Immune response to pertussis vaccine in COPD patients.
Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4+ T cells (IFNγ, TNFα and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.


Bioequivalence studies for levothyroxine.
The Food and Drug Administration (FDA) Guidance for Bioavailability and Bioequivalence Studies for Levothyroxine has been challenged by companies that manufacture brand-name products. Their contention is that the current guidance does not adequately address the endogenous background levels of the drug, and that the ratios of the PK parameters, a basis for approval of equivalence, are not assessed correctly. In particular, they conclude that products that have a potency differing by 12.5% cannot be differentiated using the present guideline and criteria for acceptance of bioequivalence. They claim that such a difference can be a public health hazard because of the perception among practitioners that levothyroxine is a narrow therapeutic index drug. This article describes the procedure recommended in the current Guidance for Levothyroxine and demonstrates that the methods recommended are adequate and will accept products that are therapeutically equivalent. To date, no generic product accepted as equivalent using FDA Guidances has been shown to result in a safety and efficacy profile different from its brand counterpart.


Prevalence study of primary dystonia in Iceland.
In Iceland, the crude prevalence for all types of primary dystonia was 37.1/10(5) (confidence interval, 30.4-44.9). Focal dystonia had the highest prevalence (31.2/10(5)), followed by segmental (3.1/10(5)), multifocal (2.4/10(5)) and generalized dystonia (0.3/10(5)). Cervical dystonia was the most common focal dystonia (11.5/10(5)), followed by limb dystonia (8.0/10(5)), laryngeal dystonia (5.9/10(5)), blepharospasm (3.1/10(5)), and oromandibular dystonia (2.8/10(5)). The male:female ratio for all patients was 1:1.9 (P=0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3-82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar.


Knowledge and practices of generalist and specialist physicians regarding drug therapy for acute myocardial infarction.
The respective roles of generalist and specialist physicians in the care of patients is currently a matter of debate. Information is limited about the knowledge and practices of generalist and specialist physicians regarding conditions that both groups treat, such as myocardial infarction. We therefore surveyed 1211 cardiologists, internists, and family practitioners in the states of New York and Texas about four treatments demonstrated by randomized clinical trials to be associated with improved survival after myocardial infarction (thrombolytic therapy, immediate and long-term use of aspirin, and long-term use of beta-blockers) and two treatments for which such evidence is lacking (diltiazem for patients with pulmonary congestion and prophylactic lidocaine). We asked physicians about the effect of each treatment on survival and the likelihood that they would prescribe each class of drugs. For the four beneficial treatments, the cardiologists believed more strongly than the internists and family physicians that survival was improved by the treatment, and they were more likely to prescribe these drugs (P < 0.001). For example, 94.1 percent of cardiologists said they were very likely to prescribe thrombolytic agents to treat an acute myocardial infarction, as compared with 82.0 percent of internists and 77.3 percent of family practitioners. Conversely, for the two treatments for which trials showed no evidence of a survival benefit, cardiologists were less likely than internists and family practitioners to think there was such a benefit and less likely to prescribe the drugs (P < 0.001). For example, 4.7 percent of cardiologists reported that they were very likely to use prophylactic lidocaine, as compared with 13.1 percent of internists, and 16.5 percent of family practitioners. When we used logistic regression to adjust for potential confounders, all the differences between the cardiologists and the internists and family practitioners remained significant (P < 0.02). Internists and family practitioners are less aware of or less certain about key advances in the treatment of myocardial infarction than are cardiologists. This finding underscores the need to improve the dissemination of information from clinical trials to generalist physicians, particularly if they are to have an enlarged role in the evolving health care system.


Lower expression levels of the transforming growth factor beta receptor type II protein are associated with a less aggressive tumor phenotype and improved survival among patients with clear cell renal cell carcinoma.
Loss of expression of the transforming growth factor beta type II receptor (TbetaRII) has been implicated as an important event in renal carcinogenesis; however, its role as a potential prognostic factor remains poorly understood. Using archived tumor samples and long-term follow-up on a cohort of 280 clear cell renal cell carcinoma (ccRCC) patients treated with surgery from 1980 to 1998, we evaluated the association of TbetaRII expression and cancer-specific survival in both a univariate and multivariate setting. Low tumor expression of TbetaRII is associated with a less aggressive tumor phenotype at time of surgery. Moreover, those patients with lower levels of TbetaRII expression experience better cancer-specific survival than patients with higher levels of TbetaRII expression (log rank P = .034). Based on a Cox proportional hazard model adjusting for age, patients with tumors showing low (hazard ratio, 0.49; 95% confidence interval, 0.27-0.88) and moderate (hazard ratio, 0.7; 95% confidence interval, 0.40-1.23) TbetaRII expression are at decreased risk of RCC death compared with patients with tumors having high levels of TbetaRII expression. Adjustment for well-known pathologic predictors of RCC outcome attenuates the association of TbetaRII expression and ccRCC survival. Of interest, the association with TbetaRII expression appears more pronounced among those patients with tumors showing less aggressive phenotypes. Data from this investigation are the first to suggest that loss of TbetaRII expression is associated with improved ccRCC patient survival, especially among those patients with less aggressive disease profiles at time of surgery.


Induction of apoptosis by yomogin in human promyelocytic leukemic HL-60 cells.
Yomogin is an active compound isolated from Artemisia princep, a traditional Oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of yomogin on the cytotoxicity, induction of apoptosis, and putative pathways of its actions in human promyelocytic leukemia cells. Yomogin-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, formation of DNA ladders in agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine residues. We observed that yomogin caused activation of caspase-8, caspase-9, and caspase-3. A general caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk), almost completely suppressed the yomogin-induced DNA fragmentation. We further demonstrated that yomogin induced Bid cleavage, mitochondrial translocation of Bax from the cytosol, and cytochrome c release from mitochondria in a caspase-8-dependent manner. Taken together, our data indicate that yomogin is a potent inducer of apoptosis and facilitates its activity via caspase-8 activation, Bid cleavage, Bax translocation to mitochondria, and subsequent release of cytochrome c into the cytoplasm, providing a potential mechanism for the anticancer activity of yomogin.


Cation-Anion-CO2 Interactions in Imidazolium-Based Ionic Liquid Sorbents.
A series of functionalized N-alkylimidazolium based ionic liquids (ImILs) were designed, through anion (carboxylates and halogenated) and cation (N-alkyl side chains) structural modifications, and studied as potential sorbents for CO2 . The sorption capacities of as prepared bare ImILs could be enhanced from 0.20 to 0.60 molar fraction by variation of cation-anion-CO2 and IL-CO2 -water interaction. By combining NMR spectroscopy with molecular dynamics simulations, a good description of interactions between ImIL and CO2 can be obtained. Three types of CO2 sorption modes have been evidenced depending on the structure of the ImIL ion pair: Physisorption, formation of bicarbonate, and covalent interaction through the nucleophilic addition of CO2 to the cation or anion. The highest CO2 sorption capacity was observed with the ImIL containing the 1-n-butyl-3-methylimidazolium cation associated with the carboxylate anions (succinate and malonate). This study provides helpful clues for better understanding the structure-activity relationship of this class of materials and the ion pair influence on CO2 capture.


Tuberculosis vaccines and prevention of infection.
Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation.


[Chemical characteristics of the rhizosphere soil of water spinach cultivars differing in Cd accumulation].
A rhizobox experiment was conducted to investigate the chemical characteristics of the rhizosphere soils of two water spinach cultivars differing in Cd accumulation, QLQ (a low-Cd cultivar) and T308 (a high-Cd cultivar). The results showed that the diethylenetriamine pentacetate acid extractable Cd (DTPA-Cd) concentration in the rhizos-phere soil of QLQ was significantly higher than that of T308 (P < 0.05). pH and Eh in the rhizosphere soil of QLQ were significantly higher than those of T308 (P < 0.05), while EC was opposite. Contents of organic matter and dissolved organic matter (DOM) in the rhizosphere soil of QLQ were both higher than those of T308. In contaminated soil, the composition and concentration of low molecular weight organic acids in the rhizosphere between the two cultivars were both different. Acetic, propionic, citric and fumaric acids were detected in the rhizosphere soil of T308, and only citric and fumaric acids were detected in that of QLQ. The total concentration of low molecular weight organic acids in the rhizosphere soil of QLQ (1.93 nmol x g(-1) DM) was lower than that of T308 (15.11 nmol x g(-1) DM) (P < 0.01). Compared with the high-Cd cultivar (T308), the chemical characteristics of the rhizosphere soil of the low-Cd cultivar (QLQ) were obviously distinct, i. e., the relatively higher content of organic matter, the lower content of low molecular weight organic acids with a specific composition, less acidification of soil, and a lower ability in reduction, correspondingly lowering the mobility of Cd in soil and reducing Cd accumulation by plant.


[HPV and oropharyngeal squamous cell cancer in the 8th edition of the TNM classification].
The 8th edition of the TNM classification, available since January 1st, 2017, has changed the classification of variou s tumors. For head and neck squamous cell cancer (HNSCC) of the oropharynx (OPC) the new edition distinguishes between HPV-positive and HPV-negative disease to better reflect the prognostic implication of HPV associated disease. In many cases applying the new TNM-classification in HPV-positive OPC results in downstaging of formerly locally advanced disease, i. e. UICC III/ IV, into localized disease UICC stage I/II. However, the data suggesting a better prognosis for patients with HPV associated disease is based on retrospective analyses of studies not primarily designed to answer the question whether or not de-escalated treatment regimes will maintain this survival advantage. This article dedicated to continued medical education (CME) attempts to shed light on many clinical questions still remaining concerning pathology, tumor and life style factors affecting prognosis in this patient population. Only a good understanding of these questions will enable us to interpret data correctly and apply the best possible therapy to our patients according to their risk profile to ensure the best possible outcome.


Predictors of clinical pain intensity in patients with fibromyalgia syndrome.
Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up after-sensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.


Feline chronic gingivostomatitis is more prevalent in shared households and its risk correlates with the number of cohabiting cats.
The aim of this study was to determine whether feline chronic gingivostomatitis (FCGS) is more prevalent in shared vs single-cat households, whether the number of cohabiting cats or outdoor access represent risk factors for FCGS and whether the number of cohabiting cats is a useful prognostic indicator for standard surgical treatment. Cats diagnosed with FCGS (study group) in the past 5 years at a referral institution were identified. The number of cohabiting cats, outdoor access, number of other cohabiting cats diagnosed with FCGS, ⩾6 month surgical outcome, when applicable, and historical signs of upper respiratory disease among any of the cohabiting cats, as well as patient demographic information, were recorded. Data were collected from medical records and by means of a telephone interview with the owners. The same information was collected from a group of cats of similar demographic characteristics diagnosed with periodontal disease but free of FCGS (control group). Seventy-six cats were included, of which 36 (47%) had FCGS and 40 (53%) served as controls. Bivariate analysis showed that cats with FCGS were significantly more likely to come from shared households, and had significantly more total cats per household compared with controls. Multivariate analysis also showed that cats in shared households had a significantly increased odds of FCGS compared with those from single-cat households. Historical signs of upper respiratory disease and outdoor access among cats within the same household were not associated with FCGS. The number of cohabiting cats was not associated with surgical outcome. Cats with FCGS are more likely to live in shared households. The risk of FCGS correlates with the number of cohabiting cats. The epidemiological features of FCGS may support an infectious etiology. The number of cohabiting cats within a household is not a useful prognostic indicator for standard surgical treatment of FCGS.


[Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].
Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.


The management of DNA double-strand breaks in mitotic G2, and in mammalian meiosis viewed from a mitotic G2 perspective.
DNA double-strand breaks (DSBs) are extremely hazardous lesions for all DNA-bearing organisms and the mechanisms of DSB repair are highly conserved. In the eukaryotic mitotic cell cycle, DSBs are often present following DNA replication while, in meiosis, hundreds of DSBs are generated as a prelude to the reshuffling of the maternally and paternally derived genomes. In both cases, the DSBs are repaired by a process called homologous recombinational repair (HRR), which utilises an intact DNA molecule as the repair template. Mitotic and meiotic HRR are managed by 'checkpoints' that inhibit cell division until DSB repair is complete. Here we attempt to summarise the substantial recent progress in understanding the checkpoint management of HRR in mitosis (focussing mainly on mammals) and then go on to use this information as a framework for understanding the presumed checkpoint management of HRR in mammalian meiosis.


Research on the Visualization of Railway Signal Operation and Maintenance Based on BIM + GIS.
To adapt to the "fine" and "extensive" management characteristics of railway signal equipment operation and maintenance, achieving real-time and interactive monitoring of signal equipment operation status, and developing an integrated approach to equipment operation and maintenance, this paper takes a comprehensive management perspective. To create a lightweight BIM model, the Garland folding algorithm is utilized to simplify the IFC file format. Building on this approach, the data are divided based on building component division standards to obtain separate files containing geometric information and semantic attributes. The geometric information files are converted to a 3D Tiles format, combining BIM semantic attributes with semantic attribute files through an intermediate format. Dynamic data management is achieved by setting the octree space index structure in combination with a view-frustum culling algorithm. Then, the 3D Tiles target file is imported into the Cesium platform, and Node.js is used to achieve three-dimensional visualization of railway signal operation and maintenance. The proposed method is verified using an inbound signal as an example to assess its feasibility. The results demonstrate the potential of the proposed method to achieve stable integration between BIM equipment full lifecycle maintenance and GIS geographical space display. Railway signal equipment is endowed with comprehensive one-click information query functions for equipment positioning and spatial analysis, improving the efficiency and scientific decision-making level of equipment operation and maintenance.


Cyclic AMP and calcium in the transduction of hypothalamic neurohormone action in human pituitary tumors.
Although hypothalamic neurohormones were originally identified on the basis of their ability to influence hormone release from the target cells, it is at present clear that these agents are involved in the control of several biological processes that include cell proliferation and differentiation as well as hyperplasia and neoplastic transformation. Hypothalamic neurohormones bind specific receptors belonging to the G-protein-coupled receptor superfamily to generate intracellular effectors, in particular cAMP and calcium. Several in vivo and in vitro studies suggest the presence of functional and/or structural alterations in the receptor/effector molecules involved in the transduction of hypothalamic neurohormone action in the pituitary. The present study reports the frequent presence in pituitary tumors of cellular alterations that result in amplification of stimulatory signals, particularly activation of the cAMP-dependent pathway, and reduction of inhibitory inputs, both events having possible implications in tumor formation and/or progression.


Development and utilization of novel intron length polymorphic markers in foxtail millet (Setaria italica (L.) P. Beauv.).
Introns are noncoding sequences in a gene that are transcribed to precursor mRNA but spliced out during mRNA maturation and are abundant in eukaryotic genomes. The availability of codominant molecular markers and saturated genetic linkage maps have been limited in foxtail millet (Setaria italica (L.) P. Beauv.). Here, we describe the development of 98 novel intron length polymorphic (ILP) markers in foxtail millet using sequence information of the model plant rice. A total of 575 nonredundant expressed sequence tag (EST) sequences were obtained, of which 327 and 248 unique sequences were from dehydration- and salinity-stressed suppression subtractive hybridization libraries, respectively. The BLAST analysis of 98 EST sequences suggests a nearly defined function for about 64% of them, and they were grouped into 11 different functional categories. All 98 ILP primer pairs showed a high level of cross-species amplification in two millets and two nonmillets species ranging from 90% to 100%, with a mean of ∼97%. The mean observed heterozygosity and Nei's average gene diversity 0.016 and 0.171, respectively, established the efficiency of the ILP markers for distinguishing the foxtail millet accessions. Based on 26 ILP markers, a reasonable dendrogram of 45 foxtail millet accessions was constructed, demonstrating the utility of ILP markers in germplasm characterizations and genomic relationships in millets and nonmillets species.


The influence of physique on dose conversion coefficients for idealised external photon exposures: a comparison of doses for Chinese male phantoms with 10th, 50th and 90th percentile anthropometric parameters.
For evaluating radiation risk, the construction of anthropomorphic computational phantoms with a variety of physiques can help reduce the uncertainty that is due to anatomical variation. In our previous work, three deformable Chinese reference male phantoms with 10th, 50th and 90th percentile body mass indexes and body circumference physiques (DCRM-10, DCRM-50 and DCRM-90) were constructed to represent underweight, normal weight and overweight Chinese adult males, respectively. In the present study, the phantoms were updated by correcting the fat percentage to improve the precision of radiological dosimetry evaluations. The organ dose conversion coefficients for each phantom were calculated and compared for four idealized external photon exposures from 15 keV to 10 MeV, using the Monte Carlo method. The dosimetric results for the three deformable Chinese reference male phantom (DCRM) phantoms indicated that variations in physique can cause as much as a 20% difference in the organ dose conversion coefficients. When the photon energy was <50 keV, the discrepancy was greater. The irradiation geometry and organ position can also affect the difference in radiological dosimetry between individuals with different physiques. Hence, it is difficult to predict the conversion coefficients of the phantoms from the anthropometric parameters alone. Nevertheless, the complex organ conversion coefficients presented in this report will be helpful for evaluating the radiation risk for large groups of people with various physiques.


Non-response to questions about suicide ideation and attempts among veterans: Results from the National Health and Resilience in Veterans Study.
Veterans who decline to provide information on their history of self-injurious thoughts and behaviors (SITBs) may be at elevated suicide risk. We examined associations between non-response to a question assessing lifetime SITBs and proxy variables of suicide risk. In this population-based cross-sectional study of 4069 US veterans, responses to the Suicidal Behaviors Questionnaire-Revised were examined to group veterans into one of three categories: (1) denied lifetime SITBs, (2) reported lifetime SITBs, or (3) declined to respond. Overall, 69.5% of veterans denied a SITB history, 29.5% reported a SITB history, and 1.0% declined to provide information regarding SITBs. In adjusted analyses, veterans who declined to provide information on SITBs were significantly more likely than veterans who explicitly denied lifetime SITBs to screen positive for posttraumatic stress disorder; report lifetime non-suicidal self-injury; and report elevated levels of total trauma burden, externalizing behaviors, loneliness, received social support, and provided social support. Across these constructs, veterans who declined to provide SITB information were statistically indistinguishable from veterans who explicitly reported lifetime SITBs. Veterans who decline to provide information about suicidal thoughts and behaviors may represent a covert group at elevated risk for suicide.


Adults with autism spectrum conditions experience increased levels of anomalous perception.
Autism spectrum condition (ASC) is characterised by differences in social interaction and behavioural inflexibility. In addition to these core symptoms, atypical sensory responses are prevalent in the ASC phenotype. Here we investigated anomalous perception, i.e. hallucinatory and/or out of body experiences in adults with ASC. Thirty participants with an ASC diagnosis and thirty neurotypical controls completed the Cardiff Anomalous Perception Scale (CAPS) and the Social Responsiveness Scale (SRS-2). The CAPS is a 32-item questionnaire that asks participants to indicate whether or not they experience a range of anomalous and out of body experiences, and to rate how intrusive and distressing these experiences are. The SRS-2 asks participants to rate the extent to which they identify with a series of 65 statements that describe behaviours associated with the autism phenotype. We found that total CAPS score was significantly higher in the participants with ASC (mean = 14.8, S.D. = 7.9) than the participants without ASC (mean = 3.6, S.D. = 4.1). In addition, the frequency of anomalous perception, the level of distraction and the level of distress associated with the experience were significantly increased in participants with ASC. Importantly, both the frequency of anomalous perceptual experiences and the level of distress caused by anomalous perception in this sample of adults with ASC were very similar to that reported previously in a sample of non-autistic participants who were being treated in hospital for a current psychotic episode. These data indicate that anomalous perceptual experiences are common in adults with ASC and are associated with a high level of distress. The origins of anomalous perception in ASC and the implication of this phenomenon are considered.


Calcium salts deposition in rat connective tissue after the implantation of calcium hydroxide-containing sealers.
This study was conducted to observe the rat subcutaneous connective tissue reaction to implanted dentin tubes that were filled with mineral trioxide aggregate, Sealapex, Calciobiotic Root Canal Sealer (CRCS), Sealer 26, and the experimental material, Sealer Plus. The animals were sacrificed after 7 and 30 days, and the specimens were prepared for histological analysis after serial sections with a hard-tissue microtome. The undecalcified sections were examined with polarized light after staining according to the Von Kossa technique for calcium. At the tube openings, there were Von Kossa-positive granules that were birefringent to polarized light. Next to these granulations, there was irregular tissue, like a bridge, that was Von Kossa-positive. The dentin walls of the tubes exhibited a structure highly birefringent to polarized light, usually like a layer, in the tubules. These results were observed with all the studied materials, except the CRCS, which didn't exhibit any kind of mineralized structure. The results suggest that among the materials studied, the CRCS could have the least possibility of encouraging hard tissue deposition.


Aborted exenterative procedures in recurrent cervical cancer.
Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.


Shape and volume of lacunar infarcts: a 3D MRI study in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
The shape and exact size of lacunar infarcts have been investigated only postmortem. Recent imaging techniques based on triangulation and connectivity can now be used for 3D segmentation of cerebral lesions. The shape and size of lacunar infarcts was investigated using these techniques in 10 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients. We segmented 102 lacunar infarcts on T1-weighted images. The surface of the corresponding set of voxels was computed as a mesh of triangles. Thereafter, the shape of each lesion in 3D was visually analyzed by 2 investigators. The volume of lesions ranged from 10.5 to 1146 mm, with 93% of them having a volume <500 mm; 83% lacunar infarcts had a spheroid or ovoid shape, but 17% presented as sticks, slabs, or with a complex shape. Lesions with multiple components appeared larger than the others, and a tail extension was noticed in 13 of 102 lesions. These results suggest the following: (1) most lacunar infarcts in CADASIL have a volume far below one third of that of a sphere of 15 mm in diameter, the upper limit currently used for their identification on 2D imaging; (2) a significant proportion of lacunar infarcts have a shape distinct from the spheroid-ovoid morphology; and (3) lesions with a complex shape may result from the involvement of the largest small arteries, confluence of ischemic lesions, or secondary tissue degeneration. The segmentation of lacunar infarcts appears promising to better understand the pathophysiology of tissue lesions secondary to small vessel diseases.


Glucose-Derived Carbonaceous Nanospheres for Photoacoustic Imaging and Photothermal Therapy.
Carbon nanomaterials with small size and unique optical properties have attracted intensive interest for their promising biomedical applications. In this work, glucose-derived carbonaceous nanospheres (CNSs) with high photothermal conversion efficiency up to 35.1% are explored for the first time as a novel carbon-based theranostic agent. Different from most other carbon nanomaterials, the obtained CNSs are highly biocompatible and nontoxic because of their intrinsic hydrophilic property and the use of glucose as raw materials. Under near-infrared laser irradiation (808 nm, 6 W cm(-2)) for 10 min, less than 15% of PC-3M-IE8 cells exposed to CNSs aqueous dispersions (0.16 mg/mL) remained alive. After intravenous administration of CNSs aqueous dispersions into nude mice, the photoacoustic intensity of the tumor region is about 2.5 times higher than that of preinjection. These results indicate that CNSs are suitable for simultaneous photoacoustic imaging and photothermal ablation of cancer cells and can serve as promising biocompatible carbon-based agents for further clinical trials.


Left ventricular myxoma: echocardiographic diagnosis and review of the literature.
A 33 year old man with the findings of mild aortic stenosis had an echocardiographic diagnosis of left ventricular myxoma prolapsing through the aortic valve during each ventricular systole. The M-mode echocardiogram, B-scan ultrasonogram and angiograms of this patient are presented. The clinical characteristics in all the reported cases of left ventricular myxomas are reviewed.


Macroscopic dynamics of a trapped Bose-Einstein condensate in the presence of 1D and 2D optical lattices.
The hydrodynamic equations of superfluids for a weakly interacting Bose gas are generalized to include the effects of periodic optical potentials produced by stationary laser beams. The new equations are characterized by a renormalized interaction coupling constant and by an effective mass accounting for the inertia of the system along the laser direction. For large laser intensities the effective mass is directly related to the tunneling rate between two consecutive wells. The predictions for the frequencies of the collective modes of a condensate confined by a magnetic harmonic trap are discussed for both 1D and 2D optical lattices and compared with recent experimental data.


Rhodium bis(quinolinyl)benzene complexes for methane activation and functionalization.
A series of rhodium(III) bis(quinolinyl)benzene (bisq(x)) complexes was studied as candidates for the homogeneous partial oxidation of methane. Density functional theory (DFT) (M06 with Poisson continuum solvation) was used to investigate a variety of (bisq(x)) ligand candidates involving different functional groups to determine the impact on Rh(III)(bisq(x))-catalyzed methane functionalization. The free energy activation barriers for methane C-H activation and Rh-methyl functionalization at 298 K and 498 K were determined. DFT studies predict that the best candidate for catalytic methane functionalization is Rh(III) coordinated to unsubstituted bis(quinolinyl)benzene (bisq). Support is also found for the prediction that the η(2)-benzene coordination mode of (bisq(x)) ligands on Rh encourages methyl group functionalization by serving as an effective leaving group for SN2 and SR2 attack.


On-line solid-phase extraction and determination of paclitaxel in human plasma.
The application of coupled-column liquid chromatographic analysis to pharmacokinetic studies eliminates the need for sample clean-up from plasma. Considering lipophilic antineoplastic agents, we tested this approach to analyze paclitaxel under unfavourable circumstances (i.e., weekly low-dose regimen, plasma protein binding >90%, UV detection at 229 nm). The excellent quality control data (recovery: 95.6-100.7%, inter-assay relative standard deviation on 5 days: 1.3-3.2%, accuracy: 0.9-2.7%) and the detection limit of 19 nM indicates the usefulness of this method for the analysis of paclitaxel in plasma using on-line solid-phase extraction.


Transcriptome Analysis of Jojoba (Simmondsia chinensis) during Seed Development and Liquid Wax Ester Biosynthesis.
: Jojoba is one of the main two known plant source of natural liquid wax ester for use in various applications, including cosmetics, pharmaceuticals, and biofuel. Due to the lack of transcriptomic and genomic data on lipid biosynthesis and accumulation, molecular marker breeding has been used to improve jojoba oil production and quality. In the current study, the transcriptome of developing jojoba seeds was investigated using the Illunina NovaSeq 6000 system, 100 × 106 paired end reads, an average length of 100 bp, and a sequence depth of 12 Gb per sample. A total of 176,106 unigenes were detected with an average contig length of 201 bp. Gene Ontology (GO) showed that the detected unigenes were distributed in the three GO groups biological processes (BP, 5.53%), cellular component (CC, 6.06%), and molecular functions (MF, 5.88%) and distributed in 67 functional groups. The lipid biosynthesis pathway was established based on the expression of lipid biosynthesis genes, fatty acid (FA) biosynthesis, FA desaturation, FA elongation, fatty alcohol biosynthesis, triacylglycerol (TAG) biosynthesis, phospholipid metabolism, wax ester biosynthesis, and lipid transfer and storage genes. The detection of these categories of genes confirms the presence of an efficient lipid biosynthesis and accumulation system in developing jojoba seeds. The results of this study will significantly enhance the current understanding of wax ester biology in jojoba seeds and open new routes for the improvement of jojoba oil production and quality through biotechnology applications.


[Case of interstitial pneumonia induced by intravesical administration of Bacillus Calmette-Guerin].
An 81-year-old man with superficial bladder cancer, which was detected after he complained of hematuria and pain on urination, was treated 5 times with intravesical bacillus Calmette-Guerin (BCG) administration. Since he complained of a dry cough and dyspnea associated with severe hypoxemia, and had extensive bilateral pulmonary infiltrative shadows on his chest X-ray film, he was admitted to our hospital. He was treated with methylprednisolone under a diagnosis of interstitial pneumonia. Because BCG infection and/or bacterial pneumonia could not be denied, we administered antituberculosis agent and antibiotics. However, he died due to respiratory failure on 10th day after admission. Because a lymphocyte stimulation test for BCG was strongly positive, we established a diagnosis of interstitial pneumonia induced by intravesical administration of BCG. Because the mortality rate is high, the evaluation of interstitial pneumonia before administration of BCG is crucial.


Hospital Casemix Protocol - Medibank Private Perspective.
Hospital Casemix Protocol data provide a brief summary outlining morbidity data and costs associated with an episode of care. Federal government legislation requires that hospitals report this information to private health insurers who, in turn, merge these data with benefit outlays and report their findings to the Department of Health and Ageing (DoHA). This article gives a brief outline of the collection, cleansing and processing of these data and subsequent reporting to DoHA by Medibank Private, which accounts for approximately 30% of collected data.


Brain Network Constancy and Participant Recognition: an Integrated Approach to Big Data and Complex Network Analysis.
With the development of big data sharing and data standardization, electroencephalogram (EEG) data are increasingly used in the exploration of human cognitive behavior. Most of the existing studies focus on the changes of human brain network topology (the number of connections, degree distribution, clustering coefficient phantom) in various cognitive behaviors. However, there has been little exploration into the steady state of multi-cognitive behaviors and the recognition of multi-participant brain networks. To solve these two problems, we used EEG data of 99 healthy participants from the PhysioBank to study multi-cognitive behaviors. Specifically, we calculated the symbolic transfer entropy (STE) between 64 electrode sequences of EEG data and constructed the brain networks of various cognitive behaviors of each participant using the directed minimum spanning tree (DMST) algorithm. We then investigated the eigenvalue spectrum of the STE matrix of each individual's cognitive behavior. The results also showed that the spectrum distributions of different cognitive states of the same participant remained relatively stable, but those of the same cognitive state of different participants varied considerably, verifying the relative stability and uniqueness of the human brain network similar to a human's fingerprint. Based on these features, we used the spectral distribution set of 99 participants of various cognitive states as the original data set and developed a spectral distribution set scoring (SDSS) method to identify the brain network participants. It was found that most labels (69.35%) of the test participant with the highest score were identical to the labeled participant. This study provided further evidence for the existence of human brain fingerprints, and furnished a new approach for dynamic identification of brain fingerprints.


[Halle physicians in the pre- and early history of modern endocrinology].
Textbooks of endocrinology separate the modern development (since 1920) from a pre- and an early history of this discipline. Researching facts of the universities of Wittenberg and Halle appear in the lists of the two periods of inauguration. Pioneers as Ernst Joseph lesser, Ernst laqueur and Frigyes Verzár place the university of Halle in the range of early descriptions of endocrine data.


Epitope mapping of horseradish peroxidase with use of monoclonal antibodies.
Nine mouse monoclonal antibodies (MAbs) to horseradish peroxidase (HRP) were used to develop an epitope map of the enzyme. The results of a competitive binding assay indicated three distinct patterns of reactivity. Two groups of MAbs (I and III) recognized epitopes located in separate antigenic regions on the molecule; another (II) bound to sites that overlapped with epitopes in either region I or III. Further definition of these regions was obtained by analyzing the MAbs for their binding to isolated heme, other peroxidases and heme-containing proteins, and to denatured and apo-HRP. None of the group I MAbs bound heme, suggesting that this region was removed from the active site of the enzyme. All of the group II and III MAbs bound heme as well as the other peroxidases and heme-containing proteins, indicating that they recognized heme-associated epitopes at or near the active site. Only one MAb (2A2) in groups II and III bound to apo-HRP but not to denatured HRP; it was also the only MAb in the entire panel that inhibited the catalytic activity of HRP. This suggests that the epitope recognized by 2A2 involves both the heme moiety and a conformationally dependent protein determinant near the active site.


Detection of multidrug resistance associated P-170 glycoprotein in previously untreated non small cell lung cancer.
Samples of Non Small Cell Lung Cancer (NSCLC) and normal bronchial tissue obtained in patients submitted to radical surgery and without previous exposure to cytotoxic drugs were investigated for the expression of P-170 glycoprotein using C-219 monoclonal antibody and an immunohistochemistry technique. In normal bronchial tissue the immunostaining was confined to the lumenal surface of the epithelium. Fifteen out of 86 NSCLC had more than 1/4 of examined cells positive for P-170 glycoprotein, but the heterogeneity of the expression ranged from rare scattered cells to a positive pattern for nearly all cells considered, without any relationship with pathologic and clinical prognostic variables.


Robust consensus tracking control of multiple mechanical systems under fixed and switching interaction topologies.
Consensus tracking problems for multiple mechanical systems are considered in this paper, where information communications are limited between individuals and the desired trajectory is available to only a subset of the mechanical systems. A distributed tracking algorithm based on computed torque approach is proposed in the fixed interaction topology case, in which a robust feedback term is developed for each agent to estimate the external disturbances and the unknown agent dynamics. Then the result is extended to address the case under switching interaction topologies by using Lyapunov approaches and sufficient conditions are given. Two examples and numerical simulations are presented to validate the effectiveness of the proposed robust tracking method.


Charged lithium adsorption on pristine and defective silicene: a theoretical study.
We investigated by first principle calculations the adsorption of Liq(q= -1, 0 or +1) on a silicene single layer. Pristine and three different defective silicene configurations with and without Li doping were studied: single vacancy (SV), double vacancy (DV) and Stone-Wales (STW). Structural studies and the adsorption energies of various sites were obtained and compared in order to understand the stability of the Li on the surface. Moreover, electronic structure and charge density difference analysis were performed before and after adsorption at the most stables sites, which showed the presence of a magnetic moment in the undoped SV system, the displacement of the Fermi level produced by Li doping and a charge transfer from Li to the surface. Additionally, quantum capacity (QC) and charge density studies were performed on these systems. This analysis showed that the generation of defects and doping improves the QC of silicene in positive bias, because of the existence of 3p orbital in the zone of the defect. Consequently, the innovative calculations performed in this work of charged lithium doping on silicene can be used for future comparison with experimental studies of this Li-ion battery anode material candidate.


Stress-induced protein CSP 310: a third uncoupling system in plants.
Addition of the cold-stress-related protein CSP 310 to mitochondria isolated from winter wheat ( Triticum aestivum L. cv. Zalarinka), winter rye ( Secale cereale L. cv. Dymka), maize ( Zea mays L. cv. VIR 36) and pea ( Pisum sativum L. cv. Marat) caused an increase in non-phosphorylative respiration. This increase was inhibited by KCN, indicating that the protein is not a CN-resistant alternative oxidase. Unlike plant mitochondrial uncoupling proteins such as PUMP, the uncoupling action of CSP 310 did not depend on the presence of free fatty acids in the incubation medium. We propose that the mechanism of the uncoupling action of CSP 310 differs from that of other known plant uncoupling systems and that the CSP 310 uncoupling system is a third uncoupling system in cereals.


Human exposure to mercury and silver released from dental amalgam restorations.
In 35 healthy individuals, the number of amalgam surfaces was related to the emission rate of mercury into the oral cavity and to the excretion rate of mercury by urine. Oral emission ranged up to 125 micrograms Hg/24 h, and urinary excretions ranged from 0.4 to 19 micrograms Hg/24 h. In 10 cases, urinary and fecal excretions of mercury and silver were also measured. Fecal excretions ranged from 1 to 190 micrograms Hg/24 h and from 4 to 97 micrograms Ag/24 h. Except for urinary silver excretion, a high interplay between the variables was exhibited. The worst-case individual showed a fecal mercury excretion amounting to 100 times the mean intake of total Hg from a normal Swedish diet. With regard to a Swedish middle-age individual, the systemic uptake of mercury from amalgam was, on average, predicted to be 12 micrograms Hg/24 h.


A Case of Risperidone Induced Stuttering as a Paradox.
The main feature of stuttering is the disturbance in terms of both timing and fluency of speech inappropriate with the age. This disturbance is characterized with the repetition and prolongation of sounds and syllables. There are two types of stuttering as acquired and developmental. Acquired stuttering may begin suddenly at any age and may be seen rarely due to the adverse effects of drugs. Stuttering induced by antipsychotics may develop very rarely. Risperidone is a strong antagonist of dopamin 2 (D2) and serotonin 2A (5 HT2A) and shows a high affinity for α1 and α2 noradrenaline receptors. It's used in a wide spectrum including psychotic disorders, mood disorders, and behavioral disorders, even for the treatment of stuttering. Risperidone treats the symptoms of stuttering by the antagonism of D2 receptors with an increase in striatal metabolism. In literature, we haven't observed any other case reports except the two stuttering cases with psychotic disorders due to the short term and high-dose risperidone treatment. In our case, stuttering adverse effect of chronic low-dose risperidone treatment is remarkable that is discussed for the first time. As well as the use of risperidone for the treatment of stuttering, stuttering adverse effect seems to be interesting as a paradox.


Prevascular structures promote vascularization in engineered human adipose tissue constructs upon implantation.
Vascularization is still one of the most important limitations for the survival of engineered tissues after implantation. In this study, we aim to improve the in vivo vascularization of engineered adipose tissue by preforming vascular structures within in vitro-engineered adipose tissue constructs that can integrate with the host vascular system upon implantation. Different cell culture media were tested and different amounts of human adipose tissue-derived mesenchymal stromal cells (ASC) and human umbilical vein endothelial cells (HUVEC) were combined in spheroid cocultures to obtain optimal conditions for the generation of prevascularized adipose tissue constructs. Immunohistochemistry revealed that prevascular structures were formed in the constructs only when 20% ASC and 80% HUVEC were combined and cultured in a 1:1 mixture of endothelial cell medium and adipogenic medium. Moreover, the ASC in these constructs accumulated lipid and expressed the adipocyte-specific gene fatty acid binding protein-4. Implantation of prevascularized ASC/HUVEC constructs in nude mice resulted in a significantly higher amount of vessels (37 ± 17 vessels/mm(2)) within the constructs compared to non-prevascularized constructs composed only of ASC (3 ± 4 vessels/mm(2)). Moreover, a subset of the preformed human vascular structures (3.6 ± 4.2 structures/mm(2)) anastomosed with the mouse vasculature as indicated by the presence of intravascular red blood cells. Our results indicate that preformed vascular structures within in vitro-engineered adipose tissue constructs can integrate with the host vascular system and improve the vascularization upon implantation.


Ring finger protein 152 inhibits colorectal cancer cell growth and is a novel prognostic biomarker.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. RING finger-related E3 ubiquitin ligases play a role in tumorigenesis and can function either as oncogenes or tumor suppressors based on their target proteins. Here, we show that the expression of RNF152, a ring finger protein, in CRC tissues was significantly reduced compared with adjacent non-cancerous tissues. High expression levels of RNF152 correlated with better prognosis in patients with colorectal cancer. Low expression of RNF152 correlated with lymphatic metastasis. Overexpression of RNF152 inhibited CRC cell proliferation both in vitro and in vivo by inactivating the mechanistic target of rapamycin complex 1 (mTORC1) and inducing autophagy and apoptotic cell death. This strong inhibition was dependent on the E3 ligase activity of RNF152. Ectopic expression of the RNF152-CS-mutant, which lacks E3 ligase activity, significantly restored the proliferation ability of CRC cells. Our findings showed that RNF152 inhibits colorectal cancer growth and may be a novel prognostic biomarker for the treatment of CRC.


Anti-NMDA Receptor Encephalitis Presenting as an Acute Psychotic Episode in a Young Woman: An Underdiagnosed yet Treatable Disorder.
Anti-NMDA receptor (NMDAR) encephalitis is a recently identified autoimmune disorder with prominent psychiatric symptoms. Patients usually present with acute behavioral change, psychosis, catatonic symptoms, memory deficits, seizures, dyskinesias, and autonomic instability. In female patients an ovarian teratoma is often identified. We describe a 32-year-old woman who presented with acute psychosis. Shortly after admission, she developed generalized seizures and deteriorated into a catatonic state. Although ancillary tests including MRI, electroencephalogram, and cerebrospinal fluid (CSF) analysis were unremarkable, the presentation of acute psychosis in combination with recurrent seizures and a relentless course suggested autoimmune encephalitis. The patient underwent pelvic ultrasound which disclosed a dermoid cyst and which led to an urgent cystectomy. Plasmapheresis was then initiated, yielding partial response over the next two weeks. Following the detection of high titers of anti-NMDAR antibodies in the CSF, the patient ultimately received second line immunosuppressive treatment with rituximab. Over several months of cognitive rehabilitation a profound improvement was eventually noted, although minor anterograde memory deficits remained. In this report we call for attention to the inclusion of anti-NMDAR encephalitis in the differential diagnosis of acute psychosis. Prompt diagnosis is critical as early immunotherapy and tumor removal could dramatically affect outcomes.


[Rosenmüller valve during endoscopic dacryocystorhinostomy in treating refractory nasolacrimal duct obstruction].
The objective of this study was to assess the efficacy of exposing Rosenmüller valve during endonasal endoscopic dacryocystorhinostomy (EES-DCR) in treating refractory nasolacrimal duct obstruction. Thirty six patients (47 eyes) with refractory nasolacrimal duct obstruction were entered into this study, including 13 patients (15 eyes) underwent nasal lacrimal duct intubation before, 18 patients (26 eyes) with small lacrimal sac, 2 patients underwent DCR before, 1 patient with functional nasal lacrimal duct obstruction, 1 patient with lacrimal mucocele, 1 patient with nasal trauma. During the DCR, the bone window was enlarged as wide as possible and the valve of Rosenmüller was exposed. The intubation of the lacrimal apparatus was performed if the lacrimal sac was very small and the Rosenmüller valve was tight. Functional endoscopic sinus surgery and septoplasty were performed simultaneously if necessary. Postoperatively, each patient was assessed by the symptom and nasal endoscopy. The postoperative follow-up period ranged from 3 to 36 months. Thirty two patients(89.4%, 42/47 eyes) were cured, which presented as the disappearance of symptoms, the patency of the lacrimal ostium and the lacrimal duct irrigation was clear. One patient (2.1%, 1/47 eyes) was improved, which presented as the improvement of symptoms, a few hypertrophic scar around the lacrimal ostium and the lacrimal duct irrigation was clear. Four cases failed (8.5%, 4/47), which presented as symptomatic and obstruction of the lacrimal ostium. The total effective rate reached to 91.5%. No serious postoperative complications were found in all cases. To expose Rosenmüller valve during endoscopic DCR in treating patients with refractory nasolacrimal duct obstruction could obviously increase the operative success rate, fewer complications, with no facial surgical scar. It is an ideal way to treat the refractory nasolacrimal duct obstruction.


The Biomechanical Properties of Meshed versus Perforated Acellular Dermal Matrices (ADMs).
Acellular dermal matrices (ADMs) are used for soft tissue augmentation across surgical specialties. Since allograft incorporation depends on direct opposition between the ADM and a vascular bed, seroma formation can be detrimental to incorporation. Since most ADM products are available in many meshed and perforated forms, there is a lack of consistency between manufacture designs. We set out to determine the fluid egress properties and increase in surface area resulting from common cut patterns. Three ADM cut patterns were studied: 1 meshed and 2 perforated. We calculated the surface area of these modified ADM samples. Fluid was passed through each ADM, and time required for fluid passage was recorded. An ANOVA (P < 0.05) was used to determine if there was a significant difference in egress properties across the 3 patterns. Meshing in a 1:1 pattern resulted in a 97.50% increase in surface area compared with the uncut product. In comparison, only a 0.30% increase resulted from Perforation Pattern #1 and a 0.59% increase resulted from Perforation Pattern #2. There was a significant difference in egress properties across the three cut patterns (P = 0.000). The average egress time of Mesh Pattern #1 was 1.974 seconds. The average egress time of Perforation Pattern #2 was 6.504 seconds, and of Perforation Pattern #1 was 10.369 seconds. Quantitative comparison revealed that meshing ADM significantly improves fluid egress and increases the surface area. Therefore, the use of meshed ADM tissue could improve the incorporation of ADM with the recipient, with improved patient outcomes.


Modern slavery in the United Kingdom: The illegal migration act risks undermining efforts to combat exploitation.
The Illegal Migration Act, which recently passed through the United Kingdom (UK) parliament, poses a serious threat to the well-being of victims of modern slavery and efforts to combat exploitation. The Act gives the UK Government greater powers to deny support and allow the detention and deportation of potential victims and has been widely criticised, including by medical associations and charities. Measures included in the Act risk perpetuating the deprivation of safety, dignity, and medical care experienced by victims, instead of providing the protections to which they should be entitled.


High intra/interindividual variance ratios for energy and nutrient intakes of pregnant women in rural Malawi show that many days are required to estimate usual intake.
Conventional wisdom suggests that because there is less variety in food intake, fewer days may be needed to capture "usual intake" of individuals in developing countries, but it is also known that intakes may vary considerably across seasons. Because few studies have examined the sources of variation in nutrient intake in subsistence communities, where food availability also may limit day-to-day food choices, our objective was to examine intraindividual and interindividual variability in energy and nutrient intakes in pregnant subsistence farmers in Africa. From 1988 through 1991, we collected a total of 1061 diet days (mean = 6; range; 2-12 d/woman), using the direct food weighing method, from 184 pregnant women in a farming community west of Lilongwe City, Malawi. Two or four consecutive days were collected for each of several visits during the 2nd and 3rd trimesters. Variance ratios were calculated as the error variance/variance across individuals. We found major seasonal differences in energy and nutrient intakes with greater intakes in the harvest than in the preharvest seasons. Adjustment for season and stage of pregnancy did not reduce variance ratios. To estimate true individual intakes within an error range of +/- 20% required 8-23 d for energy, protein, carbohydrates and fiber; and 95-213 d for micronutrients. Thus, despite limited dietary diversity, large within-person variation in nutrient intake demonstrated that more, rather than fewer days of dietary intake were required to correctly identify usual intake in subsistence farmers compared with previous reports for urbanized or Western populations.


Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus.
The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.


Sweet taste preference is associated with greater hypothalamic response to glucose and longitudinal weight gain.
The hypothalamus has an abundant expression of sweet taste receptors that play a role in glucose sensing and energy homeostasis. Evidence suggests that liking "sweets" can be associated with weight gain, but the relationship between sweet taste preference and hypothalamic regulation of appetite is unknown. This study tested the hypothesis that sweet taste preference is associated with increased hypothalamic activation in response to glucose (a purported neural marker for weight gain risk) and greater longitudinal increases in body mass index (BMI). Fifty-four adults aged 18-35 years with a mean (± SD) BMI of 27.99 ± 5.32 kg/m2 completed the study. Height and weight were measured at baseline and 6-12 months later in a subset of 36 participants. Sweet taste preference was assessed via the Monell 2-series, forced-choice tracking procedure. Arterial spin labeling magnetic resonance imaging was performed before and after oral glucose ingestion to determine hypothalamic blood flow response to glucose. Linear models were used to examine relationships between sweet taste preference and the hypothalamic response to glucose and longitudinal changes in BMI, adjusting for age, sex, and baseline BMI. Sweet taste preference was positively associated with glucose-linked hypothalamic blood flow (beta = 0.017, p = 0.043), adjusted for age, sex and BMI. We also observed a positive association between sweet taste preference and longitudinal change in BMI (beta = 0.088, p = 0.015), adjusted for age, sex and baseline BMI. These findings suggest that heightened sweet taste preference is associated with glucose-linked hypothalamic activation and may be linked to increased susceptibility for weight gain.


Digital self-management interventions for osteoarthritis: a systematic scoping review of intervention characteristics, adherence and attrition.
Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates < 20%, with contact and support from researchers not appearing to influence adherence or attrition. Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence.


Metabolic effects of Foofoo corn on healthy volunteers: influence of some traditional Cameroonian sauces.
Little data to guide diet prescription exists about the foods most frequently consumed in Africa. Moreover, the sauce accompanying a meal can significantly alter the metabolic effects of food. Our work was to study the influence of sauces on the metabolic effects of foofoo corn (Zea mays), one of the most commonly consumed foods in several countries in sub-Saharan Africa with a wide range of sauces. Our study population consisted of ten healthy volunteers (five men, five women), aged from 21 to 28 years, with mean BMI of 23.9 (SD 1.9) kg/m2. The study involved seven visits of three hours each, conducted every 2 days, including one devoted to the oral glucose tolerance test (OGTT) and six visits to the consumption of each of 6 meals tested, standardized to 75 g of carbohydrate intake. Blood samples were collected at 0, 15, 30, 60, 90, 120 and 180 min after consumption of meals for blood glucose and triglycerides levels. The glucose area under the curve of each tested meal, was used to calculate its glycemic index, using the OGTT as the reference. The accompanying sauces tested with foofoo corn were: okra sauce (Abelmoschus esculentus), the so-called yellow sauce (Elaeis guinensis), the pistachio sauce (Pistacia vera), the nkui (Triumpheta pentandra), ndolé (Vernonia amygdalima) and cabbage (Brassica oleracea). All meals had generally a low glycemic index, with a maximum of 22.59 % for okra and cabbage, followed by ndolè (20.18 %), the yellow sauce (13.10 %), pistachio sauce (11.60 %), and nkui (5.27 %). There was a difference in the effects of the diets on triglyceride levels only at 180 min (p = 0.03). Whatever the accompanying sauce, foofoo corn has a low glycemic index. Some sauces, such as nkui give it a very low glycemic index and may be of great interest in diet prescription for patients with various metabolic disorders such as diabetes and obesity.


ICE Regimen for Relapsed/Refractory Bone and Soft Tissue Sarcomas in Children.
The outcome of bone and soft tissue sarcomas (BST) after relapse has very poor prognosis with survival rates less than 39%. Unfortunately there are not many treatment options, but promising responses have been reported with ifosfamide, etoposide and carboplatin (ICE). Therefore, we planned a study for children with recurrent/refractory BST treated with ICE regimen to evaluate their demographic features, responses to treatment and outcome. Patients with primary diagnosis of BST and treated with ICE regimen at the time of first or subsequent relapse, progression or unresponsive disease were selected for study. The files were retrospectively evaluated. Thirty of sixty-six patients had metastatic disease at relapse. Patients received median 5 cycles of ICE and were followed-up median 16.3 months. Overall survival rates were 83% and 62% at 1st and 2nd year. The ORR to the regimen was 43%. Survival rates were significantly higher in good responders (3-year EFS and OS rates: 50% vs. 8% and 78% vs. 14%; p<0.0001 and p<0.0001). Survival rates for non-metastatic disease were 42% and 75% for EFS and OS and higher than patients with metastases at relapse (p<0.001 and p<0.0001). EFS and OS rates of patients with rhabdomyosarcoma were 42% and 69%. No grade 3 or 4 renal toxicity was documented. ICE combination improves the outcome of relapsed or refractory sarcomas and it might serve as second line treatment. Patients with no metastases at relapse would benefit more than others with metastatic disease.


Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.
The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.


A prospective study on some immunological changes occurring in the first year of grass pollen desensitization.
Some immunological parameters were followed up during the first year of grass pollen desensitization in 15 patients. The skin reactions with grass pollen extract in a series of tenfold dilutions were diminished in all patients during treatment. In nearly all patients a distinct increase in blocking antibody titre was seen. Serum reagin titres as measured by RAST remained constant or decreased somewhat during desensitization. No significant correlations between all three parameters could be demonstrated.


Breastfeeding in the industrialized world. Review of the literature.
Since the Industrial Revolution there has been an almost continuous decline in breastfeeding in North-America and western Europe. But the last years numerous studies report that breastfeeding is regaining popularity. The social forces responsible for this are a back-to-nature movement, ecological concerns, breastfeeding support groups and a renewed interest by scientists, the health profession and national and international organizations. Many determinants of child feeding behaviour have been analyzed extensively: ethnic and cultural background, socioeconomic and employment status, maternal (age, parity, marital status) and child (sex, birthweight) characteristics, maternal knowledge and attitudes, health care management. Still the relative influence of these factors can only be estimated, partly because of a lack of an accurate methodology. The reasons mentioned with regard to weaning often indicate a lack of confidence intensified by deficiencies in information and support systems. The negative influence of the infant food industry on breastfeeding behaviour cannot be disregarded. Clearly the promotion of breastfeeding in our society is a policy matter, requiring positive action in the field of health education; legislation, research and the reorganization of health services.


The Mini Nutritional Assessment as an assessment tool in elders in long-term care.
The prevalence of malnutrition increases with age and is most common in the institutionalized individual. Malnutrition is a condition associated with greater susceptibility to infection, longer hospital stay, and increased mortality. Detection of risk of malnutrition in elders and early intervention may lessen these negative consequences. A tool that has been used for assessing nutritional status of elders is the Mini Nutritional Assessment, or MNA. The MNA tool was originally validated in relatively healthy elders in France and New Mexico, but assessment scores seem to correlate with immune function, morbidity, and mortality of elders in long-term care. One of the advantages of using the MNA for assessing nutritional status of elders in long-term care is that it does not need any biochemical tests, such as serum albumin or prealbumin. A weakness of the MNA is that a number of questions target independent-living elders but not elders in long-term care or elders receiving nutrition support. The benefits, limitations, and interpretations in the use of this tool in a long-term care setting are discussed.


Co(I)-Catalyzed [3 + 2] Annulation of o-Haloaryl Imines with Alkenes for the Synthesis of Indanamines.
The use of a CoBr2/1,10-phenanthroline catalytic system together with Zn as the reductant was developed to prepare diversely substituted indanamines by a Co(I)-catalyzed [3 + 2] annulation of o-haloaryl imines with electron-deficient alkenes in good yields. The use of Mn as the reductant allowed the elaboration of a three-component version of this reaction. These conditions were also found to be suitable for the activation of various halides and were extended to the preparation of the indenamine and strigolactam scaffolds.


TNF-alpha induction of A1 expression in human cancer cells.
A1, a member of the Bcl-2 gene family, was originally identified as a hemopoietic-specific early response gene. Later it was found that A1 was overexpressed in human stomach cancer tissues and was induced by tumor necrosis factor-alpha (TNF-alpha) in human vascular endothelial cells. However, its expression in human cancer cells has not been well characterized. In the present study, we examined the expression of A1, as well as the antioxidant manganous superoxide dismutase (MnSOD), in four human thyroid carcinoma cell lines, two human pancreatic carcinoma cell lines, and two human prostate carcinoma cell lines. A1 mRNA was expressed in all four thyroid carcinoma cell lines. TNF-alpha induced A1 in a time- and dose-dependent manner. In contrast, A1 mRNA was not detectable in the pancreatic and prostate carcinoma cell lines in the presence or absence of TNF-alpha. However, TNF-alpha induced manganous superoxide dismutase (MnSOD) mRNA in all the cell lines tested. Furthermore, an agonist antibody to the p55 TNF-alpha receptor induced A1, but the agonist antibody against p75 TNF-alpha receptor did not have this effect. The results indicate that A1 is expressed in human thyroid carcinoma cells and TNF-alpha induces A1 through the p55 TNF-alpha receptor-mediated pathway.


Neither alpha-synuclein-preformed fibrils derived from patients with GBA1 mutations nor the host murine genotype significantly influence seeding efficacy in the mouse olfactory bulb.
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive motor symptoms and alpha-synuclein (αsyn) aggregation in the nervous system. For unclear reasons, PD patients with certain GBA mutations (GBA-PD) have a more aggressive clinical progression. Two testable hypotheses that can potentially account for this phenomenon are that GBA1 mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains). We tested these hypotheses by treating homozygous GBA1 D409V knockin (KI) mice with human α-syn-preformed fibrils (PFFs) and treating wild-type mice (WT) with several αsyn-PFF polymorphs amplified from brain autopsy samples collected from patients with idiopathic PD and GBA-PD patients with either homozygous or heterozygous GBA1 mutations. Robust phosphorylated-αsyn (PSER129) positive pathology was observed at the injection site (i.e., the olfactory bulb granular layer) and throughout the brain six months following PFF injection. The PFF seeding efficiency and degree of spread were similar regardless of the mouse genotype or PFF polymorphs. We found that PFFs amplified from the human brain, regardless of patient genotype, were generally more effective seeders than wholly synthetic PFFs (i.e., non-amplified); however, PFF concentration differed between these two studies, and this might also account for the observed differences. To investigate whether the molecular composition of pathology differed between different seeding conditions, we permed Biotinylation by Antibody Recognition on PSER129 (BAR-PSER129). We found that for BAR-PSER129, the endogenous PSER129 pool dominated identified interactions, and thus, very few potential interactions were explicitly identified for seeded pathology. However, we found Dctn2 interaction was shared across all PFF conditions, and Nckap1 and Ap3b2 were unique to PFFs amplified from GBA-PD brains of heterozygous mutation carriers. In conclusion, both the genotype and αsyn strain had little effect on overall seeding efficacy and global PSER129-interactions.


Outcomes of arthroscopic Hill-Sachs remplissage and anterior Bankart repair: a retrospective controlled study including ultrasound evaluation of posterior capsulotenodesis and infraspinatus strength assessment.
Hill-Sachs lesions are compression fractures that result from shoulder dislocation. They involve "engaging" the humeral head on the anterior glenoid rim when the arm is abducted and externally rotated. The defect grows as the number of dislocations increases. Arthroscopic remplissage and anterior Bankart repair do not significantly affect infraspinatus strength while ensuring healing of the capsulotenodesis. Cohort study; Level of evidence, 3. Sixty-one patients with traumatic anterior shoulder instability treated by arthroscopic Bankart repair and Hill-Sachs remplissage at least 24 months previously were compared with a control group of 40 healthy participants. Preoperative imaging included magnetic resonance imaging for Bankart lesion identification and computed tomography to quantify the humeral head defect. Active range of motion and clinical scores (Walch-Duplay, Constant-Murley, and Rowe) were assessed. External rotation (ER) and internal rotation (IR) were measured with arm at the side (ER1 and IR1) and abducted at 90° (ER2 and IR2). Infraspinatus strength was assessed with the scapula free (infraspinatus strength test [IST]) and retracted (infraspinatus scapula retraction test [ISRT]). Infraspinatus tenodesis and posterior capsulodesis healing were evaluated by ultrasound (US). The follow-up median was 39.5 months (range, 24-56 months). One patient experienced a recurrence of instability at 34 months. In the remplissage patients, ER1 was significantly lower in the affected compared with the unaffected shoulder (P < .001). Mean IST and ISRT strength values did not show differences between sides. The mean Constant-Murley score rose from 62.9 ± 7.1 to 90 ± 5.2 (P < .0001). The Walch-Duplay and Rowe scores were excellent in 23 (78.6%), good in 6 (17.8%), and poor in 1 patient (both scores). The remplissage group had significantly lower ER1 (P < .001), ER2 (P < .001), and IR2 (P < .01) values compared with the control group. Differences in IST and ISRT between the groups were not significant. Capsulotenodesis healing and filling of the Hill-Sachs defect were confirmed by dynamic US in all subjects. Arthroscopic remplissage is a reliable approach to Hill-Sachs lesions. The ER and IR restriction does not significantly affect quality of life. Infraspinatus strength recovery is satisfactory even compared with healthy subjects. Ultrasound examination allows accurate evaluation of capsulotenodesis healing.


The Complexities of Categorizing Gender: A Hierarchical Clustering Analysis of Data from the First Australian Trans and Gender Diverse Sexual Health Survey.
Purpose: This study used self-reported gender among trans and gender diverse people in Australia to identify and describe broad, overarching gender categories that encompass the expansive ways in which gender can be defined and expressed. Methods: Data were collected as part of the Australian Trans and Gender Diverse Sexual Health Survey hosted in October 2018. Participant self-identification with nonexclusive gender categories were analyzed using algorithm-based hierarchical clustering; factors associated with gender clusters were identified using logistic regression analyses. Results: Usable data were collected from 1613 trans and gender diverse people in Australia, of whom 71.0% used two or more labels to describe their gender. Three nonexclusive clusters were identified: (i) women/trans women, (ii) men/trans men, and (iii) nonbinary. In total, 33.8% of participants defined their gender in exclusively binary terms (i.e., men/women, trans men/trans women), 40.1% in nonbinary terms, and 26.0% in both binary and nonbinary terms. The following factors were associated with selecting nonbinary versus binary gender labels: presumed female gender at birth (adjusted odds ratio [aOR]=2.02, 95% confidence interval [CI]=1.60-2.54, p<0.001), having a majority of sexual and/or gender minority friends (aOR=2.46, 95% CI=1.49-3.10, p<0.001), and having spent more than half of one's life identifying as trans and/or gender diverse (aOR=1.75, 95% CI=1.37-2.23, p<0.001). Conclusion: Trans and gender diverse people take up diverse and often multiple gender labels, which can be broadly categorized as binary and nonbinary. Systems of health care and research must be adapted to include nonbinary people while remaining amenable to further adaptation.


Recent Advances in the Prevention and Management of Monkeypox Viral Infection in Humans.
There have been several neglected infectious pathogens that have reemerged in the last few decades, including the monkeypox virus, a virus from the orthopoxviral genus that causes monkeypox and is transmitted between animals and humans. The human monkeypox outbreak has spread to several different countries. Because of the outbreak's unusually high case count and lack of connections to endemic nations, there are concerns that the monkeypox transmission pattern may have changed. The current study aimed to provide recent advancements in the prevention and management of the monkeypox virus in humans. We have highlighted recent advancements in the prevention and management of the monkeypox virus in humans in this work. For the treatment and prevention of monkeypox, new medications and vaccinations are being used, and more study is needed to understand the epidemiology, biology, and ecology of the virus in endemic regions and stop future global outbreaks. Vaccines available in the market for the treatment of viruses are JYNEOS and ACAM2000. Some of the antiviral drugs, such as tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin, are used for the treatment of the monkeypox virus. Some of the vaccines, such as NIOCH-14, Cidofovir, CMX-001, and ST-246, are currently in clinical trials. We have, herein, covered features of monkeypox viral biology that are important for risk assessment and getting ready for an outbreak of the monkeypox virus, with a focus on recent advances in knowledge of the virus's host range, evolutionary potential, and potential targets for neutralization.


Organic-soluble antimicrobial silver nanoparticle-polymer composites in gram scale by one-pot synthesis.
We report a one-pot synthesis of silver nanoparticle-polymer composites (Ag-PNCs) in water by a novel finding involving the polycondensation of methoxybenzyl chlorides (MeO-BzCl) directly on Ag nanoparticle surfaces at room temperature, leading to highly soluble antimicrobial nanocomposites. The composites, which are soluble in a range of organic solvents, precipitate in the reaction vessel, making their separation simple. Solutions of the composites can be casted directly on substrates or made into freestanding films. The material was found to be stable for nearly 2 years. A range of substrates have been shown to become antibacterial by direct application of this material. The experiments were conducted with Ag-PNC-loaded filter paper strips and glass substrates. The samples were found to be antimicrobial (against Escerichia coli and Aspergillus niger). The simple one-pot approach of this kind to make organic-soluble antibacterial coatings could have wide implications.


Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion.
It has been proposed that glutamatergic and dopaminergic systems are functionally opposed in their regulation of striatal output. The present study tested the effects of drugs that enhance AMPA-receptor-mediated glutamatergic transmission (ampakines) for their effects on dopamine-related alterations in cortical activity and locomotor behavior. Rats with unilateral 6-hydroxydopamine lesions of the ascending nigro-striatal dopamine system were sensitized to methamphetamine and then tested for methamphetamine-induced circling behavior in the presence and absence of ampakines CX546 and CX614. Both ampakines produced rapid, dose-dependent reductions in circling that were evident within 15 min and sustained through 1 h of behavioral testing. In situ hybridization maps of c-fos mRNA expression showed that in the intact hemisphere, ampakine cotreatment markedly increased c-fos expression in parietal, sensori-motor neocortex above that found in rats treated with methamphetamine alone. Ampakine cotreatment did not augment c-fos expression in frontal, sensori-motor cortex or striatum. Still larger ampakine-elicited effects were obtained in parietal cortex of the dopamine-depleted hemisphere where labeling densities were increased by approximately 60% above values found in methamphetamine-alone rats. With these effects, the hemispheric asymmetry of cortical activation was less pronounced in the ampakine-cotreatment group as compared with the methamphetamine-alone group. These results indicate that positive modulation of AMPA-type glutamate receptors 1) can offset behavioral disturbances arising from sensitized dopamine receptors and 2) increases aggregate neuronal activity in a regionally selective manner that is probably dependent upon behavioral demands.


[Morbidity of transperineal echo-guided prostatic biopsy, our experience].
We present a review of 1245 patients undergone to ultrasound guided transperineal prostatic biopsy. We examined the complications' incidence of this technique to confirm or exclude presence of prostate cancer. Indications to a prostatic biopsy include an abnormal digital rectal examination, TRUS or PSA values increased. Single biopsy or systematic mapping of prostate were performed. For prostate biopsy a "Biopsy Gun" with 18 G. needle was used. Of 1245 patients, only 31 (2.48%) showed complications. Our experience demonstrates that ultrasound guided transperineal prostatic biopsy is a safe and easy technique and it is well accepted by the patient.


[Elevation of serum apo E-rich HDL concentration in a patient with cholestatic liver disease].
A remarkable elevation of serum HDL cholesterol concentration (165mg/dl) was found in a 42-year-old Japanese male with chronic pancreatitis who had been cholestatic for several years. An abnormal slow alpha-migrating lipoprotein, larger in particle size and more enriched with cholesteryl ester and apo E than normal HDL, was found in the patient's plasma. Quantitative determination of apo E-rich HDL revealed a striking increase of this lipoprotein in plasma. After choledocho-jejunostomy, a prompt and remarkable decrease of plasma apo E-rich HDL was observed, indicating a direct contribution of cholestasis to the accumulation of apo E-rich HDL in plasma in this patient.


Temporal Behavioral Parameters of On-Going Gaze Encounters in a Virtual Environment.
To navigate the social world, humans heavily rely on gaze for non-verbal communication as it conveys information in a highly dynamic and complex, yet concise manner: For instance, humans utilize gaze effortlessly to direct and infer the attention of a possible interaction partner. Many traditional paradigms in social gaze research though rely on static ways of assessing gaze interaction, e.g., by using images or prerecorded videos as stimulus material. Emerging gaze contingent paradigms, in which algorithmically controlled virtual characters can respond flexibly to the gaze behavior of humans, provide high ecological validity. Ideally, these are based on models of human behavior which allow for precise, parameterized characterization of behavior, and should include variable interactive settings and different communicative states of the interacting agents. The present study provides a complete definition and empirical description of a behavioral parameter space of human gaze behavior in extended gaze encounters. To this end, we (i) modeled a shared 2D virtual environment on a computer screen in which a human could interact via gaze with an agent and simultaneously presented objects to create instances of joint attention and (ii) determined quantitatively the free model parameters (temporal and probabilistic) of behavior within this environment to provide a first complete, detailed description of the behavioral parameter space governing joint attention. This knowledge is essential to enable the modeling of interacting agents with a high degree of ecological validity, be it for cognitive studies or applications in human-robot interaction.


Antihepatoma activity of chaetocin due to deregulated splicing of hypoxia-inducible factor 1α pre-mRNA in mice and in vitro.
Chaetocin, an antibiotic produced by Chaetomium species fungi, was recently found to have antimyeloma activity. Here we examined whether chaetocin has anticancer activities against solid tumors. Chaetocin inhibited the growth of mouse and human hepatoma grafts in nude mice. Immunohistochemical analyses revealed that chaetocin inhibits hypoxia-inducible factor-1α (HIF-1α) expression and vessel formation in the tumors. Chaetocin also showed antiangiogenic anticancer activities in HIF-1α(+/+) fibrosarcoma grafted in mice, but not in HIF-1α(-/-) fibrosarcoma. Biochemical analyses showed that chaetocin down-regulated HIF-1α and the transcripts of HIF-1 target genes including vascular endothelial growth factor in hepatoma tissues and in various hepatoma cell lines. Based on the reported literature, unsuccessful efforts were made to determine the mechanism underlying the action of chaetocin. Unexpectedly, chaetocin was found to cause the accumulation of HIF-1α premessenger RNA (pre-mRNA) but to reduce mature mRNA levels in hepatoma cells and tissues. Such an effect of chaetocin was not observed in cell lines derived from normal cells, and was cell type-dependent even among cancer cell lines. Our results suggest that chaetocin could be developed as an anticancer agent to target HIF-1 in some cancers including hepatoma. It is also suggested that the HIF-1α pre-mRNA splicing is a novel therapeutic target for controlling HIF-1-mediated pathological processes.


Nitric oxide and the vascular endothelium.
The vascular endothelium synthesises the vasodilator and anti-aggregatory mediator nitric oxide (NO) from L-arginine. This action is catalysed by the action of NO synthases, of which two forms are present in the endothelium. Endothelial (e)NOS is highly regulated, constitutively active and generates NO in response to shear stress and other physiological stimuli. Inducible (i)NOS is expressed in response to immunological stimuli, is transcriptionally regulated and, once activated, generates large amounts of NO that contribute to pathological conditions. The physiological actions of NO include the regulation of vascular tone and blood pressure, prevention of platelet aggregation and inhibition of vascular smooth muscle proliferation. Many of these actions are a result of the activation by NO of the soluble guanylate cyclase and consequent generation of cyclic guanosine monophosphate (cGMP). An additional target of NO is the cytochrome c oxidase, the terminal enzyme in the electron transport chain, which is inhibited by NO in a manner that is reversible and competitive with oxygen. The consequent reduction of cytochrome c oxidase leads to the release of superoxide anion. This may be an NO-regulated cell signalling system which, under certain circumstances, may lead to the formation of the powerful oxidant species, peroxynitrite, that is associated with a variety of vascular diseases.


A new lens for observing fundus with a noncontact wide-angle viewing system.
Drying of the cornea during surgery, which causes poor visibility of the fundus, is one of the most serious problems when using a noncontact-type wide-angle viewing system. This study used a newly commercialized lens for observing the fundus with a noncontact wide-angle viewing system. The lens used has a very thin meniscus made of polymethyl methacrylate and a large outer diameter. Following the application of viscoelastic material, the lens can be put on the cornea without using a contact lens fixation ring. The larger diameter and lightweight characteristics of the new lens contributed to the overall stabilization. The smooth surface of this lens was able to achieve an intraoperative view of good quality not only during vitrectomy but also during scleral buckling procedures.


Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-naïve Korean patients infected with genotype C2.
To report naturally occurring mutations in the reverse transcriptase region (RT) of hepatitis B virus (HBV) polymerase from treatment naïve Korean chronic patients infected with genotype C2. Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment naïve Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis (CH) and 72 patients with hepatocellular carcinoma (HCC). The deduced amino acids (AAs) at 42 previously reported potential nucleos(t)ide analog resistance (NAr) mutation positions in the RT region were analyzed. Potential NAr mutations involving 24 positions were found in 79 of the 131 patients (60.3%). Notably, AA substitutions at 2 positions (rt184 and rt204) involved in primary drug resistance and at 2 positions (rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients (1 CH patient and 9 HCC patients) and 7 patients (1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients (3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients (2.09%, 52/2478 mutations) (P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment naïve Korean patients. Our data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression (particularly HCC generation) in chronic patients with genotype C2 infections.


Photoswitchable Chiral Cation-Binding Catalyst: Photocontrol of Catalytic Activity on Enantioselective Aminal Synthesis.
Design of a suitable photoswitchable chiral cation-binding cage for the synthesis of optically active aminals was established using the azobenzene-BINOL hybrid oligoethylene glycol (ABOEG) through E/Z isomerization of the azobenzene unit. Under photoirradiation, both the catalytic activity and enantioselectivity of the generating (Z)-ABOEG are enhanced, in contrast to that of (E)-ABOEG, which can be attributed to the geometrically distinct coordination behavior between the metal cation and the oligoethylene glycols.