Cost effectiveness analysis of implementing tuberculosis screening among applicants for non-immigrant U.S. work visas.
While persons who receive immigrant and refugee visas are screened for active tuberculosis before admission into the United States, nonimmigrant visa applicants (NIVs) are not routinely screened and may enter the United States with infectious tuberculosis. We evaluated the costs and benefits of expanding pre-departure tuberculosis screening requirements to a subset of NIVs who arrive from a moderate (Mexico) or high (India) incidence tuberculosis country with temporary work visas. We developed a decision tree model to evaluate the program costs and estimate the numbers of active tuberculosis cases that may be diagnosed in the United States in two scenarios: 1) "Screening": screening and treatment for tuberculosis among NIVs in their home country with recommended U.S. follow-up for NIVs at elevated risk of active tuberculosis; and, 2) "No Screening" in their home country so that cases would be diagnosed passively and treatment occurs after entry into the United States. Costs were assessed from multiple perspectives, including multinational and U.S.-only perspectives. Under "Screening" versus "No Screening", an estimated 179 active tuberculosis cases and 119 hospitalizations would be averted in the United States annually via predeparture treatment. From the U.S.-only perspective, this program would result in annual net cost savings of about $3.75 million. However, rom the multinational perspective, the screening program would cost $151,388 per U.S. case averted for Indian NIVs and $221,088 per U.S. case averted for Mexican NIVs. From the U.S.-only perspective, the screening program would result in substantial cost savings in the form of reduced treatment and hospitalization costs. NIVs would incur increased pre-departure screening and treatment costs.


Mother-infant interaction; effects of sex of infant on feeding behaviour.
Mother--child interaction was studied on the 2nd and 4th days after delivery. Mothers with girls showed more distal contact behaviour such as talking, smiling, and 'en face' responses. They also displayed more skin-to-skin contact behaviour (patting, rubbing, kissing, and touching) toward girl babies. Mothers with boys, on the other hand, showed more types of behaviours directed to clothed parts of the infant such as patting and adjusting clothes. These findings were statistically significant only on the 2nd day after delivery. On day 4 differences between male and female infants both in the frequency and in the pattern of sucking were observed.


Effect of High Postoperative Body Temperature on Long-Term Prognosis in Patients with Gastric Cancer After Radical Resection.
There is a lack of data on the effect of high postoperative body temperature on disease-free survival (DFS) in patients who underwent radical gastrectomy. Patients who underwent radical gastrectomy from January 2006 to December 2011 were selected. The highest body temperature within 1 week after operation was used to establish diagnostic thresholds for high and low body temperature through X-tile software. A total of 1396 patients were included in the analysis. The diagnostic threshold for high body temperature was defined as 38 °C; 370 patients were allocated to the high-temperature group (HTG), while another 1026 patients were allocated to the low-temperature group (LTG). For all patients, survival analysis showed that 5-year DFS in the HTG was significantly lower than that for the LTG (55.6% vs 63.9%, P = 0.007). Multivariate analysis revealed that high postoperative body temperature was an independent prognostic risk factor for 5-year DFS (HR = 1.288 (1.067-1.555), P = 0.008). For patients without complications, survival analysis showed that the 5-year DFS rate in the HTG was lower than that for the LTG (57.5% vs 64.4%, P = 0.051), especially in patients with stage III gastric cancer (31.3% vs 41.7%, P = 0.037). For patients with complications or infectious complications, there were no significant differences between the HTG and LTG regarding 5-year DFS (49.3% vs 58.2%, P = 0.23 and 49.4% vs 55.1%, P = 0.481, respectively). For stage III gastric cancer patients without complications, high postoperative body temperature can significantly reduce the 5-year DFS. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.


OsGLYI3, a glyoxalase gene expressed in rice seed, contributes to seed longevity and salt stress tolerance.
The glyoxalase pathway plays a vital role in the chemical detoxification of methylglyoxal (MG) in biological systems. Our previous study suggested that OsGLYI3 may be effective in seed natural aging. In this study, the rice OsGLYI3 gene was cloned and characterized as specifically expressed in the seed. The accelerated aging (AA) treatment results indicated significant roles of OsGLYI3 in seed longevity and vigor, as the seeds of the transgenic lines with overexpressed and knocked-out OsGLYI3 exhibited higher and lower germination, respectively. The AA treatment also increased the superoxide dismutase (SOD) activity in the overexpressed transgenic seeds compared to the wild-type seeds yet lowered the SOD activity in the CRISPR/Cas9-derived transgenic rice lines. Rice OsGLYI3 was markedly upregulated in response to NaCl induced stress conditions. Compared to wild-type plants, overexpressed transgenic rice lines exhibited increased GLYI activity, decreased MG levels and improved salt stress tolerance, while CRISPR/Cas9 knockout transgenic rice lines showed decreased glyoxalase I activity, increased MG levels, and greater sensitivity to stress treatments with NaCl. Collectively, our results confirmed for the first time that OsGLYI3 is specifically expressed in rice seeds and contributes to seed longevity and salt stress tolerance.


Dual-stream modulation failure: a novel hypothesis for the formation and maintenance of delusions in schizophrenia.
Delusions, a cardinal feature of schizophrenia, are characterized by the development and preservation of false beliefs despite reason and evidence to the contrary. A number of cognitive models have made important contributions to our understanding of delusions, though it remains unclear which core cognitive processes are malfunctioning to enable individuals with delusions to form and maintain erroneous beliefs. We propose a modified dual-stream processing model that provides a viable and testable mechanism that can account for this debilitating symptom. Dual-stream models divide decision-making into two streams: a fast, intuitive and automatic form of processing (Stream 1); and a slower, conscious and deliberative process (Stream 2). Our novel model proposes two key influences on the way these streams interact in everyday decision-making: conflict and emotion. Conflict: in most decision-making scenarios one obvious answer presents itself and the two streams converge onto the same conclusion. However, in instances where there are competing alternative possibilities, an individual often experiences dissonance, or a sense of conflict. The detection of this conflict biases processing towards the more deliberative Stream 2. Emotion: highly emotional states can result in behavior that is reflexive and action-oriented. This may be due to the power of emotionally valenced stimuli to bias reasoning towards Stream 1. We propose that in schizophrenia, an abnormal response to these two influences results in a pathological schism between Stream 1 and Stream 2, enabling erroneous intuitive explanations to coexist with contrary logical explanations of the same event. Specifically, we suggest that delusions are the result of a failure to reconcile the two streams due to both a failure of conflict to bias decision-making towards Stream 2 and an accentuated emotional bias towards Stream 1.


Rising and Falling High-Sensitivity Cardiac Troponin in Diagnostic Algorithms for Patients With Suspected Myocardial Infarction.
Background High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.


Tetraplegia Hand Activity Questionnaire (THAQ): the development, assessment of arm-hand function-related activities in tetraplegic patients with a spinal cord injury.
Development of Tetraplegia Hand Activity Questionnaire (THAQ). Patients and spinal cord injury (SCI) professionals from five rehabilitation centres in the Netherlands and Belgium. To construct a disease-specific questionnaire to evaluate interventions to the arm-hand of tetraplegics in terms of gained and lost activities relevant to the patient. All arm-hand function-related activities were inventoried by examining existing scales and interviewing spinal cord injury patients and professionals in the field. Subsequently, item reduction was achieved; first, in the technical construction by incorporating all activities in an item list, then reducing the list by selecting the items most likely to be sensitive to change after surgical or functional electro stimulation interventions on the arm-hand as judged by an expert panel, using a Delphi method. The arm-hand-related activity inventory comprised 652 activities. The technical construction of the items and the Delphi procedure resulted in a questionnaire with 153 items. The experts considered many of the 'new' activities more relevant for the evaluation of hand function interventions than those found in scales studied in the literature. This is reflected in a relatively large proportion of new activities (69%) for the item list of the THAQ, and even more in the domains work/admin/telecom (88%) and leisure (100%). The questionnaire constructed to assess hand function-related activities contains relevant activities to evaluate arm-hand function-related interventions for tetraplegic SCI patients.


Impact of vanilla origins on sensory characteristics of chocolate.
The sensory characteristics of white and milk chocolate with three origins of vanilla (Madagascar, Indonesia, Papua New Guinea) were investigated using a multi-analytical approach. The sensory tests included profiling using Quantitative Descriptive Analysis with a trained panel; Temporal Dominance of Sensations test with untrained respondents from various countries currently residing in Belgium, and the consumers sensory preference test with consumers in Belgium, France, Sweden and Canada. The vanilla extracts were also analyzed by gas chromatography-mass spectrometry (GC-MS) in combination with olfactometry (GC-MS-O) to identify the key aroma compounds in the different vanilla origins. This research shows that sensory profile of Papua New Guinea (PNG) samples is different from Madagascan and Indonesian extracts. The flavor signature was correlated with almondy and anisic descriptors. The perceived difference between Madagascan and Indonesian origins was reduced when assessed within complex matrices such as chocolate. In sugared water, Madagascan vanilla has balsamic, phenolic notes while Indonesian has woodier notes. In a chocolate base, the Indonesian sample lost its woody characteristic for a dairy enhanced characteristic. The botanical variety has more impact on difference in sensory profile of a chocolate than the vanilla origin itself. The sensory data correlates with volatile components identified in this study. Guaiacol and vanillin were identified as the main key aroma compounds in all three vanilla origins using GC-MS-O. Additional key aroma compounds were responsible for the differences in sensory characteristics between the three vanilla origins: anisaldehyde for anisic note in the PNG samples and ethyl 2-methylbutanoate and 3/2-methylbutanoic acid in the Indonesian sample. Sensory profiles of vanillas from various origins were more visible and pronounced in white chocolate compared to milk chocolate. This study gives novel insights to the chocolate, as well as the vanilla sectors, indicating possibilities of vanilla replacement and consumer preferences across Europe and Canada. The consumer study shows that, on average, people do not indicate which chocolate is significantly more liked.


Factors Influencing the Outcome of Spontaneous Healing of Traumatic Tympanic Membrane Perforation: A Clinical Prospective Observational Study.
Trauma to the ear is typically attributed to its location in the craniofacial skeleton. TM is prone to rupture, tear, or perforation when traumatized. Etiological factors may be classified according to the pathogenetic mechanisms (air-pressure change, heat, solids, water pressure). This is a prospective study of 70 patients with traumatic tympanic membrane perforation between January 2019 and December 2022. Inclusion and exclusion criteria applied and results interpreted. Traumatic TM affects all age groups with a mean age of 27.94 ± 4.76 years. Traumatic TM affects all age groups with a mean age of 27.94 ± 4.76 years, with the highest incidence among the middle-aged groups 61.4%. The male-to-female ratio was found to be 1.9:1, with high predominance among male patients (65.7%) with a frequency of 57.1% for slap injury group in our study contrary to others. Spontaneous healing was observed in 88.6% over a follow-up period of 12 weeks in this study. Our study has not shown that associated comorbidities influence healing (P = 0.550). About 45.5% Marginal perforations have not healed in 12 weeks follow-up period as compared to central perforations 5.1%. There is a high predominance of TM perforation among male patients in our study may be attributed to activity. Spontaneous healing is more common. Duration of healing was significantly affected by the size of the perforation with longer duration for large perforations and vice versa. It is observed in this study that the duration of spontaneous healing is longer in blast injuries when compared to other kinds of injuries. A significant proportion of marginal perforations that have not healed in our study may be attributed to annular ligament involvement.


Reproduction of sepsis and endocarditis by experimental infection of chickens with Streptococcus gallinaceus and Enterococcus hirae.
This study describes experimental infections in 4-week-old chickens inoculated intravenously with approximately 10(8) colony-forming units Streptococcus gallinaceus strain CCUG 42692T (C13156) or Enterococcus hirae strain DSM 20160 (C17410). Birds were necropsied following death and obvious clinical signs of disease or were euthanized weekly after infection for up to 4 weeks. At necropsy, lesions included splenomegaly, hepatomegaly, valvular and/or mural endocarditis. Cardiac lesions included focal necrotizing myocarditis and/or yellow-white vegetative valvular endocarditis or greyish proliferations associated with the mitral valves in 35% (6/20) and 79% (19/24) of birds infected with S. gallinaceus and in 20% (4/20) and 55% (12/22) of birds infected with E. hirae via the brachial and jugular veins, respectively. S. gallinaceus was reisolated from heart valves in 45% (9/20) and 75% (18/24) and E. hirae in 35% (7/20) and 73% (16/22) after inoculation via brachial and jugular veins, respectively. Both challenge strains were also isolated from liver, spleen, bone marrow and hock joints. A significant difference between the infections with the two strains was seen only with reisolation of E. hirae from hock joints (P < 0.007). Significant differences were apparent between the two inoculation routes only with E. hirae, where infection via the jugular vein was associated with higher culture positive isolations from the heart (P = 0.029), bone marrow (P = 0.002) and hock joints (P < 0.001) compared with the brachial vein. Birds injected with sterile phosphate-buffered saline were negative for culture of the challenge strains and no lesions were observed in these controls. The results confirm that both S. gallinaceus and E. hirae can cause endocarditis in experimentally infected chickens.


Gaze-independent BCI-spelling using rapid serial visual presentation (RSVP).
A Brain Computer Interface (BCI) speller is a communication device, which can be used by patients suffering from neurodegenerative diseases to select symbols in a computer application. For patients unable to overtly fixate the target symbol, it is crucial to develop a speller independent of gaze shifts. In the present online study, we investigated rapid serial visual presentation (RSVP) as a paradigm for mental typewriting. We investigated the RSVP speller in three conditions, regarding the Stimulus Onset Asynchrony (SOA) and the use of color features. A vocabulary of 30 symbols was presented one-by-one in a pseudo random sequence at the same location of display. All twelve participants were able to successfully operate the RSVP speller. The results show a mean online spelling rate of 1.43 symb/min and a mean symbol selection accuracy of 94.8% in the best condition. We conclude that the RSVP is a promising paradigm for BCI spelling and its performance is competitive with the fastest gaze-independent spellers in literature. The RSVP speller does not require gaze shifts towards different target locations and can be operated by non-spatial visual attention, therefore it can be considered as a valid paradigm in applications with patients for impaired oculo-motor control.


Association between worsening renal function severity during hospitalization and low physical function at discharge: a retrospective cohort study of older patients with heart failure and chronic kidney disease from Japan.
The number of hospitalized older patients with chronic heart failure, chronic kidney disease, and worsening renal function is rising in Japan. This study aimed to clarify the impact of the severity of worsening renal function during hospitalization on low physical function at discharge of these patients. We included 573 consecutive heart failure patients who underwent phase I cardiac rehabilitation. Worsening renal function severity was defined according to elevation during hospitalization of baseline serum creatinine on admission: non-worsening renal function, serum creatinine < 0.2 mg/dL; worsening renal function II/I, serum creatinine ≥ 0.2 to < 0.5 mg/dL; worsening renal function III, and serum creatinine ≥ 0.5 mL/dL. Physical function was measured with the Short Performance Physical Battery. We compared background factors, clinical parameters, pre-hospitalization walking levels, Functional Independence Measure score, and physical function in the three renal function groups. Multiple regression analysis was performed with the Short Performance Physical Battery at discharge as the dependent variable. The final analysis included 196 patients (mean age 82.7 years, male 51.5%) categorized into three groups based on worsening renal function: worsening renal function grade III group (n = 55), worsening renal function grade II/I group (n = 36), and non-worsening renal function group (n = 105). There is no significant difference in walking levels before hospitalization between the three groups, but physical function at discharge was significantly lower in the worsening renal function III group. Moreover, worsening renal function III was an independent factor for low physical function at discharge. Worsening of renal function during hospitalization in older patients with heart failure and chronic kidney disease was strongly associated with low physical function at discharge, even after adjusting for other potentially confounding factors, such as pre-hospitalization walking levels, walking start day, and Geriatric Nutrition Risk Index at discharge. Notably, worsening renal function of mild or moderate severity (grade II/I) did not show a significant association with low physical function.


Lymphoma-induced polyradiculopathy in AIDS: two cases.
Progressive polyradiculopathy is a rare, well-documented complication of the acquired immunodeficiency syndrome in man. It has been commonly attributed to a cytomegalovirus (CMV) infection. We report two HIV-infected patients with clinical and electrophysiological features of a unique, subacute, progressive polyradiculopathy. Post-mortem examination in case 1 disclosed an infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic lymphoma. Immunochemistry for HIV1 and CMV was negative in the peripheral and the central nervous system. Case 2 showed bone-marrow involvement by a Burkitt type lymphoma. Specific chemotherapy was followed by both clinical improvement of the polyradiculopathy and complete remission on a second bone-marrow biopsy. These findings may indicate that a lymphoma must also be considered a possible cause of polyradiculopathy in AIDS.


Biomarkers for rheumatoid and psoriatic arthritis.
Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.


Vocal fold dynamics for frequency change.
This article provides a review of data drawn from a series of related experiments to demonstrate how frequency change (Δf0) is accomplished in the modal register. The research cited involves studies of (1) laryngeal size, (2) vocal fold length, (3) vocal fold thickness, and (4) subglottic pressure; new data describe their effect on vocal fold mass. It was found that changes in these dimensions (1) explain how the shifts in frequency are accomplished, (2) establish the way vocal fold mass can be measured, and (3) strongly support the aerodynamic-myoelastic theory of phonation.


Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study.
The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.


Development and application of a virus-induced gene silencing protocol for the study of gene function in narrow-leafed lupin.
Lupins are promising protein crops with an increasing amount of genomic and transcriptomic resources. The new resources facilitate the in silico identification of candidate genes controlling important agronomic traits. However, a major bottleneck for lupin research and crop improvement is the in planta characterization of gene function. Here, we present an efficient protocol for virus-induced gene silencing (VIGS) to down-regulate endogenous genes in narrow-leafed lupin (NLL) using the apple latent spherical virus (ALSV). We identified ALSV as an appropriate VIGS vector able to infect NLL without causing a discernible phenotype. We created improved ALSV vectors to allow for efficient cloning of gene fragments into the viral genome and for easier viral propagation via agroinfiltration of Nicotiana benthamiana. Using this system, we silenced the visual marker gene phytoene desaturase (PDS), which resulted in systemic, homogenous silencing as indicated by bleaching of newly produced tissues. Furthermore, by silencing lysine decarboxylase (LaLDC)-a gene likely to be involved in toxic alkaloid biosynthesis-we demonstrate the applicability of our VIGS method to silence a target gene alone or alongside PDS in a 'PDS co-silencing' approach. The co-silencing approach allows the visual identification of tissues where silencing is actively occurring, which eases tissue harvesting and downstream analysis, and is useful where the trait under study is not affected by PDS silencing. Silencing LaLDC resulted in a ~ 61% or ~ 67% decrease in transcript level, depending on whether LaLDC was silenced alone or alongside PDS. Overall, the silencing of LaLDC resulted in reduced alkaloid levels, providing direct evidence of its involvement in alkaloid biosynthesis in NLL. We provide a rapid and efficient VIGS method for validating gene function in NLL. This will accelerate the research and improvement of this underutilized crop.


Successful treatment of a child having generalized Kaposi's sarcoma after living donor liver transplantation with conversion to sirolimus.
SRL is a new and potent immunosuppressive agent that has been successfully introduced in organ transplantation. In contrast to other immunosuppressive agents, SRL has a potent antitumor activity both in vitro and in vivo. Herein, we report a child with Kaposi's sarcoma that was diagnosed 30 months after LDLT and treated successfully with only conversion to SRL monotherapy. KS regressed completely at the end of the first month and remained in remission during 28 months follow-up.


Asymmetric retinitis pigmentosa, luetic retinopathy and the question of unilateral retinitis pigmentosa.
A seropositive patient with the fundus appearance of monocular luetic retinopathy is presented. Electrophysiologically, this patient shows a late-onset form of progressive tapetoretinal degeneration (retinitis pigmentosa) presenting in an extremely asymmetric manner. The differential diagnosis of luetic and other inflammatory retinopathies vs. tapetoretinal degenerations is briefly discussed. Features distinguishing unilateral retinitis pigmentosa from bilateral tapetoretinal degenerations are reviewed, and the existence of unilateral retinitis pigmentosa as a genetic entity is questioned. Prolongation of ERG- a- and b-wave implicit times is characteristic of the tapetoretinal degenerations, and normal implicit times in the fellow eye are suggested as an additional criterion for the diagnosis of unilateral retinitis pigmentosa.


Bacillus subtilis sporulation and stationary phase gene expression.
Bacillus subtilis cells entering stationary phase due to nutrient deprivation have a number of options. Complex interconnected regulatory circuits govern differential gene expression patterns that channel the cell along the path it has sensed is most advantageous for survival in the environment. The actual choice depends upon the activity of an elaborate signal transduction network (the phosphorelay) that ultimately affects the activity of two key transcription factors, SpoOA and AbrB. Should the cell commit to sporulation, a temporally and spatially controlled cascade of RNA polymerase sigma factors leads to the development and release of an endospore from within the terminally differentiated, apoptotic mother cell.


An unbiased comparison of organ weights when an inequality in body weight exists.
It is demonstrated in simulations that, if adjustment for inequality in body weight is to be made by covariance analysis and the comparison is carried out in terms of adjusted means of organ weights thus obtained, the test of significance for an organ weight change can be unbiased, or the chances for detecting spurious effects on organ weights remain at about 5% and the chances for detecting treatment effects are far above the 5% irrespective of differences in body weight. Since the use of relative organ weights frequently violates the unbiasedness, it is concluded that if a treated group differs from the control in body weight the comparison of adjusted means of organ weights by covariance analysis will be far more justifiable than that of relative weights.


Metal-organic framework-based hydrogel with structurally dynamic properties as a stimuli-responsive localized drug delivery system for cancer therapy.
Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials, the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.e., self-healing and shear-thinning, as an injectable localized drug delivery platform. The drug-encapsulating MOF hydrogel is formed through a dynamic coordination bond cross-linkage between a doxorubicin-loaded MOF (MOF@DOX) particle and a homemade bisphosphonate-modified hyaluronic acid (HA-BP) polymeric binder. The HA-BP·MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and efficiently kills cancer cells in vitro. The animal experiments reveal that the HA-BP·MOF@DOX hydrogel has enhanced capability in terms of tumor growth suppression as compared to the MOF@DOX group, which can be attributed to drug localization in hydrogel superstructure and sustained release at the tumor site. The presented injectable dynamic MOF-based hydrogel is a promising in vivo localized drug delivery system for cancer treatment. Herein, we report the self-healing and shear-thinning of MOF-based drug carrier cross-linked by coordinate bonds for the first time and provide new insights and a facile chemical strategy for designing and fabricating MOF-based biomaterials by using bisphosphonate-zinc interaction. STATEMENT OF SIGNIFICANCE: Bisphosphonate-zinc interaction is a facile chemical strategy to cross-link metal-organic framework (MOF)-based hydrogel. The presented MOF-based hydrogel demonstrates structurally dynamic properties, including smooth injectability, self-healing, and shear-thinning. The developed MOF-based hydrogel possesses pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The dynamic MOF-based hydrogel shows enhanced in vivo anticancer activity as compared to pure MOF particles. Self-healing and shear-thinning of metal-ligand cross-linked MOF-based drug delivery system are reported for the first time, thus providing new insights for the design and fabrication of MOF-based biomaterials.


The SWI/SNF ATPase BRG1 facilitates multiple pro-tumorigenic gene expression programs in SMARCB1-deficient cancer cells.
Malignant rhabdoid tumor (MRT) is driven by the loss of the SNF5 subunit of the SWI/SNF chromatin remodeling complex and then thought to be maintained by residual SWI/SNF (rSWI/SNF) complexes that remain present in the absence of SNF5. rSWI/SNF subunits colocalize extensively on chromatin with the transcription factor MYC, an oncogene identified as a novel driver of MRT. Currently, the role of rSWI/SNF in modulating MYC activity has neither been delineated nor has a direct link between rSWI/SNF and other oncogenes been uncovered. Here, we expose the connection between rSWI/SNF and oncogenic processes using a well-characterized chemical degrader to deplete the SWI/SNF ATPase, BRG1. Using a combination of gene expression and chromatin accessibility assays we show that rSWI/SNF complexes facilitate MYC target gene expression. We also find that rSWI/SNF maintains open chromatin at sites associated with hallmark cancer genes linked to the AP-1 transcription factor, suggesting that AP-1 may drive oncogenesis in MRT. Interestingly, changes in MYC target gene expression are not overtly connected to the chromatin remodeling function of rSWI/SNF, revealing multiple mechanisms used by rSWI/SNF to control transcription. This work provides an understanding of how residual SWI/SNF complexes may converge on multiple oncogenic processes when normal SWI/SNF function is impaired.


Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery.
Although previously examined, the potential relationship between preoperative biliary drainage (PBD), intraoperative bile culture (IBC), and postoperative morbidity and mortality rate for pancreatic surgery remains unclear. Two hundred twenty patients underwent operation for either benign pancreatic disease or malignant periampullary and pancreatic neoplasms, consisting of pylorus-preserving proximal pancreatoduodenectomy (n = 180), biliary bypass (n = 31), and total pancreatectomy (n = 9). An intraoperative bile specimen was prospectively collected immediately after division of the bile duct and sent for bacteriologic evaluation for both aerobic and anaerobic microorganisms. Morbidity and mortality rates were evaluated. Of 220 patients evaluated, 113 patients (51.4%) had a positive IBC. Factors associated with a positive IBC were age >70 years (odds ratio [OR], 5.9;95% confidence interval, [CI]: 1.6-22.1; P = .007), history of coronary artery disease (OR, 0.08; 95% CI, 0.01-0.5; P = .007), diagnosis of neoplasia (OR, 0.3; 95% CI, 0.1-0.9; P =. 03), and PBD (OR, 0.1; 95% CI, 0.06-0.2; P = .0001). Infectious complications (OR, 1.8; 95% CI, 1-3; P = .03), and wound infection (OR, 2.8; 95% CI,1.4-5.3; P = .002) were greater in patients with positive IBC. PBD predisposes to a positive IBC. Patients with a positive IBC have a clinically important increased risk of developing both infectious complications and wound infection after pancreatic surgery.


Discovery of tight junction modulators: significance for drug development and delivery.
Tight junction biology has many important applications, from improving knowledge of diseases characterized by the loss of epithelial or endothelial tissue barrier function to providing a mechanistic basis for improving non-invasive drug delivery. A variety of chemical and molecular biological tools have been developed, including high throughput cell-based screening of molecular libraries that facilitate discovery of novel peptides and lipids to modulate tight junction function safely and reversibly. Further development of novel tight junction modulating excipients necessitates consideration of physicochemical, toxicological, pharmaceutical and regulatory issues.


Synthesis of thermal insulator using chicken feather fibre in starch-clay nanocomposites.
Incorporating chicken feather fibre (CFF) into natural based-nanocomposite comprising of glycerine plasticized-cassava starch binder with bentonite (BNT) as nanofiller, a thermal insulator (TIN) was synthesized. Central Composite Design (CCD) Response Surface Methodology was employed to carry out the experimental design using two factors (CFF and BNT) along with one response (thermal conductivity) to produce nine materials as insulators, comprising of 0%, 5%, and 10% BNT based on 8 g initial weight of CFF. A sample without CFF was used as the control. Developed thermal insulators were subjected to thermal conductivity tests using Lee's disc method at a steady state. The best insulator is TIN-4 with the lowest thermal conductivity of 0.0313 W/(mK) and the highest insulation property of 114.63 m2k/W, while TIN-10 with no CFF has the highest thermal conductivity of 0.0549 W/(mk) and lowest insulation property of 48.1603 m2k/W. Proportionate use of chicken feather fibre in starch-clay nanocomposite will help synthesize an effective thermal insulator with minimum cost.


Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: potential for bovine inflammation therapy.
Refractory diseases, including bacterial infections, are causing huge economic losses in dairy farming. Despite efforts to prevent and treat those diseases in cattle, including the use of antimicrobials, it is not well controlled in the field. Several inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), play important roles in disease progression; thus, blocking these cytokines can attenuate the acute and sever inflammation and may be a novel strategy for treatment. However, biological drugs targeting inflammatory cytokines have not been used in cattle. Therefore, in this study, bovine sTNFR1 and sTNFR2 IgG1 Fc-fusion proteins (TNFR1-Ig and TNFR2-Ig) were produced, and their anti-inflammatory functions were analyzed in vitro, to develop decoy receptors for bovine TNF-α. Both TNFR1-Ig and TNFR2-Ig were shown to bind with TNF-α, and TNFR2-Ig showed higher affinity toward TNF-α than TNFR1-Ig. We next stimulated murine fibroblast-derived cells (L929 cells) with TNF-α to induce cell death and analyzed cell viability in the presence of TNFR-Ig proteins. Both TNFR1-Ig and TNFR2-Ig suppressed TNF-α-induced cell death, significantly improving cell viability. In addition, cell death induced by TNF-α was suppressed, even at low TNFR2-Ig concentrations, suggesting TNFR2-Ig has higher activity to suppress TNF-α functions than TNFR1-Ig. Finally, to examine TNFR2-Ig's anti-inflammatory, we cultured peripheral blood mononuclear cells from cattle with TNF-α in the presence of TNFR2-Ig and analyzed the gene expression and protein production of the inflammatory cytokines IL-1β and TNF-α. TNFR2-Ig significantly reduced the gene expression and protein production of these cytokines. Our results suggest that TNFR2-Ig inhibits inflammatory cytokine kinetics by blocking TNF-α to transmembrane TNFR, thereby attenuating excessive inflammation induced by TNF-α. Collectively, the findings of this study demonstrated the potential of TNFR2-Ig as a novel therapeutic for inflammatory diseases, such as bovine clinical mastitis. Further investigation is required for future clinical application.


Aftereffects of frontoparietal theta tACS on verbal working memory: Behavioral and neurophysiological analysis.
Verbal working memory is supported by a left-lateralized frontoparietal theta oscillatory (4-8 Hz) network. We tested whether stimulating the left frontoparietal network at theta frequency during verbal working memory can produce observable after-stimulation effects in behavior and neurophysiology. Weak theta-band alternating electric currents were delivered via two 4 × 1 HD electrode arrays centered at F3 and P3. Three stimulation configurations, including in-phase, anti-phase, or sham, were tested on three different days in a cross-over (within-subject) design. On each test day, the subject underwent three experimental sessions: pre-, during- and post-stimulation sessions. In all sessions, the subject performed a Sternberg verbal working memory task with three levels of memory load (load 2, 4 and 6), imposing three levels of cognitive demand. Analyzing behavioral and EEG data from the post-stimulation session, we report two main observations. First, in-phase stimulation improved task performance in subjects with higher working memory capacity (WMC) under higher memory load (load 6). Second, in-phase stimulation enhanced frontoparietal theta synchrony during working memory retention in subjects with higher WMC under higher memory loads (load 4 and load 6), and the enhanced frontoparietal theta synchronization is mainly driven by enhanced frontal→parietal theta Granger causality. These observations suggest that (1) in-phase theta transcranial alternating current stimulation (tACS) during verbal working memory can result in observable behavioral and neurophysiological consequences post stimulation, (2) the short-term plasticity effects are state- and individual-dependent, and (3) enhanced executive control underlies improved behavioral performance.


Mortality experience of a low-income population with young-onset diabetes.
In young-onset diabetes, insulin therapy status is a rough marker of diabetes type. We describe the mortality experience of a low-income, predominantly minority population with diabetes diagnosed before age 30 years, stratified by insulin therapy. A total of 1,098 adults aged 40-79 years (median 49) diagnosed with diabetes before age 30 years and 49,914 without diabetes were recruited from community health centers. Individuals with diabetes were categorized by insulin therapy at baseline: group A, insulin therapy only; group B, insulin therapy and an oral hypoglycemic agent; and group C, no insulin therapy. Cox models were used to compute hazard ratios (HRs) and 95% CI for cause-specific mortality based on both underlying and contributing causes of death from death certificates. During follow-up (mean 3.9 years), 15.0, 12.5, and 7.3% of groups A, B, and C, respectively, and 4.6% without diabetes died. Compared with individuals without diabetes, HRs (CI) for all-cause mortality were 4.3 (3.4-5.6), 4.2 (2.8-6.3), and 2.0 (1.4-2.8) in groups A, B, and C, respectively. The leading cause of death was renal failure (end-stage renal disease [ESRD]) in group A, ESRD and coronary artery disease (CAD) in group B, and CAD in group C and individuals without diabetes. HRs for these conditions were at least twice as high as the HRs for all-cause mortality, reaching 17.3 (10.2-29.3), 17.9 (8.3-38.7), and 5.1 (2.3-11.7) in groups A, B, and C, respectively, for ESRD. Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality.


Early use of Nasal-BiPAP in two infants with Congenital Central Hypoventilation syndrome.
To reduce the problems caused by prolonged artificial ventilation in babies with Congenital Central Hypoventilation syndrome (CCHS). Two term infants with CCHS, weighing 4030 g and 3100 g, respectively, at the beginning of treatment and aged 53 and 31 d, respectively, were successfully ventilated with a Nasal Bilevel Positive Airway Pressure (N-BiPAP) device. In the first patient the tcPO2 recordings (mean +/- SD) during sleep were 46 +/- 12 mmHg before using N-BiPAP and 58 +/- 13 mmHg after using the device, while those for tcPCO2 were 75 +/- 9 mmHg and 49 +/- 11 mmHg, respectively. In the second patient tcPO2 during sleep was 42 +/- 3 mmHg before, and 55 +/- 5 after N-BiPAP, and for tcPCO2 the recordings were 119 +/- 24 mmHg and 55 +/- 6 mmHg, respectively, showing a significant improvement. One infant had persistent gastro-oesophageal reflux, and frontal skin abrasion caused by the face mask. Nevertheless, these complications did not necessitate the discontinuation of N-BiPAP ventilation, thus precluding prolonged use of intubation and tracheotomy. In infants with CCHS, early use of non-invasive, positive-pressure ventilation with N-BiPAP, in association with careful monitoring, can decrease problems caused by prolonged intubation and tracheotomy.


Rapid glucocorticoid effects on immune cells.
Apart from their classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomically mediated effects. Three different mechanisms are currently under discussion as being responsible for these effects: (1) specific interaction with the cytosolic glucocorticoid receptor (cGCR), (2) nonspecific interactions with cellular membranes and (3) specific interactions with membrane-bound glucocorticoid receptors (mGCR). With regard to the first mechanism, there is evidence that although the binding of glucocorticoids to the cGCR-associated multi-protein complex induces the further processes of the classic path, it also leads to a rapid intracellular signalling through other components of the complex (e.g. Src). For the second mechanism, a nonspecific interactive effect with cellular membranes through the intercalation of glucocorticoid molecules is being discussed, which primarily alters cellular functions by influencing cation transport via the plasma membrane and by increasing the proton leak of the mitochondria. With regard to the third, mGCR-mediated mechanism, the first evidence has now been found to suggest a physiological expression of membrane-bound glucocorticoid receptors on human cells, whereas in humans this had previously only been demonstrated on lymphoma cells. The clinical importance and therapeutic relevance of these rapid glucocorticoid effects remains unclear at present, although effects on intracellular signalling, interferences with bioenergetically relevant cell functions and the induction of apoptosis via the mGCR are being discussed. This article gives a detailed presentation of the data available at present concerning rapid glucocorticoid effects on immune cells.


[Species diversity of the genus Candida in the oral cavity of cancer patients in Barranquilla, Colombia].
Candida spp. was characterized in the oral cavity of cancer patients in a health care center in Barranquilla, Colombia. This is a cross-sectional investigation including 60 oncological patients with oral candidiasis, selected by convenience sampling, from whom samples were subjected to culture in Sabouraud chloramphenicol agar, CHROMagar® Candida and Sabouraud dextrose agar were taken. The antifungal susceptibility profile was then identified and established. Descriptive statistics, Chi square test, and bivariate analysis were conducted using the Statgraphics Centurion XVII software with odds ratio (OR) for the probability of occurrence. A total of 107 Candida strains were identified belonging to 15 species, C. albicans with 23%, C. glabrata with 18%, C. tropicalis 13%, C. krusei 10%, C intermedia, and C. lipolytica with 1.5%. Species other than C. albicans were identified in 77% of the cases. A relationship between reproductive system cancer and C. guilliermondii was identified (p = 0.0001, <0.05) OR: 17.0. Between C. colliculosa and respiratory cancer (p = 0.0003, <0.05) OR 19.5. With regard to antifungal susceptibility, 99% of the identified Candida species were susceptible to the following antifungals: fluconazole, voriconazole, caspofungin, and micafungin. Only one strain of C. krusei was resistant. It is concluded that there was a diversity of Candida species, either single or mixed in cancer patients, which could determine that only one species is not responsible for fungal infection in the oral cavity.


Echocardiographic parameters in patients with pulmonary arterial hypertension: correlations with right ventricular ejection fraction derived from cardiac magnetic resonance and hemodynamics.
Echocardiography is the most convenient method used to evaluate right ventricular function, and several echocardiographic parameters were studied in previous studies. But the value of these parameters to assess the right ventricular function in patients with pulmonary arterial hypertension (PAH) has not been well defined. Patients with PAH were observed prospectively. Right heart catheterization, echocardiography and cardiac magnetic resonance (CMR) were performed within 1 week interval. The correlations between echocardiographic parameters and right ventricular ejection fraction (RVEF) derived from CMR as well as hemodynamics were analyzed. Thirty patients were enrolled including 24 with idiopathic PAH, 5 with PAH associated with connective tissue diseases and 1 with hereditary PAH. All echocardiographic parameters except right ventricular myocardial performance index (RVMPI) correlated significantly with RVEF (tricuspid annual plane systolic excursion [TAPSE], r = 0.440, P = 0.015; tricuspid annular systolic excursion velocity [S'], r = 0.444, P = 0.016; isovolumic acceleration [IVA], r = 0.600, P = 0.001; right ventricular fraction area change [RVFAC], r = 0.416, P = 0.022; ratio of right ventricular transverse diameter to left ventricular transverse diameter [RVETD/LVETD], r = -0.649, P<0.001; RVMPI, r = -0.027, P = 0.888). After adjusted for mean right atrial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance (PVR), only IVA and RVETD/LVETD could independently predict RVEF. Four echocardiographic parameters displayed significant correlations with PVR (TAPSE, r = -0.615, P<0.001; S', r = -0.557, P = 0.002; RVFAC, r = -0.454, P = 0.012; RVETD/LVETD, r = 0.543, P = 0.002). The echocardiographic parameters IVA and RVETD/LVETD can reflect RVEF independently regardless of hemodynamics in patients with PAH. In addition, TAPSE, S', RVFAC and RVETD/LVETD can also reflect PVR in PAH patients.


Heavy ion carcinogenesis and human space exploration.
Before the human exploration of Mars or long-duration missions on the Earth's moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been shown to produce distinct biological damage compared with radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, and obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets.


A retrospective evaluation of Randall's plaque theory of nephrolithiasis with CT attenuation values.
We examined the computed tomography attenuation values (HU) of renal papillae in stone formers (SF) to determine whether nephrolithiasis is associated with radiographic changes in renal papillae to investigate the Randall's plaque theory. Two observers independently and retrospectively recorded the HU of the renal medullae and cortex in 90 patients with a unilateral single calculus within kidney or ureter, and in 104 cases in control group (CG) matched for age and renal functions. The patient ages were similar in the stone former and control groups. However, the male-female ratio was significantly greater in the SF group (68:22) than in the CG (42:62, P<0.0001). Left-right ratio in SF group was 50:40. The inter-rater agreement was kappa=0.53 (95% CI: 0.42, 0.64). Mean HU of all papillae of affected side in stone-formers (ASSF) was significantly greater than that in CG (39.6 versus 29.6, P<0.0001). When comparing affected and non-affected sides within the SF group, there was no significant difference (39.6 versus 38.4, P=0.16). The receiver operating characteristic (ROC) analysis showed area under curve=0.94 with optimal cut-off at 34 HU. At this point the specificity, sensitivity, PPV and NPV were 90%, 90%, 33% and 99%, respectively. HU of the renal papilla is significantly increased in SF in the affected and the non-affected kidneys when compared to the CG. This finding may form one of the risk indicators to determine the future follow up and clinical management for the potential SF.


Cucumber mosaic virus-associated RNA 5. VI. Characterization and denaturation-renaturation behavior of the double-stranded form.
The double-stranded form of cucumber mosaic virus-associated RNA 5 has been purified and further characterized. Its molecular weight determined by sedimentation equilibrium is 2.15 . 10(5). The buoyant density calculated from its symmetrical distribution in Cs2SO4, following isopycnic ultracentrifugation, is 1.615 g/cm3. The sedimentation rate of double-stranded cucumber mosaic virus-associated RNA 5 is slightly greater than that of cucumber mosaic virus-associated RNA 5; its electrophoretic mobility in polyacrylamide gel (2.4%) is less than that of cucumber mosaic virus-associated RNA 5. By the above standards the double-stranded cucumber mosaic virus-associated RNA 5 preparations used were found to be nomogeneous in size as well as density. Thermal denaturation monitored by means of ultraviolet light absorption produced multitransitional denaturation profiles. The average melting temperature (Tm) was 88 degrees C in 0.1 x SSC. Monotransitional denaturation profiles and slightly higher Tm values were obtained when resistance against ribonuclease digestion was measured. These denaturation experiments and other propertied led to the conclusion that double-stranded cucumber mosaic virus-associated RNA 5 and the double-stranded form of peanut stunt virus-associated RNA 5 are small double-stranded nucleic acids with several homostable base-pair regions, characterized by distinct G + C contents and Tm values.


Cytomegalovirus infection in early childhood may be protective against glioblastoma multiforme, while later infection is a risk factor.
Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Recently, evidence for a viral cause has been postulated, possibly cytomegalovirus (CMV). In one report, 80% of patients with newly diagnosed glioblastoma multiforme had detectable cytomegalovirus DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus. However, another study reported that five glioblastoma patients showed no circulating CMV detected either with RT-PCR or blood culture. But CMV could still be a factor in the genesis of glioblastoma multiforme, if age at infection is taken into account, since the incidence of both glioblastoma multiforme and CMV infection are inversely related to socioeconomic status. CMV infection in early childhood, more common in lower socioeconomic groups, may be protective against glioblastoma multiforme, whereas CMV infection in later childhood or adulthood may be a risk factor for glioblastoma. If so, glioblastoma multiforme occurrence would resemble paralytic polio, where low socioeconomic status, poor hygiene and early infection are protective.


Circular RNAs: The star molecules in cancer.
Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs with a closed loop structure. These RNAs are produced by pre-mRNA through variable shear processing and are highly conserved. Such highly conserved molecules play an important role in biology, especially in cancer biology. With the development of experimental techniques such as circRNA microarray screening and high-throughput sequencing technologies, the mystery of circRNAs has gradually been unveiled and the values of function and application have gradually emerged. Among them, cancer-related circRNAs are the most eye-catching. Numerous studies have shown that some circRNAs were involved in the pathogenesis of cancer. This review systematically introduced the cancer-related circRNAs and their origin, formation mechanisms, functions, and applications in the diagnosis and treatment of sixteen kinds of tumors.


The impact of delirium on withdrawal of life-sustaining treatment after intracerebral hemorrhage.
To determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry. We performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score-based models with and without delirium category in predicting WLST. Of 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1-2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0-6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1-37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863-0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909-0.962], p = 0.004). Delirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.


Expression of co-inhibitory molecules B7-H4 and B7-H1 in Epstein-Barr virus positive diffuse large B-cell lymphoma and their roles in tumor invasion.
To investigate the relationship between immunoregulatory molecules B7-H4 and B7-H1 in Epstein-Barr positive diffuse large B-cell lymphoma (EBV+DLBCL). Immunohistochemistry was used to detect the expression of B7-H4 and B7-H1 in tumor tissues of 13 patients with EBV+DLBCL. The expression levels of B7-H4 and B7-H1 in four diffuse large B-cell lymphoma cell lines (SU-DHL-4, SU-DHL-10, SU-DHL-6, Pfeiffer) were analyzed by flow cytometry. Transwell invasion assays were conducted to observe the invasive ability of cell lines. B7-H4 and B7-H1 were expressed in 84.62% and 100% tumor specimens of EBV+DLBCL. The overexpression of B7-H4 and B7-H1 was found in 46.15% and 23.08% tumor samples of EBV+DLBCL. There was a medium negative correlation between the expression levels of B7-H4 and B7-H1 (r = -0.667, P = 0.013, spearman rank correlation). The expression levels of B7-H1 in four diffuse large B-cell lymphoma cell lines were positively correlated with their invasive ability, whereas the expression levels of B7-H4 were not. Here, we provide evidence for the negative relationship between B7-H4 and B7-H1 in EBV+DLBCL. The expression of B7-H1 in EBV+DLBCL appears to be the dominant factor which affects tumor aggressiveness. When B7-H1 expression weakens, the molecule B7-H4 may become the dominant factor of prognosis in patients with EBV+DLBCL.


Use of 123I-IMP brain SPET to predict outcome following STA-MCA bypass surgery: cerebral blood flow but not vasoreactivity is a predictive parameter.
Superficial temporal artery - middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine (123I-IMP) brain single-photon emission tomography (SPET). 123I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide c hallenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide - rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5 +/- 19.3 years) into group I, who h a change in their resting CBF from before to after surgery of >10%, and 16 patients (54.0 +/- 18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ¿leq10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P<0.05). Resting CBF improved by 20.4% +/- 7.5% in group I and by 0.9% +/- 6.9% in group II patients after surgery (P<0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6% +/- 17.7%) and group II patients (24.6% +/- 15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59 +/- 0.09 before surgery to 0.46 +/- 0.06 after surgery (P<0.05), while patients in the group II PET subset showed no statistical difference in OEF before surgery (0.58 +/- 0.14) and after surgery (0.54 +/- 0.05). We conclude that the outcome of STA-MCA bypass surgery can be predicted by the improvement in resting CBF but not by the improvement in vasoreactivity.


Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.
Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay. The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes. Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.


Explainable hybrid word representations for sentiment analysis of financial news.
Due to the increasing interest of people in the stock and financial market, the sentiment analysis of news and texts related to the sector is of utmost importance. This helps the potential investors in deciding what company to invest in and what are their long-term benefits. However, it is challenging to analyze the sentiments of texts related to the financial domain, given the enormous amount of information available. The existing approaches are unable to capture complex attributes of language such as word usage, including semantics and syntax throughout the context, and polysemy in the context. Further, these approaches failed to interpret the models' predictability, which is obscure to humans. Models' interpretability to justify the predictions has remained largely unexplored and has become important to engender users' trust in the predictions by providing insight into the model prediction. Accordingly, in this paper, we present an explainable hybrid word representation that first augments the data to address the class imbalance issue and then integrates three embeddings to involve polysemy in context, semantics, and syntax in a context. We then fed our proposed word representation to a convolutional neural network (CNN) with attention to capture the sentiment. The experimental results show that our model outperforms several baselines of both classic classifiers and combinations of various word embedding models in the sentiment analysis of financial news. The experimental results also show that the proposed model outperforms several baselines of word embeddings and contextual embeddings when they are separately fed to a neural network model. Further, we show the explainability of the proposed method by presenting the visualization results to explain the reason for a prediction in the sentiment analysis of financial news.


Investigating Ethnic Disparity in Living-Donor Kidney Transplantation in the UK: Patient-Identified Reasons for Non-Donation among Family Members.
There is ethnic inequity in access to living-donor kidney transplants in the UK. This study asked kidney patients from Black, Asian and minority ethnic groups why members of their family were not able to be living kidney donors. Responses were compared with responses from White individuals. This questionnaire-based mixed-methods study included adults transplanted between 1/4/13-31/3/17 at 14 UK hospitals. Participants were asked to indicate why relatives could not donate, selecting all options applicable from: Age; Health; Weight; Location; Financial/Cost; Job; Blood group; No-one to care for them after donation. A box entitled 'Other-please give details' was provided for free-text entries. Multivariable logistic regression was used to analyse the association between the likelihood of selecting each reason for non-donation and the participant's self-reported ethnicity. Qualitative responses were analysed using inductive thematic analysis. In total, 1240 questionnaires were returned (40% response). There was strong evidence that Black, Asian and minority ethnic group individuals were more likely than White people to indicate that family members lived too far away to donate (adjusted odds ratio (aOR) = 3.25, 95% Confidence Interval (CI) 2.30-4.58), were prevented from donating by financial concerns (aOR = 2.95, 95% CI 2.02-4.29), were unable to take time off work (aOR = 1.88, 95% CI 1.18-3.02), were "not the right blood group" (aOR = 1.65, 95% CI 1.35-2.01), or had no-one to care for them post-donation (aOR = 3.73, 95% CI 2.60-5.35). Four qualitative themes were identified from responses from Black, Asian and minority ethnic group participants: 'Burden of disease within the family'; 'Differing religious interpretations'; 'Geographical concerns'; and 'A culture of silence'. Patients perceive barriers to living kidney donation in the UK Black, Asian and minority ethnic population. If confirmed, these could be targeted by interventions to redress the observed ethnic inequity.


Healthcare professionals' sources of knowledge of complementary medicine in an academic center.
Complementary medicine (CM) is utilized in a growing number of academic centers despite the debate concerning its value, risks and benefits. Healthcare professionals often feel uncomfortable discussing CM with patients, and little is known about their sources of knowledge in the field of CM. To assess healthcare professionals' sources of knowledge and attitude toward CM in an academic hospital. The cross-sectional web-based survey took place from October to December 2013. A total of 4,925 healthcare professionals working at Lausanne University Hospital, Switzerland, were invited to answer the questionnaire. Factors influencing healthcare professionals' opinion toward CM, knowledge and communication about CM. The questionnaire was answered by 1,247 healthcare professionals. The three key factors influencing professionals' opinion toward CM were personal experience, clinical experience and evidence demonstrating the physiological mechanism of CM. Personal experience was more associated with nurses' and midwives' opinion compared to physicians' (80.8% vs 57.1%, OR = 3.08, [95% CI: 2.35-4.05], P<0.001 and 85.3% vs 57.1%, OR = 3.83, [95% CI: 1.95-7.53], P<0.001, respectively) as well as with professionals trained in CM compared to non-trained professionals (86.0% vs 73.2%, OR = 2.60, [95% CI: 1.92-3.53], P<0.001). Physicians relied more on randomized controlled clinical trials compared to nurses (81.3% vs 62.9%, OR = 0.43, [95% CI: 0.33-0.57], P<0.001). A majority of the respondents (82.5%) agreed that they lacked knowledge about CM and 65.0% noted that it was the patient who initially started the discussion about CM. Different professionals used different strategies to forge opinions regarding CM: physicians relied more on scientific evidence, while nurses and midwives were more influenced by personal experience. Regardless of preferred information source, most respondents did not feel prepared to address patient questions regarding CM. Enhancing interprofessional education opportunities is an important strategy to help providers become empowered to discuss CM with patients. This in turn will help patients making informed decisions in their healthcare.


Multisensory Testing Framework for Advanced Driver Assistant Systems Supported by High-Quality 3D Simulation.
ADAS and autonomous technologies in vehicles become more and more complex, which increases development time and expenses. This paper presents a new real-time ADAS multisensory validation system, which can speed up the development and implementation processes while lowering its cost. The proposed test system integrates a high-quality 3D CARLA simulator with a real-time-based automation platform. We present system experimental verifications on several types of sensors and testing system architectures. The first, open-loop experiment explains the real-time capabilities of the system based on the Mobileye 6 camera sensor detections. The second experiment runs a real-time closed-loop test of a lane-keeping algorithm (LKA) based on the Mobileye 6 line detection. The last experiment presents a simulation of Velodyne VLP-16 lidar, which runs a free space detection algorithm. Simulated lidar output is compared with the real lidar performance. We show that the platform generates reproducible results and allows closed-loop operation which, combined with a real-time collection of event information, promises good scalability toward complex ADAS or autonomous functionalities testing.


Associations of socioeconomic status and lifestyle factors with dental neglect of elementary school children: the MEXT Super Shokuiku School Project.
Despite the fact that there are parents who do not take children with untreated dental caries to a dental clinic, few studies have been conducted to identify the responsible underlying social and family factors. The aim of this study was to investigate whether socioeconomic status and lifestyle factors are associated with dental neglect in elementary school children. This study was conducted in 2016 with 1655 children from the Super Shokuiku School Project in Toyama. Using Breslow's seven health behaviors, the survey assessed: the grade, sex, and lifestyle of the children; parental internet and game use and lifestyle; socioeconomic status. The odds ratios (OR) and 95% confidence intervals (CIs) for having untreated dental caries were calculated using logistic regression analysis. Among the children participating, 152 (3.2%) had untreated dental caries. Among them, 53 (34.9%) had not been taken to a dental clinic despite the school dentist's advice. Dental neglect was significantly associated with children in higher grades (OR, 2.08; 95% CI, 1.14-3.78), father's Internet and game use ≥ 2 h/day (OR, 1.99; 95% CI, 1.02-3.88), not being affluent (OR, 2.78; 95% CI, 1.14-6.81), and non-engagement in afterschool activities (OR, 1.99; 95% CI, 1.10-3.62). Socioeconomic status was the strongest factor associated with dental neglect despite the fact that the children's medical expenses are paid in full by the National Health Insurance in Toyama, Japan. Future studies should investigate what factors prevent parents of non-affluent families from taking their children to dental clinics and how they can be socially supported to access adequate medical care.


The recolonization potential of Metridium senile in an area previously depopulated by oxygen deficiency.
Every summer the deepest parts of the inner Flensburg fjord are subject to O2-deficiency lasting from a few weeks to several months. In spring, however, populations of Metridium senile can be found in these areas, in spite of the fact that frequently the local anoxic period of the previous summer has been 2-3 times longer than their anoxia LD50-value (3 wks).Responsible for this phenomenon is an intensive recolonization by adult Metridium during autumn and winter. This process has been investigated in an 8 months monitoring from May to December 1981. Results on the recolonization mechanism, the population structure of immigrating anemones and recolonization rate as a function of available hard substratum are presented.


Lipid saturation and head group composition have a pronounced influence on the membrane insertion equilibrium of amphipathic helical polypeptides.
The histidine-rich peptides of the LAH4 family were designed using cationic antimicrobial peptides such as magainin and PGLa as templates. The LAH4 amphipathic helical sequences exhibit a multitude of interesting biological properties such as antimicrobial activity, cell penetration of a large variety of cargo and lentiviral transduction enhancement. The parent peptide associates with lipid bilayers where it changes from an orientation along the membrane interface into a transmembrane configuration in a pH-dependent manner. Here we show that LAH4 adopts a transmembrane configuration in fully saturated DMPC membranes already at pH 3.5, i.e. much below the pKa of the histidines whereas the transition pH in POPC correlates closely with histidine neutralization. In contrast in POPG membranes the in-planar configuration is stabilized by about one pH unit. The differences in pH can be converted into energetic contributions for the in-plane to transmembrane transition equilibrium, where the shift in the transition pH due to lipid saturation corresponds to energies which are otherwise obtained by the exchange of several cationic with hydrophobic residues. A similar dependence on lipid saturation has also been observed when the PGLa and magainin antimicrobial peptides interact within lipid bilayers suggesting that the quantitative evaluation presented in this paper also applies to other membrane polypeptides.


Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder.
To evaluate the single- and multiple-dose pharmacokinetics of an oral extended-release formulation of guanfacine in children and adolescents with a diagnosis of attention-deficit-hyperactivity disorder (ADHD). Phase I-II, open-label, dose-escalation study. Clinical study center. Fourteen children (aged 6-12 yrs) and 14 adolescents (aged 13-17 yrs) with ADHD. All patients received guanfacine as a single 2-mg dose on day 1. They received a daily dose of 2 mg on days 9-15, 3 mg on days 16-22, and 4 mg on days 23-29. Blood samples, vital signs, and electrocardiograms (ECGs) were obtained before dosing on day 1 and at intervals over 24 hours, with repeat measurements on days 14 and 28. Guanfacine demonstrated linear pharmacokinetics. Mean plasma concentrations, peak exposure (C(max)), and total or 24-hour exposure (area under the concentration-time curve [AUC](0-infinity) or AUC(0-24), respectively) were as follows in children and adolescents, respectively: after a single 2-mg dose, AUC(0-infinity) was 65.2 +/- 23.9 ng x hour/ml and 47.3 +/- 13.7 ng x hour/ml and C(max) was 2.55 +/- 1.03 ng x ml and 1.69 +/- 0.43 ng/ml after multiple 2-mg doses, AUC(0-24) was 70.0 +/- 28.3 ng x hour/ml and 48.2 +/- 16.1 ng x hour/ml and C(max) was 4.39 +/- 1.66 ng/ml and 2.86 +/- 0.77 ng/ml; and after multiple 4-mg doses, AUC(0-24) was 162 +/- 116 ng x hour/ml and 117 +/- 28.4 ng x hour/ml and C(max) was 10.1 +/- 7.09 ng/ml and 7.01 +/- 1.53 ng/ml. After a single 2-mg dose, half-life was 14.4 +/- 2.39 hours in children and 17.9 +/- 5.77 hours in adolescents. The most frequent treatment-emergent adverse events were somnolence, insomnia, headache, blurred vision, and altered mood. Most were mild to moderate in severity, with the highest frequency associated with the 4-mg doses. Blood pressure, pulse, and ECG reading.hour/ml s were all within normal limits. Guanfacine extended-release formulation demonstrated linear pharmacokinetics. Plasma concentrations and concentration-related pharmacokinetic parameters were higher in children than in adolescents. These differences are likely due to heavier body weights in adolescents and young male subjects. No serious adverse events were reported.


Transcatheter treatment of muscular ventricular septal defect and pulmonary valvar stenosis in an infant.
An 11-month-old, 8 kg girl with muscular ventricular septal defect and pulmonary valvar stenosis had successful transcatheter treatment of both anomalies. The stenotic pulmonary valve was dilated first by balloon catheter, then the VSD was approached and closed using a 6 mm Amplatzer VSD occluder device. Due to technological improvements, transcatheter techniques are more and more the procedure of choice in a larger number of congenital heart diseases in younger and younger patients.


Bioinformatic investigation for candidate genes and molecular mechanism in the pathogenesis of membranous nephropathy.
We aimed to explore the detailed molecular mechanism of immune-associated genes in membranous nephropathy (MN). A microarray data set (GSE133288) was retrieved from the Gene Expression Omnibus database. Differentially expressed mRNAs (DEMs) in MN vs control groups were identified, and MN-related DEMs (MN-DEMs) were further verified and screened using the comparative toxicogenomics database (CTD) database. The publicly available database, InnateDB was used to investigate immune genes, and the overlapped genes between MN-DEMs and the immune genes were considered as MN-related immune genes (iDEMs). A protein-protein interaction network (PPI) was constructed based on these iDEMs, followed by function and pathway enrichment analysis. Finally, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) associated with iDEMs were predicted, followed by a lncRNA-miRNA-mRNA (competing endogenous RNAs, ceRNA) network construction. A total of 327 DEMs and 48 iDEMs were revealed; a PPI network was constructed with 100 PPI pairs and 37 iDEMs. iDEMs including JUN and FOS were mainly enriched in pathways such as osteoclast differentiation and function including response to immobilization stress, respectively. Based on mRNA-associated miRNA and lncRNA prediction, 30 ceRNA interactions including KCNQ1OT1-miR-204-5p-SRY-Box Transcription Factor 4 (SOX4) were explored. mRNAs including FOS and JUN might participate in MN development via response to immobilization stress function and the osteoclast differentiation pathway. The mRNA SOX4 might contribute to MN progression via sponging KCNQ1OT1-miR-204-5p interaction.


Efficacy of chest X-rays after drain removal in adult and pediatric patients undergoing cardiac and thoracic surgery: A systematic review.
Chest X-rays are routinely obtained after the removal of chest drains in patients undergoing cardiac and thoracic surgical procedures. However, a lack of guidelines and evidence could question the practice. Routine chest X-rays increase exposure to ionizing radiation, increase health-care costs, and lead to overutilisation of available resources. This review aims to explore the evidence in the literature regarding the routine use of chest X-rays following the removal of chest drains. A systematic literature search was conducted in PubMed, Medline via Ovid, Cochrane central register of control trials (CENTRAL), and ClinicalTrials. gov without any limit on the publication year. The references of the included studies are manually screened to identify potentially eligible studies. A total of 375 studies were retrieved through the search and 18 studies were included in the review. Incidence of pneumothorax remains less than 10% across adult cardiac, and pediatric cardiac and thoracic surgical populations. The incidence may be as high as 50% in adult thoracic surgical patients. However, the reintervention rate remains less than 2% across the populations. Development of respiratory and cardiovascular symptoms can adequately guide for a chest X-ray following the drain removal. As an alternative, bedside ultrasound can be used to detect pneumothorax in the thorax after the removal of a chest drain without the need for ionizing radiation. A routine chest X-ray following chest drain removal in adult and pediatric patients undergoing cardiac and thoracic surgery is not necessary. It can be omitted without compromising patient safety. Obtaining a chest X-ray should be clinically guided. Alternatively, bedside ultrasound can be used for the same purpose without the need for radiation exposure.


Spatial heterogeneity of the associations of economic and health care factors with infant mortality in China using geographically weighted regression and spatial clustering.
Economic factors and health care resources are important influential factors of infant mortality. We aimed to examine prefecture-level spatial heterogeneity and clustering of the associations of economic and health care factors with infant mortality rates (IMR) in China. IMR data in 348 prefectures were calculated and adjusted, and economic and health care data were collected in each prefecture in China, 2010. Stepwise regression was used to select important variables, and geographically weighted regression (GWR) was applied to examine the spatial variations of the relationships between economic and health care factors and IMR. The k-means clustering was developed to elucidate the spatial clustering patterns of the GWR coefficients. The results showed that three important variables were selected in the multivariable regression model, including per capita income of rural residents, Engel's coefficient of rural residents, and proportion of government health expenditure. The GWR with these three variables revealed spatial heterogeneity of the associations between IMR and economic and health care factors; western China generally had higher GWR R-squares and stronger associations between IMR and all the three variables than the middle-eastern part of China. Based on the GWR coefficients, three distinct spatial clusters were identified. This study contributes new findings on the spatial heterogeneity of the associations between economic and health care factors and infant mortality rate in China, which calls for region-specific policies to reduce infant mortality in China.


Comparison of the labeling efficiency of BrdU, DiI and FISH labeling techniques in bone marrow stromal cells.
Cells are generally labeled during in vivo implantation studies enabling the cells to be traced. The relationship between the labeling efficiency and cellular proliferation after transplantation is critical for the interpretation of data obtained by detection of the signals on tissue sections. Here, we compare cellular labeling methods of rat marrow stromal cells that were labeled with 5-bromo-2-deoxyuridine (BrdU), 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and fluorescence in situ hybridization (FISH). Our data show that (i) BrdU uniformly labeled the nuclei, (ii) DiI-labeled cells had many dots or stained clear and uniform when a longer exposure time was used during detection and (iii) FISH labeled the cells with dots along the edges of the nuclei. The labeling efficiency was 94.1+/-8.6%, 97.6+/-3.4% and 90.5+/-3.0%, in BrdU, DiI- and FISH-labeled cells, respectively. After sub-culturing of labeled cells, the percentage of BrdU-positive cells was found to be 71.9+/-18.0% and 18.4+/-6.9%, after the first and second passages, respectively. The percentage of DiI-labeled cells detected depended on the exposure time: a long exposure time (>10 s) resulted in identification of 95.1+/-4.0% and 94.5+/-3.9% DiI-positive cells after the first and second sub-cultures, respectively. The percentage of FISH-positive cells was found to be 87.0+/-3.0% and 89.1+/-9.7%. The BrdU labeling signal quickly decreased over time. Thus, BrdU should only be used to temporarily label dividing cells. In contrast, our data indicate that DiI and FISH labeling may be used to steadily trace cells during in vivo experiments. To our knowledge, this is the first time that the effects of different labeling methods over time have been examined during a cell transplantation study.


[Quality of life of patients with nonfunctioning pituitary adenoma: a meta-analysis].
To evaluate the quality of life (QoL) of patients with nonfunctioning pituitary adenoma (NFPA) after systematic treatment. We searched all published articles involving in the QoL of patients with NFPA on line, and analyzed the results by the Revman5.3 software. Five studies met the criteria of meta-analysis.The results of meta-analysis wereas follows: Physical function MD=0.76, 95%CI (-4.13, 5.64 ), P=0.76; Physical prole MD=-2.05, 95%CI (-7.41, 3.31), P=0.45; Body pain MD=3.50, 95%CI (1.11, 5.90), P=0.004; General health MD=-7.19, 95%CI (-12.77, -1.61), P=0.01; Vatility MD=-3.48, 95%CI (-7.39, 0.43), P=0.08; Social function MD=-4.64, 95%CI (-6.99, -2.38), P<0.000 1; Mental health MD=-0.05, 95%CI (-2.30, 2.20), P=0.96; Role emotion MD=-5.08, 95%CI (-8.20, -1.91), P=0.002. This meta-analysisindicated thatthe QoL of patients with NFPA was damaged on the dimensions of general health, social function and role emotion.The dimension of physical painin patients with NFPA was better than that in general population, and there was no difference between other health dimensions.


Phosphosugars are potent inhibitors of central nervous system inflammation.
Adoptively transferred allergic encephalomyelitis can be inhibited by various phosphosugars, particularly mannose-6-phosphate. The sugar specificity suggests that inhibition may be due to depletion of lymphocyte cell-surface lysosomal enzymes, which are essential for the passage of lymphocytes across the vascular endothelium and the entry of lymphocytes into the central nervous system parenchyma.


Experimental dataset investigating the effect of temperature in the presence or absence of catalysts on the pyrolysis of plantain and yam peels for bio-oil production.
More than 1.3 billion tons, a third of the total food produced, is wasted annually, and it has been predicted to increase in the coming years. Food waste significantly contributes to greenhouse gas (GHG) emissions resulting in the release of about 3.3 billion tonnes of CO2 into the environment yearly. Hence this large amount of wastes, with adverse environmental effects, needs to be appropriately managed. New technologies such as Anaerobic digestion, fermentation, and gasification are being used to produce renewable energy, which in turn reduces the increasing level of food wastes in the environment. Pyrolysis of biomass materials or food wastes produces high-value energy products or bio-oil that can possibly replace non-renewable fossil fuels when it is upgraded. In this study, pyrolysis (thermal treatment in the absence of oxygen) of plantain and yam peels to produce bio-oil, was investigated. The pyrolysis conditions, wide temperature ranges at an interval of 100 °C (200-700 °C), absence of a catalyst (AOC), the use of zeolite -Y catalyst using two separate heterogeneous catalysis procedures were imposed and used to produced bio-oil. In the first procedure, the pyrolysis gases were allowed to rise through a zeolite-Y catalyst bed (HTC). And in the second procedure, the plantain or yam peel feedstock was first mixed uniformly with the zeolite-Y catalyst before pyrolysis (HMC). The GC-MS machine was used to analyze or characterize the obtained bio-oil while proximate analysis and XRF machine were used to characterize the plantain and yam peels feed. The residue, biochar, from the pyrolysis process, was also characterized using the XRF machine.


Prenatal diagnosis of propionic acidemia by measuring methylcitric acid in dried amniotic fluid on filter paper using GC/MS.
Propionic acidemia is a frequent inborn error of metabolism. Methylcitric acid, a key indicator of propionic acidemia, increases in the amniotic fluid of affected fetuses. For prenatal diagnosis, the methylcitric acid in amniotic fluid can be measured by stable-isotope dilution GC/MS. Here, we quantified this indicator in samples of amniotic fluid that had been dried on filter paper and transported at ambient temperatures, and compared the results with data obtained from the original amniotic fluid. We then used the filter-paper method to screen at-risk fetuses and obtained a clear-cut diagnosis in each case.


Pineal N-acetyltransferase and hydroxyindole-O-methyltransferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus.
The visual pathway and central neural structures involved in the photic and endogenous regulation of the activity of pineal N-acetyltransferase and hydroxyindole-O-methyltransferase were investigated. The results indicate that the visual pathway regulating both enzymes is the retinohypothalamic tract, and that the inferior accessory optic tract is clearly not involved in the regulation of hydroxyindole-O-methyltransferase activity, as has been previously thought. In addition, the suprachiasmatic nucleus was found to be necessary for the generation of a rhythm in N-acetyltransferase activity in blinded animals, and to be responsible for the tonic elevation of hydroxyindole-O-methyltransferase activity in blinded animals. Finally, it was concluded that the rapid and large daily changes in N-acetyltransferase activity seen in a normal lighting cycle and the much slower and smaller changes in hydroxyindole-O-methyltransferase activity seen only after weeks in constant lighting conditions are mediated by the same neural tract; the different time courses of the effects of environmental lighting may be explained on the basis of different intracellular regulatory mechanisms.


Safety and efficacy of intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer in patients with prosthetic devices.
Patients with bladder cancer who have prosthetic devices, such as a cardiac pacemaker, artificial heart valve or orthopedic hardware, and who undergo intravesical bacillus Calmette-Guérin therapy are theoretically at higher risk for complications, including bacterial seeding of pacemaker wires or orthopedic hardware, and at further risk for infective endocarditis. We assessed the safety and efficacy of bacillus Calmette-Guérin plus interferon α-2b therapy in patients with nonmuscle invasive bladder cancer and a pacemaker, artificial heart valve or orthopedic hardware. We evaluated 1,045 patients with nonmuscle invasive bladder cancer enrolled in a multicenter American phase II trial of bacillus Calmette-Guérin plus interferon α-2b therapy, including 143 with a prosthetic device (pacemaker in 87, artificial heart valve in 13 and orthopedic hardware in 43). Weekly physician toxicity assessments and standard adverse effect reporting were done. No patient had infective endocarditis or hardware infection. One patient with a pacemaker, 2 with orthopedic hardware and none with an artificial heart valve required treatment cessation for fever greater than 102.5F. All defervesced within 24 hours and had no long-term sequelae. Due to intolerable, nonlife threatening side effects 12 patients with a pacemaker, 2 with orthopedic hardware and 1 with an artificial heart valve stopped treatment. Of the remaining patients with a prosthesis 99 and 24 stopped treatment due to intolerable, nonlife threatening and serious side effects, respectively. Patients with a pacemaker, artificial heart valve or orthopedic hardware were no more likely than the general population to have infection or fever, or discontinue treatment due to side effects. These patients should not be excluded from intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer.


Left and right atrial speckle tracking: Comparison of three methods of time reference gating.
Atrial function has a close interdependence with ventricular function and plays a central role in maintaining optimal cardiac function. There are two well-defined timing methods used to determine the start point. The aim of this prospective study was to objectively assess the influence of gating method selection on reported left and right strain values within the same group of healthy subjects. 101 volunteers (44 male, 57 female) had adequate tracking for analysis on TomTec Imaging Systems (Unterschleissheim, Germany). The median age was 41 years (range 19-79 years, interquartile range 30-52 years). Atrial strain by 2D-speckle tracking echocardiography was evaluated using two commonly applied zero baseline time reference methods: R-R gating and P-P gating, in addition to volume gating (defining end-systole at the atrial maximum and end-diastole at the atrial minimum). True atrial minimum occurred prior to the onset of the QRS in most healthy volunteers. There was a significant difference for LA and RA reservoir strain between volume gating and R-R gating (mean difference, 4.63%; P < .001 for LA; mean difference, 4.23%; P < .001 for RA), as well as volume gating and P-P gating (mean difference, 5.26%; P < .001 for LA; mean difference, 6.24%; P < .001 for RA). Noticeably, reservoir strain was comparable between R-R gating and P-P gating (mean difference, 0.58%, P = .06) in LA, but not on RA (mean difference, 2.02%, P < .001). There was variability in atrial strain values depending on the zero baseline time reference method used.


Lung function in children following repair of tracheoesophageal fistula.
Lung function and bronchial reactivity by methacholine challenge were studied in 24 patients seven to 18 years after repair of type I tracheoesophageal fistula. Only one patient had no abnormalities of the variables tested. Thirteen patients had obstructive airways disease, five had a restrictive defect, and 15 had a positive methacholine challenge. It is postulated that continuing subclinical aspiration of esophageal contents causes lung damage and renders the airways hyperreactive.


Dermatoscopy of Vascular Lesions.
Cutaneous vascular lesions (VLs) represent a very common reason for dermatologic consultation for patients. In most cases, VLs are benign and self-limiting. However, because they often mimic malignant skin tumors, their correct and prompt identification is very important in daily practice. Dermoscopy may play a key role in achieving that purpose. This article reviews current knowledge of dermoscopic features of the most frequent VLs.


Two centuries of limited variability in subtropical North Atlantic thermocline ventilation.
Ventilation and mixing of oceanic gyres is important to ocean-atmosphere heat and gas transfer, and to mid-latitude nutrient supply. The rates of mode water formation are believed to impact climate and carbon exchange between the surface and mid-depth water over decadal periods. Here, a record of (14)C/(12)C (1780-1940), which is a proxy for vertical ocean mixing, from an annually banded coral from Bermuda, shows limited inter-annual variability and a substantial Suess Effect (the decrease in (14)C/(12)C since 1900). The Sargasso Sea mixing rates between the surface and thermocline varied minimally over the past two centuries, despite changes to mean-hemispheric climate, including the Little Ice Age and variability in the North Atlantic Oscillation. This result indicates that regional formation rates of sub-tropical mode water are stable over decades, and that anthropogenic carbon absorbed by the ocean does not return to the surface at a variable rate.