsies were taken from unaffected and psoriatic skin in the gluteal region before, and after three and nine treatments. The epidermal melanocytes were counted in dopa incubated split-skin preparations and the mitotic index of the keratinocytes was monitored as a control of the PUVA effect. The epidermal melanocyte number was essentially normal in non-treated psoriatic patients. During the PUVA treatment the melanin production and the DOPA activity of the melanocytes increased markedly. However, there was no significant change in the number of DOPA active melanocytes, either in the unaffected or the psoriatic skin. Thus, PUVA treatment is not necessarily associated with an increase in the number of active epidermal melanocytes.


Global Distribution of mcr Gene Variants in 214K Metagenomic Samples.
Since the initial discovery of a mobilized colistin resistance gene (mcr-1), several other variants have been reported, some of which might have circulated a while beforehand. Publicly available metagenomic data provide an opportunity to reanalyze samples to understand the evolutionary history of recently discovered antimicrobial resistance genes (ARGs). Here, we present a large-scale metagenomic study of 442 Tbp of sequencing reads from 214,095 samples to describe the dissemination and emergence of nine mcr gene variants (mcr-1 to mcr-9). Our results show that the dissemination of each variant is not uniform. Instead, the source and location play a role in the spread. However, the genomic context and the genes themselves remain primarily unchanged. We report evidence of new subvariants occurring in specific environments, such as a highly prevalent and new variant of mcr-9. This work emphasizes the importance of sharing genomic data for the surveillance of ARGs in our understanding of antimicrobial resistance. IMPORTANCE The ever-growing collection of metagenomic samples available in public data repositories has the potential to reveal new details on the emergence and dissemination of mobilized colistin resistance genes. Our analysis of metagenomes deposited online in the last 10 years shows that the environmental distribution of mcr gene variants depends on sampling source and location, possibly leading to the emergence of new variants, although the contig on which the mcr genes were found remained consistent.


Measurement for improvement: a survey of current practice in Australian public hospitals.
To identify patient safety measurement tools in use in Australian public hospitals and to determine barriers to their use. Structured survey, conducted between 4 March and 19 May 2005, designed to identify tools, and to assess current use of, levels of satisfaction with, and barriers to use of tools for measuring the domains and subdomains of: organisational capacity to provide safe health care; patient safety incidents; and clinical performance. Hospital executives, managers and clinicians from a nationwide random sample of Australian public hospitals stratified by state and hospital peer grouping. Tools used by hospitals within the three domains and their subdomains; patient safety tools and processes identified by individuals at these hospitals; satisfaction with the tools; and barriers to their use. Eighty-two of 167 invited hospitals (49%) responded. The survey ascertained a comprehensive list of patient safety measurement tools that are in current use for measuring all patient safety domains. Overall, there was a focus on use of processes rather than quantitative measurement tools. Approximately half the 182 individual respondents from participating hospitals reported satisfaction with existing tools. The main reported barriers were lack of integrated supportive systems, resource constraints and inadequate access to robust measurement tools validated in the Australian context. Measurement of organisational capacity was reported by 50 (61%), of patient safety incidents by 81 (99%) and of clinical performance by 81 (99%). Australian public hospitals are measuring the safety of their health care, with some variation in measurement of patient safety domains and their subdomains. Improved access to robust tools may support future standardisation of measurement for improvement.


[Circulatory insufficiency in the light of neuroendocrine and metabolic disorders].
Certain metabolic disorders characterizing disturbances both in neuroendocrine control and in metabolic processes at the cell and tissue levels were revealed in 472 patients with rheumatic heart disease, atherosclerotic cardiosclerosis, and cor pulmonale. The disturbance in the adrenal function was of a dissociated character, manifested by increase in sympathoadrenal and decrease in glucocorticoid activity. The indices of pentosophosphate cycle and erythrocyte and blood serum enzymes studied testify to deep changes in the state of the erythron, marked both by breaks and by adaptation to hypoxia caused by circulatory insufficiency.


The wear and tear of teeth.
A review is presented of the mechanical damage suffered by tooth crowns. This has been the subject of much recent research, resulting in a need to revise some of the thinking about the mechanisms involved. Damage is classified here by scale into macro-, meso- and microfracture. The focus is on the outer enamel coat because this is the contact tissue and where most fractures start. Enamel properties appear to be tailored to maximize hardness, but also to prevent fracture. The latter is achieved by the deployment of developmental flaws called enamel tufts. Macrofractures usually appear to initiate as extensions of tufts on the undersurface of the enamel adjacent to the enamel-dentine junction and extend from there into the enamel. Cracks that pass from the tooth surface tend to be deflected by an enamel region of high toughness; if they find the surface again, a chip (mesofracture) is produced. The real protection of the enamel-dentine junction here is the layer of decussating inner enamel. Finally, a novel analysis of mechanical wear (microfracture) suggests that the local toughness of the enamel is very important to its ability to resist tissue loss. Enamel and dentine have contrasting behaviours. Seen on a large scale, dentine is isotropic (behaving similarly in all directions) while enamel is anisotropic, but vice versa on a very small scale. These patterns have implications for anyone studying the fracture behaviour of teeth.


Successful treatment of paradoxical cerebral herniation by lumbar epidural blood patch placement: technical case report.
Death resulting from paradoxical cerebral herniation after the removal of cerebrospinal fluid from the lumbar cistern in a patient with a large craniectomy defect has recently been described. We report a case of successful treatment of this process by placement of a lumbar epidural blood patch. A 19-year-old man underwent a large craniectomy after a motorcycle-related trauma. He subsequently developed a progressive, large subgaleal fluid collection with very mild ventriculomegaly. A lumbar drain was placed, which resulted in paradoxical cerebral herniation. The patient was placed in the Trendelenberg position, and a lumbar epidural blood patch was placed. The next morning, there was complete resolution of the midline shift and restoration of visible basal cisterns. The patient has made an excellent recovery. We conclude that paradoxical cerebral herniation can be quickly reversed and successfully treated by placement of a lumbar epidural blood patch.


[Labeling cerebral activity with 3H-deoxyglucose after milacemide administration in the rat].
Milacemide (2-n-pentylaminoacetamide . HCl) is an anti-epileptic which improves the mood, vigilance and sociability of treated patients. By metabolic charting with radioactive deoxyglucose it is possible to estimate local consumption of glucose in the various regions of the brain in rats treated with milacemide in comparison with rats treated with a placebo. It would seem that milacemide exerts an appreciable activating effect principally on pathways with sensory functions. The activation of the metabolism of cerebral energy in these regions may explain the behavioural improvements observed in the rat and in the first clinical trials in man.


Overestimation and contraction biases of depth information stored in working memory depend on spatial configuration.
Depth perception is essential for effective interaction with the environment. Although the accuracy of depth perception has been studied extensively, it is unclear how accurate the depth information is stored in working memory. In this study, we investigated the accuracy and systematic biases of depth representation by a delayed estimation task. The memory array consisted of items presented at various stereoscopic depth positions, and the participants were instructed to estimate the depth position of one target item after a retention interval. We examined the effect of spatial configuration by comparing the memory performance in the whole-display condition where non-target memory items were present during retrieval with that in the single-display condition where non-target memory items were absent. In the single-display condition, we found an overestimation bias that the depth estimates were farther than the corresponding depth positions defined by disparity, and a contraction bias that the stored depth positions near the observer were overestimated and those far from the observer were underestimated. The magnitude of these biases increased with the number of to-be-stored items. However, in the whole-display condition, the overestimation bias was corrected and the contraction bias did not increase with the number of to-be-stored items. Our findings suggested that the number of to-be-stored items could affect the accuracy of depth working memory, and its effect depended crucially on whether the information of spatial configuration of memory display was available at the retrieval stage.


A new equation to predict peak VO2 in obese patients during cardiopulmonary exercise testing.
We aimed to develop an equation to predict peak VO2 in obese subjects undergoing CPET. In addition, we evaluated and compared three published equations. We randomized 346 obese subjects undergoing CPET into a group for developing the equation (n = 272) and a group for cross-validation (n = 74), compared through the Bland and Altman method. Height, sex and age were responsible for 85·5% of total variability of the peak VO2. Additional 1% and 0·7% of the variability were, respectively, explained by physical inactivity and diabetes. The equation devised was as follows: peakVO2mlmin-1=-677·8+(2135·9×heightm)+(706·8×sexmales=1;females=0)-(15·5×ageyears)-(161·1×physicalinactivityyes=1;no=0)-(176·3×diabetesyes=1;no=0). The mean difference between the estimated and measured peak VO2 was 7 ml min-1 , with a 23·9% bias. Published equations overestimated the peak VO2 by 35·3%, 49·1% and 46·2% bias. The equation developed in this study performed better in predicting peak VO2 in obese adults improving ramp protocol design and CRF evaluations in obese subjects.


Associations between gene expression profiles of invasive breast cancer and Breast Imaging Reporting and Data System MRI lexicon.
To evaluate whether the Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon could reflect the genomic information of breast cancers and to suggest intuitive imaging features as biomarkers. Matched breast MRI data from The Cancer Imaging Archive and gene expression profile from The Cancer Genome Atlas of 70 invasive breast cancers were analyzed. Magnetic resonance images were reviewed according to the BI-RADS MRI lexicon of mass morphology. The cancers were divided into 2 groups of gene clustering by gene set enrichment an alysis. Clinicopathologic and imaging characteristics were compared between the 2 groups. The luminal subtype was predominant in the group 1 gene set and the triple-negative subtype was predominant in the group 2 gene set (55 of 56, 98.2% vs. 9 of 14, 64.3%). Internal enhancement descriptors were different between the 2 groups; heterogeneity was most frequent in group 1 (27 of 56, 48.2%) and rim enhancement was dominant in group 2 (10 of 14, 71.4%). In group 1, the gene sets related to mammary gland development were overexpressed whereas the gene sets related to mitotic cell division were overexpressed in group 2. We identified intuitive imaging features of breast MRI associated with distinct gene expression profiles using the standard imaging variables of BI-RADS. The internal enhancement pattern on MRI might reflect specific gene expression profiles of breast cancers, which can be recognized by visual distinction.


Mucoid impaction: an unusual form of allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis.
We reported a child with cystic fibrosis (CF) who developed mucoid impaction related to allergic bronchopulmonary aspergillosis (ABPA). This is the first reported case of mucoid impaction related to ABPA in CF described to date in the literature. The case was successfully treated by corticosteroids and itraconazole therapy, but relapsed 6 months later. During exacerbation therapy, cataract formation complicated the corticosteroid treatment. We want to emphasize that 6-months therapy may be inadequate for the treatment of ABPA, and it is important to monitor for possible complications of corticosteroids therapy.


NUP62CL as an Immunological and Prognostic Biomarker of Oral Squamous Cell Carcinoma.
Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC. Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC. We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P<0.01), CD3+CD8+ T cells (P<0.01), CD56+ NK cells (P<0.05), CD68+CD86+ macrophages (P<0.01) and CD68+CD163+ macrophages (P<0.01), as well as the immune checkpoints, including PD-1 (P<0.001), PD-L1 (P<0.001), and CTLA-4 (P<0.001) protein expression. In conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients.


Potentially useful outcome measures for clinical research in pediatric neurosurgery.
The choice of outcome (or outcomes) and their measurement are critical for a sound clinical trial. Surgeons have traditionally measured simple outcomes such as death, duration of survival, or tumor recurrence but have recently developed more sophisticated measures of the effect of an intervention. Many outcome measures require a lengthy maturation process, which includes a determination of the instrument's validity, reliability, and sensitivity; thus, using established instruments rather than creating new ones is recommended. The authors illustrate several guidelines for the determination of appropriate outcome measures by using examples from their experience and describe several outcome measures that can be used in pediatric neurosurgery. These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).


Ectopic expression of von Hippel-Lindau tumor suppressor induces apoptosis in 786-O renal cell carcinoma cells and regresses tumor growth of 786-O cells in nude mouse.
The von Hippel-Lindau (VHL) is a known tumor suppressor that binds to alpha-subunits of hypoxia-inducible factors and induces ubiquitin-mediated degradation of the protein in an oxygen-dependent manner. VHL is also involved in the regulation of tumor angiogenesis, glycolysis, cell cycle regulation, and apoptosis. In the present study, we showed that ectopic expression of VHL induces apoptosis in renal cell carcinoma 786-O cells which contain only the mutant VHL, evidenced by TUNEL assay and DAPI staining. Furthermore, biochemical studies indicated that expression of VHL in 786-O cells results in both PARP and CPP32 cleavage, suggesting that VHL-induced apoptosis in 786-O cells is caspase dependent. Moreover, we also observed that apoptosis induced by ectopic VHL expression was associated with up-regulation of p27 as well as Bax, implicating the roles of these two proteins in VHL-induced apoptosis. The up-regulation of p27 and Bax by VHL was specific since we did not detect any changes in the level of other apoptotic factors including Fas and Bcl2 by the expression of VHL. We next examined the effect of VHL expression on the tumor growth of 786-O renal cell carcinoma cells in nude mouse. The results showed that injection of Ad.VHL adenovirus regresses the tumor growth of 786-O cells in nude mouse. The analysis by TUNEL assay as well as DAPI staining of 786-O tumors injected with Ad.VHL showed clear evidence of apoptosis. These results suggest that ectopic VHL expression induces apoptotic response in 786-O VHL mutant cells both in vitro and in vivo.


Presumed monozygotic twins develop following transfer of an in vitro-produced equine embryo.
An equine embryo produced by intracytoplasmic sperm injection (ICSI) was trans-cervically transferred to a recipient mare and pregnancy was confirmed via ultrasound examination on days 11, 12 and 15. On days 20 and 22, a single embryonic proper with a heartbeat was observed. On day 29, two embryos proper appeared during ultrasound examination, each possessing a heartbeat. Subsequent examinations on days 35 and 39 revealed continued viability and development of both embryos proper. On day 49, demise of both fetuses was present. Although no DNA analysis or post-partum examinations were performed, it is presumed that the fetuses were monozygotic twins based on membrane classification by ultrasound imaging as well as development occurring after the transfer of a single in vitro-produced embryo.


Chemical Analysis and Cytotoxic and Cytostatic Effects of Twelve Honey Samples Collected from Different Regions in Morocco and Palestine.
The aim of this in vitro study is to characterize the phenolic compounds of twelve honey samples collected from different locations in Palestine (H1-6) and Morocco (H7-12) and to evaluate their cytotoxic and cytostatic effects in cells from the human colorectal carcinoma cell line HCT-116 and breast cancer cell line MCF-7. Quantitative HPLC analysis revealed nine phenolic compounds in three Moroccan honey samples, namely, syringic acid, tannic acid, caffeic acid, ferulic acid, coumaric acid, gallic acid, rosmarinic acid, epicatechin, and pyrogallol. Syringic acid, abundant in numerous types of honey with strong antioxidant capacities, was present at values ranging between 0.10 mg/100 g and 1.24 mg/100 g of Daghmos (H11) and Kabbar (H10) samples, respectively. No significant reductions in cell viability were observed in both cell lines treated with the Palestinian samples as measured with MTT assay. Significant cytostatic effects were after treatment of HCT cells with Morar honey H1 with IC50 of 1789 μg/ml. Three Moroccan samples, H7 (Zaâtar), H9 (Bochnikha), and H10 (Kabbar), showed slight, but significant cytostatic effects in HCT cells. A strong correlation was observed between cytostatic activity of MCF cells and antioxidant content (phenols, flavonoids, and flavonol). Furthermore, a strong negative correlation was detected between the cytostatic activity in HCT cells and the contents of syringic acid (r= -0.756) and tannic acid (r= -0.610). These results indicate that the traditionally known anticancer effects of honey might be mediated in part through cytostatic effects.


Acute cholangitis induced by carbamazepine.
We report a case of a patient with fever and intrahepatic cholestasis induced by carbamazepine (CBZ). This adverse reaction has been described in only a single case. We observed complete resolution of the hepatic damage once the agent was discontinued. CBZ rechallenge was followed by recurrence of all symptoms and abnormalities. Hepatic function improved again when CBZ was discontinued.


Tandem cyclocondensation of 1,3-bis-sulfonylpropan-2-ones with arylaldehydes. One-pot synthesis of tris-sulfonyl 3-arylphenols.
One-pot tandem piperidinium acetate-mediated cyclocondensation of 1,3-bis-sulfonylpropan-2-ones with arylaldehydes generates tris-sulfonyl 3-arylphenols in moderate to good yields in refluxing toluene under easy-operational reaction conditions. A plausible mechanism is proposed and discussed. In the overall reaction process, water and sulfinic acid were generated as the byproducts. Various ammonium carboxylate-promoted conditions are investigated for one-pot [3 + 2 + 1]-benzannulation.


Comparative ultrastructural effects of aflatoxin B1 on mouse, rat, and human hepatocytes in primary culture.
Human, rat, and mouse hepatocytes in primary culture were treated with aflatoxin B1 (AFB1) and examined for ultrastructural alterations. As early as 1 h following in vitro exposure to AFB1, there were ultrastructural changes in the nuclei of rat and human hepatocytes. The most prominent change in the nuclei was a segregation of nucleolar components that resembled the segregation in liver cells of rats exposed to AFB1 in vivo. The nucleolar segregations were developed by incubating rat hepatocytes for 24 h in a medium containing as little as 0.01 micrograms of AFB1 per ml. The minimum concentration to induce the same change in human hepatocytes was 0.1 micrograms/ml. No distinct nucleolar alteration was observed in mouse hepatocytes incubated in a medium containing 10 micrograms of AFB1 per ml. Irregular nuclear chromatin condensation also developed in the cells exposed to a higher concentration of AFB1, whereas little damage was observed in mitochondria and lysosomes. The similarity in morphological changes between our in vitro model and in vivo models previously investigated indicates that the hepatocytes in primary culture maintain the biological properties necessary for carcinogen responses similar to liver cells in vivo. In addition, the morphological changes in cultured rat and mouse hepatocytes induced by AFB1 correlate with in vivo experiments insofar as mice are relatively resistant, whereas rats are sensitive to AFB1 carcinogenesis. Thus, cultured hepatocyte systems may be a valuable tool to study genetic damage which may lead to hepatocellular carcinomas in human and animal livers.


Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders.
Understanding the complexities of the human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations in replicating its intricacies, necessitating the development of in vitro models that can simulate its structure and function. Three-dimensional in vitro models, including organoids, cerebral organoids, bioprinted brain models, and functionalized brain organoids, offer promising platforms for studying human brain development, physiology, and disease. These models accurately replicate key aspects of human brain anatomy, gene expression, and cellular behavior, enabling drug discovery and toxicology studies while providing insights into human-specific phenomena not easily studied in animal models. The use of human-induced pluripotent stem cells has revolutionized the generation of 3D brain structures, with various techniques developed to generate specific brain regions. These advancements facilitate the study of brain structure development and function, overcoming previous limitations due to the scarcity of human brain samples. This technical review provides an overview of current 3D in vitro models of the human cortex, their development, characterization, and limitations, and explores the state of the art and future directions in the field, with a specific focus on their applications in studying neurodevelopmental and neurodegenerative disorders.


Etching-Free Ultrafast Fabrication of Self-Rolled Metallic Nanosheets with Controllable Twisting.
The rapid development of state-of-the-art nanotechnology is driven by the emerging novel nanofabrication methods, such as self-rolling of 2D materials or nanosheets. Nonetheless, the traditional chemical etching-based "roll-up" technologies suffer from a low fabrication efficiency and generally produce only scroll-like structures. In this work, we develop a versatile, ultrafast, and etching-free method to synthesize self-rolled metallic nanostructures through hydrogel surface buckling enabled exfoliation, which enables rapid exfoliation and self-rolling of metallic nanosheets at a rate about 1 to 2 orders of magnitude faster than other methods. Furthermore, we observe a scroll-helix-scroll transition through the twisting of the self-rolled nanosheets. Through extensive finite element simulations and experiments, we reveal the thermodynamics underpinning these configurational transitions.


Dengue Virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy.
Robust dengue virus (DENV) replication requires lipophagy, a selective autophagy that targets lipid droplets. The autophagic mobilization of lipids leads to increased β-oxidation in DENV-infected cells. The mechanism by which DENV induces lipophagy is unknown. Here, we show that infection with DENV activates the metabolic regulator 5' adenosine-monophosphate activated kinase (AMPK), and that the silencing or pharmacological inhibition of AMPK activity decreases DENV replication and the induction of lipophagy. The activity of the mechanistic target of rapamycin complex 1 (mTORC1) decreases in DENV-infected cells and is inversely correlated with lipophagy induction. Constitutive activation of mTORC1 by depletion of tuberous sclerosis complex 2 (TSC2) inhibits lipophagy induction in DENV-infected cells and decreases viral replication. While AMPK normally stimulates TSC2-dependent inactivation of mTORC1 signaling, mTORC1 inactivation is independent of AMPK activation during DENV infection. Thus, DENV stimulates and requires AMPK signaling as well as AMPK-independent suppression of mTORC1 activity for proviral lipophagy.IMPORTANCE Dengue virus alters host cell lipid metabolism to promote its infection. One mechanism for altered metabolism is the induction of a selective autophagy that targets lipid droplets, termed lipophagy. Lipophagy mobilizes lipid stores, resulting in enhanced β-oxidation and viral replication. We show here that DENV infection activates and requires the central metabolic regulator AMPK for its replication and the induction of lipophagy. This is required for the induction of lipophagy, but not basal autophagy, in DENV-infected cells.


[Molecular design of polymer-conjugated cytokines and its application for drug delivery systems].
In recent years, clinical application of recombinant cytokines has been expected as a novel drug for various diseases. However, cytokines have generally poor stability in vivo, so they required of very high doses to achieve sufficient clinical effect. In addition, because cytokines have pleiotropic functions, they would cause unfavourable side-effects. Therefore an drug delivery system (DDS) is necessary for clinical use, which stabilizes the cytokines and potentiates only the expected function from other unfavorable ones in vivo. Then we performed the chemical modification of cytokines with water-soluble polymers to overcome such problems as poor stability and pleiotropic activities. This approach includes some advantages that decrease renal excretion rate of proteins and prevent the degradation by proteases. This would result in prolonging the half-lives of bioactive proteins and potentiating their clinical effects. Interestingly, we found that the polymer-conjugated cytokines, that we named hybrid-cytokines, for instance, polyethylene glycol-modified interleukin-6 (PEG-IL-6), were able to increase selectively in their function of promoting platelet production, but not in other unfavourable functions. This effects were suggested for a result of the change in the systemic distribution pattern by pegylation of proteins. In this review, we proposed that the DDS using hybrid-cytokines would be able to increase the stability and regulate the spectrum of the functions of the cytokines by controlling the pharmacokinetics and pharmacodynamics in vivo. This will provide a fundamental information enabling us to design the hybrid-proteins applicable to therapeutic use.


Complete mitochondrial genome of the Tamiops swinhoei (Rodentia: Sciuridae).
The complete mitochondrial genome of Tamiops swinhoei has been determined in this study. It is 16,513 bp in size and consists of 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes and one non-coding region (D-loop). The overall base composition of the heavy strand of the T. swinhoei mitochondrial genome is A: 32.63%, T: 28.67%, C: 26.33% and G: 12.37%. The alignment of the Tamiops species control regions exhibited high genetic variability and rich A + T content (63.42%).


[The probability of obstructive sleep apnea disorders emergence by odds ratio of main risk factors].
The quality of sleep plays a serious role in the individual's daytime performace and state of health, there by it has a strong influence on the society. The present study measures the probability developing and severity of obstructive sleep apnea syndrome, - which belongs to group of disorders of the respiratory - through odds ratio of leading risk factors. 127 persons were examined in the test. The sleep structure test data were processed by polysomnographic screening device. The nutritional level of body in mass index (BMI), and the neck circumferences data were recorded in cm. On the basis of the examination the gender as a risk factor it can be said that the odds ratio for men compared to women, more than three times higher of emergence of disease. Men's chance of the emergence of serious disease is more than four times higher than women's chance. In the men's test group the most significant predictor of obstructive sleep apnea amongst the risk factors is the circumference according to odds ratio. In women's group the leader odds ratio is BMI. More than 50% of test goup don't report about daytime sleepiness, and this fact draws our attention to the role of risk factors' odds ratio in selection. Orv Hetil. 2017; 158(21): 823-828.


Compliance of Primary Care Providers With Gout Treatment Recommendations-Lessons to Learn: Results of a Nationwide Survey.
Objectives: Gout is generally managed in the primary health care sector. Compliance of primary care physicians with gout management recommendations has been shown to be insufficient in the past. The primary aims of this study were to assess primary care providers' knowledge regarding gout and to determine if their treatment decisions are influenced by recommendations. Facing considerable variations in postgraduate training options in Austria, we secondly looked for possible knowledge differences between urban and rural areas and eastern and western parts of Austria. Methods: We conducted a survey among 343 primary care physicians in Austria, using a questionnaire consisting of 10 questions on acute, intercritical and general gout management. Gout treatment recommendations served as the therapeutic gold standard. Results: Of the 343 physicians surveyed, 336 completed the questionnaire, leading to a very high return rate of 98%. 289 (86%) physicians were aware of the agreed-upon SUA target (<6 mg/dl). 323 (96.1%) reported change of therapy in case of missing this target. 112 (33.3%) physicians voted for long term ULT. No geographical differences in knowledge regarding gout or its management were revealed, except that colchicine was rated as being a safe medication significantly more often in rural areas (p = 0.035) and in western Austria (p = 0.014). Conclusion: As opposed to former studies, gout knowledge among primary care physicians has improved - however, treatment patterns are still not fully concordant with gout recommendations. Our findings may help to better tailor future postgraduate training to improve primary care physicians' education in gout.


Responsiveness to pamidronate treatment is not related to the genotype of type I collagen in patients with osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a heritable disorder characterized by increased bone fragility, low bone mass, dentinogenesis imperfecta, and blue sclerae. Most patients with OI have a mutation in either COL1A1 or COL1A2, which encode type I collagen. We screened these genes in Japanese patients with OI and compared their genotype and phenotype, focusing on the clinical response to treatment with pamidronate. Sequencing analysis of the genes in 19 families revealed 15 mutations, of which ten were missense mutations, thee were nonsense mutations, and two were frameshift mutations. Each of the 15 mutations was found in unrelated families, even though the patients were from a contiguous region surrounding our hospital. Substitutions of serine for glycine were the commonest mutation in both genes; notably, dentinogenesis imperfecta and fractures at birth were detected with higher frequencies in patients with this substitution when compared with other genotypes. The Z score of the bone mineral density of patients with this substitution was also lower than that of patients with other genotypes. Pamidronate treatment significantly increased the Z score in all patients, and increases in the Z score did not correlate with the OI types, causative genes, or genotype. In conclusion, the efficacy of pamidronate treatment does not seem to be related to the genotype of type I collagen in patients with OI.


Fabry-Perot Bragg grating nanoresonator with ultrahigh intrinsic Q based on low-loss silicon nitride.
Photonic integrated circuits based on ultralow loss silicon nitride waveguides have shown significant promise for realizing high-performance optical systems in a compact and scalable form factor. For the first time, we have developed a Fabry-Perot Bragg grating nanoresonator based on silicon nitride on silicon dioxide platform with an ultra-high intrinsic quality factor of 19.3 million. By combining the introduction of tapered grating between cavity and periodic Bragg grating, increasing the width of cavity to multi-mode region and optimized annealing strategy for Si3N4 film, the propagation loss is reduced to around 0.014 dB/cm. Fabry-Perot Bragg grating nanoresonator can be easily implemented in a simple straight waveguide occupying a minimal amount of space. Therefore, it is a key component to build a high performance photonic integrated circuit for many applications.


Training and mentorship as a tool for building African researchers' capacity in knowledge translation.
As one of the main knowledge producers, researchers can play an important role in contributing to efforts that bridge the gap between knowledge, policy and practice. However, for researchers to play this role, they need knowledge translation (KT) capacities that many typically lack. Furthermore, research has confirmed that little is known on KT training approaches for LMICs researchers and their effectiveness. This paper seeks to contribute to filling this knowledge gap on KT training approaches for LMIC researchers by assessing the effectiveness of a training and mentorship intervention to build African researchers' KT capacity. We conducted KT training and mentorship for 23 early and mid-career researchers from 20 universities in sub-Saharan Africa. This comprised a 5-day intense residential training workshop, followed by a 6-months mentorship. A pre- and post-training test was used to assess the immediate effect of the workshop. The intermediate effect of the training following a 6-month mentorship was assessed by the number of researchers who completed policy briefs during this period and those who participated in the webinar series conducted during this period. Overall, the aggregate average point change in the self-reported learning between the pre-training and the post-training survey was 1.9, which demonstrated the effectiveness of the training workshop. This was confirmed by a 33.7% increase in the aggregate average percentage of participants that responded correctly to questions assessing topics covered in the training between the pre-training and the post-training survey. During the mentorship period, 19 of the 23 researchers prepared and submitted complete drafts of their policy briefs within two months after the training. Fewer (4) researchers revised and submitted final policy briefs. More than half of the trained researchers participated in the webinars conducted in the first three months of the mentorship, whereas less than half of the researchers participated in the webinars conducted in the last three months. KT training and mentorship can be an effective intervention for addressing researchers' KT capacity gaps. For sustainability, KT training and mentorship need to be integrated in graduate training programmes in universities so that future LMIC researchers leave training institutions with the KT capacities they need for influencing policy and programme decisions and actions.


Effect of pancreatic glucagon and its 1-21 fragment on gastric emptying in man.
The effect of pancreatic glucagon (G) and its 1-21 fragment (G 1-21) on gastric emptying was studied in nine healthy volunteers. Gastric emptying of a 200-ml nutrient liquid meal was assessed during continuous infusion of physiologic saline, G, or G 1-21 in equimolar concentrations. The subjects were studied three times on separate days in randomized order. Gastric emptying was measured with a gamma camera technique. The emptying was diphasic in all studies, showing an initial plateau lasting 10-15 min followed by an exponential decline. During saline infusion the time necessary for 50% of the meal to leave the stomach was 32 +/- 4 min, compared with 30 +/- 4 min and 35 +/- 3 min during infusion of G and G 1-21, respectively. It is concluded that glucagon and its 1-21 fragment in physiologic concentrations do not seem to participate in the control of gastric emptying of a nutrient liquid meal.


Activity and stability of hammerhead ribozymes containing 2'-C-methyluridine: a new RNA mimic.
We propose 2'-C-methylnucleotides as a new class of 2'-modified RNA mimics. These analogues are expected to provide 2'-OH groups capable of reproducing the interactions observed in natural RNA and, due to the presence of the Me group, to possess increased stability towards nucleases. In this work, we investigate the catalytic activity and nuclease resistance of hammerhead ribozymes carrying 2'-C-methyluridines in positions 4 and 7 of the catalytic core. We describe the in vitro activity of these chimeric molecules and their stability in cell lysate, fetal calf serum, and cell culture medium. The data show that, when only position 4 is modified, activity decreases twofold; while, when both 4 and 7 positions are substituted, a sevenfold drop in activity is observed. Regarding biological stability, the main increase of the half-life time is observed when position 7 is modified. These results suggest that 2'-C-methylnucleotides may be useful in the design of chemically synthesized RNA mimics with biological activity.


[A Japanese pedigree with oculopharyngeal muscular dystrophy].
We investigated a Japanese pedigree with oculopharyngeal muscular dystrophy (OPMD) which included the probands of two sisters and a brother. Case 1 (Fig. 1): A woman born in 1940 at Fuji City, Shizuoka prefecture (Pacific coast side, which located about 80 miles west from Tokyo) was insidiously suffering from dysphagia and eye lid ptosis since her age of 40. She was admitted to Shizuoka Red Cross Hospital when 48 years old, because of difficulty of going upstairs. Neurological examination revealed severe eye lid ptosis without eye movement disorders, dysphagia, and moderate weakness on neck and proximal muscles of extremities without definite atrophy and fasciculation. In the laboratory data, serum creatine kinase level was slightly elevated to 215 U/l. Electromyographic findings showed myogenic pattern on the extremities but no evidence of the existence of myasthenia gravis and neurogenic involvement. Intranuclear tubular filaments were found in 3% of muscle fibers from her left biceps muscle. Case 2: The elder sister of the case 1 was suffering from eye lid ptosis without eye movement disorder and severe dysphagia since the age of 44. Case 3: The younger brother of the case 1 was suffering from dysphagia and proximal muscle weakness since the age of 40. We found eye lid ptosis, dysphagia and/or proximal muscle weakness in 24 cases (men: 12 cases, women: 12 cases) out of 50 examined members of this pedigree after their ages of 40 (Fig.3; family tree). It was concluded that this pedigree had cases of oculopharyngeal muscular dystrophy with autosomal dominant inheritance which was quite rare in Japanese.


A numerical study of the effect of axial acceleration on the responses of the cervical spine during low-speed rear-end impact.
A detailed, three-dimensional, head-neck (vertebral segments CO to C7) finite element model - developed and validated previously on the basis of the actual geometry of a cadaveric specimen - was used to evaluate the effect of cranial acceleration on the response of the cervical spine during low-speed, rear-end impact. Analyses were carried out to compare the predicted overall and segmental rotations, peak disc stresses, and capsular ligament strains of each motion segment during whiplash with or without cranial acceleration applied on the C7 inferior surface. The results show that, in the first 150 ms, the variation curves of predicted segmental rotational angles, disc stresses, and capsular strains for each motion segment overlapped well under the two conditions. However, after 150 ms, the capsular strains of C2 to C6 without cranial acceleration applied on C7 were all obviously lower than those with cranial acceleration applied, but the segmental rotational angles and disc stresses remain unaffected. It was implied that, although without cranial acceleration applied on C7, the relatively simple head-neck model could be used to reflect effectively the biomechanical response of the cervical spine during the initial stage (i.e. 150 ms) under low-speed, rear-end impact as well as the whole-human-body dummy model.


Staging and extended resection for pancreatic cancer.
Extended surgery is being widely performed to treat pancreatic cancer in Japan, but it has not been evaluated in the same way as in other countries. We, therefore, compared the Japanese Stage Classification (JPN-SC) with the Union Internationale Contre le Cancer Stage Classification (UICC-SC) in the surgical cases of pancreatic cancer treated in our department and then assessed the results of extended resection and associated problems. Problems existed in the resection rates and actuarial survival rates in stages II and III in the UICC-SC, and the JPN-SC was found to reflect more accurately the outcome. On the other hand, although improvements in curative resection and actuarial survival rate have been achieved as a result of extended resection in Japan, the outcome in JPN-SC surgical stage IVb and highly advanced cases in which these resections proved to be noncurative even though they were classified as surgical stage IVa was extremely poor. In the future, it will be necessary to decide on a single-stage classification that is accepted throughout the world and to conduct prospective studies matched to the degree of tumor progression.


Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model.
The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin's preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.


Identification of Leguminosae gums and evaluation of carob-guar mixtures by capillary zone electrophoresis of protein extracts.
A procedure for the extraction and capillary zone electrophoresis (CZE) separation of proteins from carob, guar and tara gums in a background electrolyte (BGE) of pH 9 containing 0.1% polyvinyl alcohol is described. The CZE protein profiles exhibit characteristic peaks for each one of the Leguminosae gums, which can be used to construct models capable of identifying samples of carob, guar and tara gums, and predicting the guar content in binary carob-guar mixtures of different geographical origin and harvested in different years. The classification and prediction models are constructed by using linear discriminant analysis (LDA) and multiple linear regression (MLR), respectively. An excellent resolution between the three categories is obtained with LDA, the model being capable of classifying samples with recognition and prediction capabilities of 100%. For MLR models constructed with carob-guar mixtures with and without a common history, the average of the calibration residuals are +/- 0.50 and +/- 0.90%, respectively (average values for the 2-20% guar range). For the later model, the detection limit was 3.2% guar (from the standard deviation of 18 mixtures with 2-4% guar, and for alpha = beta = 0.05).


A novel Mediterranean diet index from Lebanon: comparison with Europe.
To propose an index for assessing adherence to a Middle Eastern version of the Mediterranean diet as represented by the Traditional Lebanese Mediterranean diet (LMD), to evaluate the association between the LMD and selected European Mediterranean diets (EMD), and to examine socio-demographic and lifestyle correlates of adherence to Mediterranean diet (MD) among Lebanese adults. Using nationally representative dietary intake data of Lebanese adults, an index to measure Adherence to the LMD was derived. The choice of foods/food groups used for calculating the LMD score was based on results of previous factor analyses conducted on the same dataset. These foods/food groups included fruits, vegetables, legumes, olive oil, burghol, dairy products, starchy vegetables, dried fruits and eggs. Using Pearson's correlation and scores tertiles distributions agreement, the derived LMD index was compared to previously published EMD indexes from Greece, Spain, Italy, France and EPIC/Europe. Fruits, vegetables and olive oil were common denominators to most MD scores. Food groups, specific to the LMD, included burghol, dried fruits, and eggs. The LMD score significantly correlated with the EMD scores, while being closest to the Italian (r = 0.56) and farthest from the French (r = 0.21). Percent agreement between scores' tertile distributions and Kappa statistics confirmed these findings. Multivariate linear regressions showed that older age and higher educational levels were associated with increased adherence to all MDs studied. A novel LMD index was proposed to assess adherence to a Middle Eastern version of MD, complementing international efforts to characterize the MD and its association with disease risk.


[Excitotoxic effect of glutamate on the afferent neurons in guinea pigs].
To compare Glu-induced excitotoxic damage to the cochlear afferent neurons and changes of cochlear electrophysiology by directly injecting two different concentrations of glutamate into the inner ear of adult guinea pigs. Guinea pigs were injected high doses glutamate (Glu-H,20 mmol/L, 10 microl) and low doses of glutamate (Glu-L, 10 mmol/L, 10 microl) into the perilymph of scala tympani. The compound action potential (CAP) was recorded and pathologic changes were evaluated with light and transmission electronic microscope at various time points after the application of glutamate. Results The thresholds of the CAP of Glu-L group (10 mmoL/L, less than one day) and Glu-H group (20 mmol/ L) were significantly increased compared with those of the normal group (P <0.001). But the thresholds of CAP of glutamate application (10 mmol/L, more than one week) weren't significantly different from those of the normal group (P > 0.05). Some changes of the spiral ganglion cells of the cochlear axis were observed in the 2 drug groups by light microscope. There were some vacuoles in the cell body and condensation of nuclear chromatin, shallow cellar liquid. The ratios of pathological changes between the control group and Glu-H group of different concentrations were notably different (P < 0.05). The observation under transmission electronic microscope found disvolution or necrosis of afferent nerve endings, myelinated nerve fibers, and model spiral ganglion cells. The pathological changes of the Glu-H group were more serious than those of the Glu-L group (10 mmol/L). The pathological changes of the Glu-L group would recover in 4 weeks, but those of the drug group would gradually deteriorate and degeneration would become necrosis. The morphologic changes and functional losses of afferent neurons in guinea pigs were caused by glutamate in scala tympani. The low dose (10 mmol/L) had induced reversible damage to cochlear afferent neurons. The high dose (20 mmol/L) had triggered irreversible neurodegeneration.


[The results of the treatment of right ventricle myocardial infarction].
To present the results and experience in diagnosing and treating of patients with acute right ventricle infarction, during the period of hospitalization of one month, with adjuvant analyses of the obtained results in the period of fifteen years. Acute right ventricle infarction porved clinicaly, enzymologicaly, by ECG, echochardiographically or scintigraphically we treated with thrombolitic therapy within first six hours after admittion, with salvaged PTA in case of the cardiogenic shock or AV block II degrees-III degrees despite of thrommbolitic therapy, or with postponed PTA within first month of intrahospital treatment. In the period from 1990 to 2004, 3 225 patients of both sexes were treated for acute myocardial infarction at the different localization in patients' at the mean age of 53.7 +/- 5.8. One-hundred-thirty-nine (43.9%) patients were treated with thrombolitic therapy according to the speed up protocole. Heparin was administered to 160 (50.7%) patients with water load, and 17 (5.4%) patients had the primary percutaneous transluminal coronary angioplasty (PPTCA), so that the mechanical blood flow could be established, by the implantation of a stent when necessary. In 316 patients with right ventricle infarction, 58 (18.3%) had postponed and salvaged percutaneous transluminal coronary angioplasty (PTCA). Twenty-two (15.8%) patients had thrombolitic therapy, whereas 36 (22.5%) patients were treated with heparin. We had a successful balloon dilatation in 21 (36.2%), whereas 32 (55.2%) patients had 1-3 intracoronary stents inplanted, depending upon the necessity, and 5 (8.6%) patients from this group were sent to surgical intervention. In the group of 214 (67.7%) patients treated with heparin or thrombolitic therapy combined therapy, with PTCA, 12 (5.7%) patients died, whereas in the group of 124 (39.3%) patients treated only with heparin 26 (16.2%) patients died, statistically significant difference (p < 0.001, chi2 = 18.423). Was noticed n the group of 1 204 patients with inferoposterior infarction, 122 (10.1%) patients died. In the group of 316 patients with right ventricle infarction, 38 (12%) died. In the group of 888 control patients with inferoposterior infarction, but without right ventricle infarction, 84 (9.4%) patients died. In the group of 2 021 patients (62.2%) with anterior infarction, 248 (12.3%) died. CONCLUSION. The obtained results showed that the patients with right ventricle infarction, due to the great expansion of necrosis and the involvement of the inferoposterior wall of the left ventricle, as well as the ischemia of sinus and AV nodes, were the patients of a high risk. That was why it was essential to do urgent widening of the artery to reestablish blood flow either by using drugs or by means of mechanical methods.


When a wound is the harbinger of a serious underlying systemic illness.
A 55-year-old woman presented with progressive enlarging and painful non-healing ulcers on her bilateral lower extremities; biopsy was consistent with pyoderma gangrenosum. Workup for an underlying illness revealed a cavitary lung nodule and an ulcerating mass in the anal canal. Patient did not have any respiratory or gastrointestinal symptoms. Differential diagnosis included inflammatory bowel disease, rectal carcinoma or infection such as tuberculosis, fungal process. Histopathology did not reveal any malignancy, inflammatory bowel disease or infection. Serological studies were positive for perinuclear antineutrophil antibodies specific to proteinase-3 antigen, and the patient was ultimately diagnosed with granulomatosis with polyangiitis. Intravenous pulse dose steroids were initiated followed by monthly pulse cyclophosphamide for 6 months, resulting in rapid and significant improvement of the wounds.


Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with differences in magnitude between center and periphery.
The vertebrate retina develops from the center to the periphery. In amphibians and fish the retinal margin continues to proliferate throughout life, resulting in retinal expansion. This does not happen in mammals. However, some mammalian peripheral retinal pigment epithelial (RPE) cells continue to divide, perhaps as a vestige of this mechanism. The RPE cells are adjacent to the ciliary margin, a known stem cell source. Here we test the hypothesis that peripheral RPE is fundamentally different from central RPE by challenging different regions with microscopic laser burns and charting differential responses in terms of levels of proliferation and the regions over which this proliferation occurs. Microscopic RPE lesions were undertaken in rats at different eccentricities and the tissue stained for proliferative markers Ki67 and bromodeoxyuridine (BrdU) and the remodeling metalloproteinase marker 2 (MMP2). All lesions produced local RPE proliferation and tissue remodeling. Significantly more mitosis resulted from peripheral than central lesions. Unexpectedly, single lesions also resulted in RPE cells proliferating across the entire retina. Their number did not increase linearly with lesion number, indicating that they may be a specific population. All lesions repaired and formed apparently normal relations with the neural retina. Repaired RPE was albino. These results highlight regional RPE differences, revealing an enhanced peripheral repair capacity. Further, all lesions have a marked impact on both local and distant RPE cells, demonstrating a pan retinal signaling mechanism triggering proliferation across the tissue plane. The RPE cells may represent a distinct population as their number did not increase with multiple lesions. The fact that repairing cells were hypopigmented is of interest because reduced pigment is associated with enhanced proliferative capacities in the developing neural retina.


Impact of Four Rounds of Mass Drug Administration with Dihydroartemisinin-Piperaquine Implemented in Southern Province, Zambia.
Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.


Three-dimensional eye movement recordings during magnetic vestibular stimulation.
Human subjects placed in strong magnetic fields such as in an MRI scanner often feel dizzy or vertiginous. Recent studies in humans and animals have shown that these effects arise from stimulation of the labyrinth and are accompanied by nystagmus. Here, we measured the three-dimensional pattern of nystagmus using video eye tracking in five normal human subjects placed in a 7T MRI to infer which semicircular canals are activated by magnetic vestibular stimulation. We found that the nystagmus usually had a torsional as well as a horizontal component. Analysis of the relative velocities of the three eye movement components revealed that the lateral and anterior (superior) canals are the only canals activated, and by a similar amount.


Micromechanically-based formulation of the cooperative model for the yield behavior of starch-based nano-biocomposites.
The tensile yield stress of plasticized starch filled with montmorillonite has been studied as a function of the temperature and the strain rate and has been compared to the yield behavior of the original matrix. Aggregated/intercalated and exfoliated nano-biocomposites, obtained from different nanofillers, have been produced and tested under uniaxial tension (tensile test). To model the nanocomposite tensile yield stress behavior, a preexisting micro-mechanically based cooperative model, which describes properly the yield of semi-crystalline polymers has been modified. According to our development, the yield behavior of nano-biocomposites is strongly dependant on the clay concentration and exfoliation ratio. Based on the thermodynamics properties, an effective activation volume and effective activation energy are computed through the Takayanagi homogenization model. The predicted results for the yield stress at low strain rates and at different temperatures are in agreement with our experimental results.


Reduction in sarcoplasmic reticulum Ca2+-ATPase activity contributes to age-related changes in the calcium content and relaxation rate of rabbit aortic smooth muscle.
Elevated blood pressure is a common effect of aging that results from alterations in the calcium (Ca2+) homeostatic mechanisms in vascular smooth muscle cells. The sarcoplasmic reticulum is a primary subcellular organelle involved in Ca2+ homeostasis in vascular smooth muscle. This study was therefore undertaken to delineate possible age-associated changes that occur in the sarcoplasmic reticulum Ca2+ homeostatic mechanisms. Relaxation rates after phenylephrine-induced contractions in aortic smooth muscle from rabbits of increasing age were evaluated in the presence of thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor. In addition, electron probe X-ray microanalysis (EPMA) was used to analyze the total calcium content of the sarcoplasmic reticulum and cytosol in aortic smooth muscle from rabbits of various ages. The relaxation rate of rabbit aorta contracted with phenylephrine declined with age, the decline being progressively reduced when Ca2+ uptake by the sarcoplasmic reticulum was abolished by thapsigargin. EPMA measurements demonstrated an increased cytosolic calcium content and possibly reduced sarcoplasmic reticulum calcium content in arteries from older animals compared with arteries from juvenile animals. Reuptake of Ca2+ by the sarcoplasmic reticulum is necessary for optimal relaxation of rabbit aorta after a maximal, agonist-induced contraction. The present data suggest that impaired activity of the sarcoplasmic reticulum Ca2+ pump associated with aging may contribute to the increased cytosolic calcium content and elevated resting tone of aortic smooth muscle obtained from older rabbits.


Chinese hamster polyadenylated messenger ribonucleic acid: relationship to non-polyadenylated sequences and relative conservation during messenger ribonucleic acid processing.
We have further analyzed the metabolism of specific messenger ribonucleic acid (mRNA) sequences within the cytoplasmic and nuclear RNA of Chinese hamster ovary (CHO) cells by using a set of previously constructed complementary deoxyribonucleic acid (DNA) clones (Harpold et al., Cell 17:1025-1035, 1979) as specific molecular probes in a variety of RNA:DNA hybridization experiments. The majority of the labeled mRNA complementary to each of the nine clones was found in the polyribosomes, with some variation between individual sequences. The great majority of each specific mRNA labeled for 3 h or less was in the polyadenylated [poly(A)+] fraction. However, the amount of each sequence increased in the non-poly(A)+ [poly(A)-] fraction after very long label times, suggesting the derivation of the poly(A)- RNA from the poly(A)+ RNA. Eight of the nine mRNA's have cytoplasmic half-lives ranging from 8 to 14 h, whereas one of the mRNA's, the scarcest in the group, has a somewhat shorter half-life of approximately 3 h. The proportion of each of the specific long-lived mRNA's within the total labeled mRNA increased as a function of labeling time, indicating that a large fraction, probably greater than 50%, of the initially labeled poly(A)+ mRNA in CHO cells has a half-life of less than 3 h. A quantitative analysis of the kinetics of labeling of specific nuclear and cytoplasmic sequences indicated that a significant fraction of the mRNA sequences transcribed from genes containing these nine CHO sequences were successfully processed into mRNA. However, two of the CHO mRNA sequences were only partially conserved during nuclear processing to yield mRNA. These studies demonstrated that events at two post-transcriptional levels, differential nuclear processing efficiency of different primary transcripts and cytoplasmic stability of different mRNA's, can be involved in the determination of the cytoplasmic concentrations of different mRNA's.


Transposition of bacteriophage Mu in the Legionnaires disease bacterium.
Legionnaires disease is an acute respiratory disease that is often fatal for immunocompromised patients. The causative agent of this disease, Legionella pneumophila, is a Gram-negative bacterium that is present in a variety of aquatic environments. L. pneumophila is a facultative intracellular parasite; it grows within human phagocytic cells and eventually causes their destruction. In contrast to many other intracellular parasites, L. pneumophila is a Gram-negative bacterium that can be grown in standard microbiological culture medium. To determine the factors that enable this organism to enter, survive, and multiply within human mononuclear phagocytes, we chose bacteriophage Mu, a powerful genetic tool that transposes within the host cell genome, to generate insertion mutations and gene fusions in the Legionella genome. Certain derivatives of Mu are able to generate fusions between target genes and the lac operon from Escherichia coli. We have determined that although Mu is unable to attach to L. pneumophila or complete its life cycle within Legionella, it does transpose within the Legionella genome. Transposition was detected with a mini-Mu phage that carries the lac operon of E. coli.


Reactions of 1,3-Diphenyl Cyclopentadiene with α-Aryldiazo Ketones to Enable C-H Insertions versus [4 + 2]-Cycloadditions via Au Catalyst and P(C6F5)3 Additive, Respectively.
Two distinct reaction chemoselectivities were reported for the reactions of α-aryldiazo ketone with 1,3-diphenylcyclopentadiene using gold catalyst and phosphine additives, respectively. In the presence of gold catalyst, α-aryldiazo ketone forms gold carbenes initially that are trapped with this 1,3-disubstituted cyclopentadiene to afford C-H insertion products. In the presence of P(C6F5)3 additive, α-aryldiazo ketone forms diarylketenes initially at elevated temperature, which are further stabilized by P(C6F5)3 to secure their entity before proceeding to unprecedented [4C + 2C] cycloadditions.


Cell cycle regulation for meiosis in mammalian germ cells.
In mouse fetal gonads, germ cell development is accompanied by changes in cell cycle mode in response to external signals and intrinsic mechanisms of cells. During fetal development, male germ cells undergo G0/G1 arrest, while female germ cells exit the mitotic cell cycle and enter meiosis. In fetal testes, NANOS2 and CYP26B1 force germ cells to stay in G0/G1 arrest phase, preventing them from entering the meiotic cell cycle. In the fetal ovary, external signals, such as RA, BMP, and WNT, promote the competency of female germ cells to enter the meiotic cell cycle. MEIOSIN and STRA8 ensure the establishment of the meiotic cell cycle by activating meiotic genes, such that meiotic entry coincides with the S phase. This review discusses germ cell development from the viewpoint of cell cycle regulation and highlights the mechanism of the entry of germ cells into meiosis.


[The CEA test and other immunological tests as disease course controls in gastrointestinal adenocarcinoma].
161 patients with adenocarcinoma of the gastrointestinal tract were studied to determine the value of the CEA test and a battery of non-specific immunological tests during the course of the disease. The ability of these tests to detect a tumor recurrence in radically operated patients was evaluated. A false negative preoperative CEA value was found in 40% of the patients with gastric carcinoma and 32% with colorectal carcinoma. Patients with a negative preoperative CEA value, and those with only slightly elevated values, had a distinctly better prognosis regarding initial operability and tendency to postoperative recurrence than patients with primarily markedly elevated values. With few exceptions, the development of distant metastases was detected earlier and more easily with the CEA test than by the usual routine follow-up methods. However, in the event of isolated local recurrence the CEA test was positive in only 1 of 5 patients. This reflects the direct correlation between tumor size and CEA elevation. The CEA test is a valuable supplement in the follow-up of patients with gastrointestinal carcinoma.


Peroxisome biogenesis in the yeast Hansenula polymorpha is controlled by a complex set of interacting gene products.
We have studied the genetic interactions between mutant alleles in 12 genes, designated PER1-PER12, which are essential for peroxisome biogenesis in the yeast Hansenula polymorpha. Recessive mutations in any of these genes determined three different morphological phenotypes: (i) complete absence of peroxisomes (Per-); (ii) presence of small peroxisomes in conjunction with a major fraction of peroxisomal matrix proteins in the cytosol (Pim-); and (iii) presence of peroxisomes with aberrant crystalline matrix substructure (Pss-). Extensive complementation analysis showed many cases of noncomplementation--that is, diploids that contained both wild-type and mutant alleles of two different PER genes were unable to grow on methanol and showed peroxisomal defects. The observed cases of unlinked noncomplementation appeared to be gene and allele specific and were predominantly observed at lower temperatures (cold sensitive). The genetic results obtained were used to formulate a model of PER gene product interactions. In this model, five PER gene products are key or core components of the complex. Other PER gene products appear to play a more peripheral role.


Cisplatin in Liver Cancer Therapy.
Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used to treat advanced HCC. TACE and HAIC have long been the standard of care for patients with unresectable HCC but are limited to the treatment of intrahepatic lesions. Systemic chemotherapy with doxorubicin or chemohormonal therapy with tamoxifen have also been considered, but neither has demonstrated survival benefits. In the treatment of unresectable advanced HCC, cisplatin is administered transhepatic arterially for local treatment. Subsequently, for cisplatin-refractory cases due to drug resistance, a shift to systemic therapy with a different mechanism of action is expected to produce new antitumor effects. Cisplatin is also used for the treatment of liver tumors other than HCC. This review summarizes the action and resistance mechanism of cisplatin and describes the treatment of the major hepatobiliary cancers for which cisplatin is used as an anticancer agent, with a focus on HCC.


Glutathione levels and BAX activation during apoptosis due to oxidative stress in cells expressing wild-type and mutant cystic fibrosis transmembrane conductance regulator.
Cystic fibrosis is characterized by chronic inflammation and an imbalance in the concentrations of alveolar and lung oxidants and antioxidants, which result in cell damage. Modifications in lung glutathione concentrations are recognized as a salient feature of inflammatory lung diseases such as cystic fibrosis, and glutathione plays a major role in protection against oxidative stress and is important in modulation of apoptosis. The cystic fibrosis transmembrane conductance regulator (CFTR) is permeable to Cl(-), larger organic ions, and reduced and oxidized forms of glutathione, and the DeltaF508 CFTR mutation found in cystic fibrosis patients has been correlated with impaired glutathione transport in cystic fibrosis airway epithelia. Because intracellular glutathione protects against oxidative stress-induced apoptosis, we studied the susceptibility of epithelial cells (HeLa and IB3-1) expressing normal and mutant CFTR to apoptosis triggered by H(2)O(2). We find that cells with normal CFTR are more sensitive to oxidative stress-induced apoptosis than cells expressing defective CFTR. In addition, sensitivity to apoptosis could be correlated with glutathione levels, because depletion of intracellular glutathione results in higher levels of apoptosis, and glutathione levels decreased faster in cells expressing normal CFTR than in cells with defective CFTR during incubation with H(2)O(2). The pro-apoptotic BCL-2 family member, BAX, is also activated faster in cells expressing normal CFTR than in those with mutant CFTR under these conditions, and artificial glutathione depletion increases the extent of BAX activation. These results suggest that glutathione-dependent BAX activation in cells with normal CFTR represents an early step in oxidative stress-induced apoptosis of these cells.


Myelodysplastic syndrome following therapy for brain tumor--two case reports.
A 3-month-old boy and a 29-year-old woman presented with myelodysplastic syndrome (MDS) following therapy for primary malignant brain tumor. Both received intensive alkylating agent doses for induction and maintenance chemotherapy combined with craniospinal or cranial radiation for medulloblastoma and anaplastic astrocytoma, respectively. They developed refractory anemia and pancytopenia. Approximately 9 years after the completion of induction chemoradiotherapy, chromosomal analysis of bone marrow cells resulted in the diagnosis of MDS. The boy died of leukemic evolution 15 months later, the woman died of hematopoietic failure 3 months later. The most common symptom of MDS is refractory anemia, either alone or as part of bi- or pancytopenia. Clonal proliferation with chromosomal analysis of bone marrow cells establishes the diagnosis of MDS. Patients with malignant brain tumors are at risk of the development of MDS as a late complication of chemotherapy based on high cumulative doses of alkylating agents.


Long-term consequences of early sexual initiation on young adult health: A causal inference approach.
Although early sexual initiation has been linked to negative outcomes, it is unknown whether these effects are causal. In this study, we use propensity score methods to estimate the causal effect of early sexual initiation on young adult sexual risk behaviors and health outcomes using data from the National Longitudinal Study of Adolescent to Adult Health. We found that early sexual initiation predicted having 2 or more partners (for both males and females) and having a sexually transmitted infection in the past year (females only) but did not predict depressive symptoms in the past week (for either gender). These results underscore the importance of continued programmatic efforts to delay age of sexual initiation, particularly for females.


Genome-wide analysis of miRNA and mRNA transcriptomes during amelogenesis.
In the rodent incisor during amelogenesis, as ameloblast cells transition from secretory stage to maturation stage, their morphology and transcriptome profiles change dramatically. Prior whole genome transcriptome analysis has given a broad picture of the molecular activities dominating both stages of amelogenesis, but this type of analysis has not included miRNA transcript profiling. In this study, we set out to document which miRNAs and corresponding target genes change significantly as ameloblasts transition from secretory- to maturation-stage amelogenesis. Total RNA samples from both secretory- and maturation-stage rat enamel organs were subjected to genome-wide miRNA and mRNA transcript profiling. We identified 59 miRNAs that were differentially expressed at the maturation stage relative to the secretory stage of enamel development (False Discovery Rate (FDR)<0.05, fold change (FC)≥1.8). In parallel, transcriptome profiling experiments identified 1,729 mRNA transcripts that were differentially expressed in the maturation stage compared to the secretory stage (FDR<0.05, FC≥1.8). Based on bioinformatics analyses, 5.8% (629 total) of these differentially expressed genes (DEGS) were highlighted as being the potential targets of 59 miRNAs that were differentially expressed in the opposite direction, in the same tissue samples. Although the number of predicted target DEGs was not higher than baseline expectations generated by examination of stably expressed miRNAs, Gene Ontology (GO) analysis showed that these 629 DEGS were enriched for ion transport, pH regulation, calcium handling, endocytotic, and apoptotic activities. Seven differentially expressed miRNAs (miR-21, miR-31, miR-488, miR-153, miR-135b, miR-135a and miR298) in secretory- and/or maturation-stage enamel organs were confirmed by in situ hybridization. Further, we used luciferase reporter assays to provide evidence that two of these differentially expressed miRNAs, miR-153 and miR-31, are potential regulators for their predicated target mRNAs, Lamp1 (miR-153) and Tfrc (miR-31). In conclusion, these data indicate that miRNAs exhibit a dynamic expression pattern during the transition from secretory-stage to maturation-stage tooth enamel formation. Although they represent only one of numerous mechanisms influencing gene activities, miRNAs specific to the maturation stage could be involved in regulating several key processes of enamel maturation by influencing mRNA stability and translation.


Identification of a 5-Hydroxymethylation Signature in Circulating Cell-Free DNA for the Noninvasive Detection of Colorectal Cancer.
As a crucial epigenetic modification, DNA 5-hydroxymethylcytosine (5-hmC) plays a key role during colorectal cancer (CRC) carcinogenesis. Nevertheless, the levels of 5-hmC-related genes in the circulating DNA of CRC remain largely unknown. The GSE81314 dataset from the Gene Expression Omnibus (GEO), which was generated by chemical marking-based low-input shotgun sequencing to detect 5-hmC in circulating cell-free DNA (cfDNA) was used in the present study. The GSE81314 dataset includes data for 8 plasma samples from healthy individuals and 4 plasma samples from CRC patients. The difference in the 5-hmC levels in cfDNA between the CRC group and healthy individuals was analyzed by the differentially expressed genes (DEG) package. Weighted gene coexpression network analysis (WGCNA) was conducted to analyze gene coexpression modules associated with sample characteristics. DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes. WGCNA showed that the pink, purple, and brown modules, which contain 531 genes in total, were significantly correlated with CRC (0.66, 0.61, and -0.59, respectively). We used gene set enrichment analysis (GSEA) software to compare 5-hmC-related genes and pathways between CRC patients and healthy controls. We further performed a protein-protein interaction (PPI) analysis and identified 4 nodes (LCN2, LRG1, S100P, and TACSTD2) that played key roles in the network, and we analyzed the expression of these nodes S100P in the GEPIA database. Consistent with the 5-hmC levels in CRC patient plasma, our external validation results from the GEPIA and UALCAN databases showed that LCN2, LRG1, S100P, and TACSTD2 were highly expressed in CRC tissue compared with controls. The DNA promoter methylation levels of LCN2, LRG1, and S100P were lower in CRC tissue than in normal control tissue. The present findings suggest that abnormality in cell-free DNA hydroxylation in plasma may be associated with CRC. In addition, the 5-hmC levels of LCN2, LRG1, S100P, and TACSTD2 in circulating cfDNA may be used as potential noninvasive markers for CRC.


Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells.
The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8+ T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44hi CD24lo GD2+ phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8+ T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8+ T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses.


Infection with Blastocystis spp. and its association with enteric infections and environmental enteric dysfunction among slum-dwelling malnourished adults in Bangladesh.
Blastocystis spp. (Blastocystis) is a widely distributed gastrointestinal protist frequently reported in countries with tropical and sub-tropical climate. We sought to determine the factors associated with Blastocystis infection and investigate its role on biomarkers of intestinal health among slum-dwelling malnourished adults in Bangladesh. Total 524 malnourished adults with a body mass index ≤18.5 kg/m2 were included in this analysis. Presence of Blastocystis in feces was evaluated by TaqMan Array Card assays. Blastocystis was tested positive in 78.6% of the participants. Prevalence of infection with atypical strains of enteropathogenic Escherichia coli (aEPEC) (56% vs. 38%, p<0.001), and Trichuris trichiura (28% vs. 15%, p-value = 0.02) was significantly greater in adults with Blastocystis, while Giardia intestinalis was significantly lower (8% vs. 14%, p-value = 0.04) in Blastocystis positive adults. Malnourished adults who were living in households with high crowding index (aOR = 2.18; 95% CI = 1.11, 4.65; p-value = 0.03), and infected with aEPEC (aOR = 2.14; 95% CI = 1.35, 3.44; p-value = 0.001) and Trichuris trichiura (aOR = 1.97; 95% CI = 1.08, 3.77; p = 0.03) were more likely to be infected with Blastocystis. A significant negative relationship was observed between Blastocystis and fecal concentrations of alpha-1 antitrypsin (β = -0.1; 95% CI = -1.7, -0.1; p-value<0.001) and Reg1B (β = -3.6; 95% CI = -6.9, -3.0; p-value = 0.03). The study findings suggest that the presence of Blastocystis in human intestine influences gut health and may have potential pathogenic role in presence of other pathogens.


Quantifying Stochastic Processes in Shaping Dissolved Organic Matter Pool with High-Resolution Mass Spectrometry.
Natural dissolved organic matter (DOM) represents a ubiquitous molecular mixture, progressively characterized by spatiotemporal resolution. However, an inadequate comprehension of DOM molecular dynamics, especially the stochastic processes involved, hinders carbon cycling predictions. This study employs ecological principles to introduce a neutral theory to elucidate the fundamental processes involving molecular generation, degradation, and migration. A neutral model is thus formulated to assess the probability distribution of DOM molecules, whose frequencies and abundances follow a β-distribution relationship. The neutral model is subsequently validated with high-resolution mass spectrometry (HRMS) data from various waterbodies, including lakes, rivers, and seas. The model fitting highlights the prevalence of molecular neutral distribution and quantifies the stochasticity within DOM molecular dynamics. Furthermore, the model identifies deviations of HRMS observations from neutral expectations in photochemical and microbial experiments, revealing nonrandom molecular transformations. The ecological null model further validates the neutral modeling results, demonstrating that photodegradation reduces molecular stochastic dynamics at the surface of an acidic pit lake, while random distribution intensifies at the river surface compared with the porewater. Taken together, the DOM molecular neutral model emphasizes the significance of stochastic processes in shaping a natural DOM pool, offering a potential theoretical framework for DOM molecular dynamics in aquatic and other ecosystems.


Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.
Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-β1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-β1. Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.


A Pilot Study to Determine the Effect of an Educational DVD in Philippine Languages on Cancer Clinical Trial Participation among Filipinos in Hawai'i.
We conducted an experimental pilot study in an oncology clinic in Honolulu, Hawai'i to determine the effect of a culturally-tailored educational DVD on cancer clinical trial participation among Filipino cancer patients. Thirty-seven patients participated in the study, with 17 randomized into the control group (ie, usual education) and 20 into the intervention group (ie, usual education plus educational DVD). Participants completed pre- and post-educational questionnaires with items asking about understanding of several cancer topics, behavioral outcomes, and attitudes regarding several treatment and physician related topics. A Fisher's exact test was conducted to explore the association between enrollment into a clinical trial and group assignment. General linear models were created to determine significant differences between study groups in post-education response scores for each questionnaire item after controlling for age, gender, education, and pre-education response scores. Two participants from the control group and three participants from the intervention group enrolled into clinical trials. Results showed no significant association between clinical trial enrollment and study group assignment (P > .99). A significant difference was found between study groups on surety of joining the clinical trial suggested to them (P = .013). A multilingual educational DVD to supplement clinical trial education may positively influence Filipino cancer patients to move forward with the decision to join a cancer clinical trial. However, health literacy may serve as a major barrier to actual enrollment into the particular clinical trial available to a patient.


Optimizing Communication in Mechanically Ventilated Patients.
To describe the types of talking tracheostomy tubes available, present four case studies of critically ill patients who used a specialized tracheostomy tube to improve speech, discuss their advantages and disadvantages, propose patient selection criteria, and provide practical recommendations for medical care providers. Retrospective chart review of patients who underwent tracheostomy in 2010. Of the 220 patients who received a tracheostomy in 2010, 164 (74.55%) received a percutaneous tracheostomy and 56 (25.45%) received an open tracheostomy. Among the percutaneous tracheostomy patients, speech-language pathologists were consulted on 113 patients, 74 of whom were on a ventilator. Four of these 74 patients received a talking tracheostomy tube, and all four were able to speak successfully while on the mechanical ventilator even though they were unable to tolerate cuff deflation. Talking tracheostomy tubes allow patients who are unable to tolerate-cuff deflation to achieve phonation. Our experience with talking tracheostomy tubes suggests that clinicians should consider their use for patients who cannot tolerate cuff deflation.


Ultrasound-assisted and subcritical water extraction techniques for maximal recovery of phenolic compounds from raw ginger herbal dust toward in vitro biological activity investigation.
This study examined the impact of two green extraction techniques in order to maximize the usage and recovery of phenolic compounds from the by-product of the filter tea industry, the so-called ginger herbal dust. The main phenolic compounds extraction was performed by ultrasound-assisted extraction (UAE) with the sonication amplitude ranging from 20% to 100%, and the subcritical water extraction (SWE), with the temperature ranging from 120 °C to 220 °C. All obtained extracts were characterized in terms of extraction yield, total phenolic content (TPC), and 6-ginerol, 6-shogaol, and 8-ginerol contents using RP-HPLC-DAD. Based on the results, we selected the extract obtained from raw ginger herbal dust using a sonication amplitude of 100% for further biological investigation of the cytotoxic effect on short- and long-term cell viability on liver and pancreatic cancer cells. This extract contained high TPC concentration, and 6-gingerol (44.57 mg/gDE), 8-gingerol (8.62 mg/gDE), and 6-shogaol (6.92 mg/gDE).


The management of benign salivary disease: a case series.
There are many causes for benign salivary gland disease but the most common relate to inflammation and infection. This usually revolves around duct obstruction and a reduction in the normal salivary flow from the gland into the mouth. This leads to retention of saliva, proximal to the obstruction and ascending infection from the mouth, usually because of the decrease in salivary flow. The increase in tension behind the obstruction causes significant pain and swelling, along with the inevitable infection if the obstruction is not relieved. This paper discusses the various treatments available for benign salivary gland disease, the traditional methods of treatment through to the use of endoscopic techniques which are currently available, including a discussion about the use of sialoendoscopy.


SQUID-detected ultra-low field MRI.
MRI remains the premier method for non-invasive imaging of soft-tissue. Since the first demonstration of ULF MRI the trend has been towards ever higher magnetic fields. This is because the signal, and efficiency of Faraday detectors, increases with ever higher magnetic fields and corresponding Larmor frequencies. Nevertheless, there are many compelling reasons to continue to explore MRI at much weaker magnetic fields, the so-called ultra-low field or (ULF) regime. In the past decade many excellent proof-of-concept demonstrations of ULF MRI have been made. These include combined MRI and magnetoencephalography, imaging in the presence of metal, unique tissue contrast, and implementation in situations where a high magnetic field is simply impractical. These demonstrations have routinely used pulsed pre-polarization (at magnetic fields from ∼10 to 100mT) followed by read-out in a much weaker (1-100μT) magnetic fields using the ultra-sensitive Superconducting Quantum Interference Device (SQUID) sensor. Even with pre-polarization and SQUID detection, ULF MRI suffers from many challenges associated with lower magnetization (i.e. signal) and inherently long acquisition times compared to conventional >1T MRI. These are fundamental limitations imposed by the low measurement and gradient fields used. In this review article we discuss some of the techniques, potential applications, and inherent challenges of ULF MRI.


Pathogenicity evaluation of neuraminidase-negative H5 and H7 viruses in day-old chicks and adult chicken.
We evaluated the virulence of replication-competent NA-negative (no functional neuraminidase) avian influenza viruses in chicken of different ages. Interestingly, the virulence of a previously described NA-negative H5-virus (Kalthoff et al., J Virol 2013;87:13556) is very much age-dependent. Day-old-chicks succumb to a systemic infection, while chicken one week of age do not show any clinical signs at all. Therefore, the day-old-chick organism is most likely not able to restrict replication of the virus as older chicken do. In addition to virulence dependency on host age, the exchange of the H5 HA by an H7 HA for an H7NA-deleted HA reassortant remarkably led to a highly pathogenic phenotype even in adult chicken. This provides evidence, that the virulence of the H7-subtype is less dependent on the NA-protein than that of the H5-virus. These striking observations suggest that the HA/NA interplay might be governed by other mechanisms in HPAIV with the different serotypes H5 or H7.


Synthesis and characterization of a new layered fluoroaluminophosphate (C4H11NOH)3.5[Al4(PO4)5F] x 0.5H3O with extra-large 16-rings.
A new two-dimensional-layered fluoroaluminophosphate (C4H11NOH)3.5[Al4(PO4)5F] x 0.5H3O (denoted as AlPO-CJ20) with an Al/P ratio of 4:5 has been synthesized solvothermally by using 2-amino-2-methyl-1-propanol as the structure-directing agent. Its structure was determined by single-crystal X-ray diffraction analysis and further characterized by solid-state NMR techniques, including 27Al, 19F --> 27Al cross-polarization, and 31P magic angle spinning NMR. The alternation of Al-centered tetrahedra (AlO4 and AlO3F) and PO3(=O) tetrahedra gives rise to a new type of 4.6.16-net sheet. The inorganic sheets are stacked in an ABAB sequence along the [010] direction and further held together through strong H bonds between protonated template molecules and P=O groups in the inorganic layers. Except for Mu-4, AlPO-CJ20 is the second layered aluminophosphate with an Al/P ratio of 4:5, and it contains the largest pore opening of 16-rings in the known layered aluminophosphates. Furthermore, the coordination of Al and P of fluoroaluminophosphates is summarized. Crystal data: (C4H11NOH)3.5[Al4(PO4)5F] x 0.5H3O, monoclinic, C2/c (No. 15), a = 32.678(7) A, b = 12.956(3) A, c = 21.045(4) A, beta = 115.17(3) degrees, V = 8064(3) A3, Z = 8, R1 = 0.0837 [I > 2sigma(I)], and wR2 = 0.2428 (all data).