GPU accelerated generation of digitally reconstructed radiographs for 2-D/3-D image registration.
Recent advances in programming languages for graphics processing units (GPUs) provide developers with a convenient way of implementing applications which can be executed on the CPU and GPU interchangeably. GPUs are becoming relatively cheap, powerful, and widely available hardware components, which can be used to perform intensive calculations. The last decade of hardware performance developments shows that GPU-based computation is progressing significantly faster than CPU-based computation, particularly if one considers the execution of highly parallelisable algorithms. Future predictions illustrate that this trend is likely to continue. In this paper, we introduce a way of accelerating 2-D/3-D image registration by developing a hybrid system which executes on the CPU and utilizes the GPU for parallelizing the generation of digitally reconstructed radiographs (DRRs). Based on the advancements of the GPU over the CPU, it is timely to exploit the benefits of many-core GPU technology by developing algorithms for DRR generation. Although some previous work has investigated the rendering of DRRs using the GPU, this paper investigates approximations which reduce the computational overhead while still maintaining a quality consistent with that needed for 2-D/3-D registration with sufficient accuracy to be clinically acceptable in certain applications of radiation oncology. Furthermore, by comparing implementations of 2-D/3-D registration on the CPU and GPU, we investigate current performance and propose an optimal framework for PC implementations addressing the rigid registration problem. Using this framework, we are able to render DRR images from a 256×256×133 CT volume in ~24 ms using an NVidia GeForce 8800 GTX and in ~2 ms using NVidia GeForce GTX 580. In addition to applications requiring fast automatic patient setup, these levels of performance suggest image-guided radiation therapy at video frame rates is technically feasible using relatively low cost PC architecture.


Evaluation of stationary colposcope and the Gynocular, by the Swede score systematic colposcopic system in VIA positive women: a crossover randomized trial.
This study aimed to evaluate cervical lesions by the Swede coloscopy system, histologic finding, liquid-based cytology, and human papillomavirus (HPV) in women who resulted positive for visual inspection of the cervix with acetic acid (VIA) by using a pocket-sized battery-driven colposcope, the Gynocular (Gynius AB, Sweden). This study was a crossover, randomized clinical trial at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, with 540 VIA-positive women. Swede scores were obtained by the Gynocular and stationary colposcope, as well as samples for liquid-based cytology, HPV, and cervical biopsies. The Swede scores were compared against the histologic diagnosis and used as criterion standard. The percentage agreement and the κ statistic for the Gynocular and standard colposcope were also calculated. The Gynocular and stationary colposcope showed high agreement in Swede scores with a κ statistic of 0.998, P value of less than 0.0001, and no difference in detecting cervical lesions in biopsy. Biopsy detected cervical intraepithelial neoplasia (CIN) 2+ (CIN2, CIN3, and invasive cancer) in 38 (7%) of the women, whereas liquid-based cytology detected CIN2+ in 13 (2.5%) of the women. Forty-four (8.6%) women who were tested resulted positive for HPV; 20 (3.9%) women had HPV-16, 2 (0.4%) had HPV-18, and 22 (4.3%) had other high-risk HPV. Our study showed that few VIA-positive women had CIN2+ lesions or HPV infection. Colposcopy by Swede score identified significantly more CIN2+ lesions than liquid-based cytology and could offer a more accurate screening and selection for immediate treatment of cervical lesions in low-resource settings.


How do the sexual behaviors of foreign-born Hispanic men who have sex with men differ by relationship status?
High-risk sexual behaviors may result in acquisition of sexually transmitted infections including HIV. Hispanic men who have sex with men (MSM) experience a disproportionate incidence of these infections. Various risk factors, cultural aspects, and relationship factors may influence the sexual behaviors of this subgroup of MSM. The purpose of this study was to describe the sexual behaviors of a sample of foreign-born Hispanic MSM and to compare these sexual behaviors in terms of condom usage, risky sexual behaviors, avoidance of body fluids, and sexual negotiation when stratified by relationship status. Using a cross-sectional, descriptive research design, a convenience sample of 135 foreign-born Hispanic MSM, the majority of whom were Cubans, was recruited and surveyed from the South Florida area. The majority of participants reported engaging in the high-risk sexual behaviors of sex without condoms, substance abuse before or during sex, anal sex, contact with body fluids, and did not negotiate safer sex behaviors. Differences in sexual behaviors when compared by relationship status were found only in terms of certain risky sexual behaviors but not in terms of condom usage, contact with body fluids, or sexual negotiation. Despite participation in a number of high-risk activities and finding few differences among those men in relationships and those not in primary relationships, factors that promote or inhibit participation in high-risk sexual behaviors among Hispanic MSM in various types of relationships need further exploration.


Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study.
To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long-term outcome of etanercept treatment. Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute-phase reactants, particularly during asymptomatic periods. During a 10-year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti-interleukin-1β receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup. Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose-dependent manner, but does not completely normalize symptoms or acute-phase reactant levels. Although long-term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit.


[Cloning and expression of cDNA for tobacco rab1, and structural-functional analysis of the protein].
rab1 cDNA coding for a small GTP binding protein Rab1 was isolated from cDNA library of tobacco (Nicotiana tabacum) leaves. The primary structure of this protein was deduced from the rab1 structure. Tobacco rab1 cDNA was expressed in Escherichia coli, and the product was purified and shown to exhibit GTPase activity. A set of Rab1 mutants with altered GTP binding and/or GTPase activities was obtained. Polyclonal antipeptide antibodies were raised against a sequence in the C-terminal region of the tobacco Rab1 capable of recognizing this protein.


Association of COVID-19 with Risk and Progression of Alzheimer's Disease: Non-Overlapping Two-Sample Mendelian Randomization Analysis of 2.6 Million Subjects.
Epidemiological studies showed that COVID-19 increases risk of Alzheimer's disease (AD). However, it remains unknown if there is a potential genetic predispositional effect. To examine potential effects of genetic susceptibility of COVID-19 on the risk and progression of AD, we performed a non-overlapping 2-sample Mendelian randomization (MR) study using summary statistics from genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis of over 2.6 million subjects was used to examine whether genetic susceptibility of COVID-19 is not associated with the risk of AD, cortical amyloid burden, hippocampal volume, or AD progression score. Additionally, a validation analysis was performed on a combined sample size of 536,190 participants. We show that the AD risk was not associated with genetic susceptibility of COVID-19 risk (OR = 0.98, 95% CI 0.81-1.19) and COVID-19 severity (COVID-19 hospitalization: OR = 0.98, 95% CI 0.9-1.07, and critical COVID-19: OR = 0.98, 95% CI 0.92-1.03). Genetic predisposition to COVID-19 is not associated with AD progression as measured by hippocampal volume, cortical amyloid beta load, and AD progression score. These findings were replicated in a set of 536,190 participants. Consistent results were obtained across models based on different GWAS summary statistics, MR estimators and COVID-19 definitions. Our findings indicated that the genetic susceptibility of COVID-19 is not associated with the risk and progression of AD.


Thin-type integral imaging method with an organic light emitting diode panel.
A thin and lensless two-dimensional (2D) to three-dimensional (3D) convertible display based on integral imaging using an organic light emitting diode (OLED) panel as a direct emissive light source is proposed with improved optical efficiency. A point light source array for 2D-3D convertible display is formed on the surface light source, i.e., the OLED panel. However, a blurring effect and color separation result from the finite (nonzero) size of point light sources since each point light source is generated by a pixel of the OLED panel. Simulation results for a blurring effect and color separation in terms of rays from a light source with finite size is presented. The proposed system has a thin structure and simple convertibility because it does not need any additional optical element to provide 2D-3D convertibility.


Identification and bioactivity of 3-epi-xestoaminol C isolated from the New Zealand brown alga Xiphophora chondrophylla.
We report here the bioassay-guided isolation of a new 1-deoxysphingoid, 3-epi-xestoaminol C (1), isolated from the New Zealand brown alga Xiphophora chondrophylla. This is the first report of a 1-deoxysphingoid from a brown alga. We describe the isolation and full structure elucidation of this compound, including its absolute configuration, along with its bioactivity against mycobacteria and mammalian cell lines and preliminary mechanism of action studies using yeast chemical genomics.


Daystay hamstring ACL reconstruction performed under regional anaesthesia.
Daycase ACL reconstruction is commonly performed under general anaesthesia with a patella tendon graft. We report our experience with hamstring reconstruction under regional anaesthesia. Over a 14-month period, 104 daycase arthroscopic ACL reconstructions were performed by one surgeon and one anaesthetist. All operations were performed under spinal anaesthesia with a femoral nerve block. Patients were discharged with oral analgesia, brace and a cryocuff. One hundred and two patients were prospectively evaluated with a visual analogue pain score (0-10) and a patient satisfaction questionnaire. Of these 102 patients, 101 (99%) were happy to be discharged on the same day. One patient was admitted from the daycase unit, and one patient was re-admitted. Patients were very satisfied with the pain relief provided. The mean visual analogue pain score was 1.0 at discharge, 1.8 in the middle of the first night, and 2.1 on the first post-op day. Patients experienced significantly more pain the day after surgery than the evening of surgery (p=0.04). We conclude that hamstring ACL reconstruction under regional anaesthesia is well tolerated by patients as a daycase procedure.


Should acute anterior dislocations of the shoulder be immobilized in external rotation? A cadaveric study.
The high recurrence rate associated with anterior shoulder dislocations may reflect inadequate healing of a Bankart lesion when the arm is immobilized in internal rotation. The effect of external rotation (ER) of the humerus on the glenoid-labrum contact of Bankart lesions was examined in 10 human cadaveric shoulders. The contact force between the glenoid labrum and the glenoid was measured in 60 degrees of internal rotation, neutral rotation, and 45 degrees of ER in 10 human cadaveric shoulders. No detectable contact force was found with the arm in internal rotation. The contact force increased as the arm passed through neutral rotation and reached a maximum at 45 degrees of ER. The contact force returned to 0 g when the arm was returned to neutral rotation. The mean contact force at 45 degrees of ER was 83.5 g. External rotation significantly increases the labrum-glenoid contact force and may influence the healing of a Bankart lesion.


Enterovirus 71 seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007.
During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. After informed consent was obtained, we enrolled preschool children, 6-15-year-old students, 16-50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3-5-year-old children, 31% (38/122) in 6-11-year-old primary school students, 45% (54/121) in 12-15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16-50-year-old people was having children in their families in addition to older age (p<0.001). Compared with the rates in 1997, 1999 and 2007, the rates in children were significantly lower in 2017. EV71 seropositive rates were very low, at 4% to 10%, in preschool children and not high, at 31%, in primary school students. Preschool children are highly susceptible and need EV71 vaccine most.


Detection of BRCA1/2 large genomic rearrangements in breast and ovarian cancer patients: an overview of the current methods.
Introduction: Currently, genetic testing of BRCA1/2 genes includes screening for single-nucleotide variants, small insertions/deletions, and copy number variations (CNVs). In fact, many studies document the involvement of BRCA1/2 gene rearrangements in genetic predisposition to breast and ovarian cancer. Large genomic rearrangements (LGRs) of BRCA1 may account for up to one-third of all disease-causing alterations in various populations, while LGRs in BRCA2 are less frequently observed. Areas covered: We aimed to present an overview of current technologies employed in molecular diagnosis of BRCA1/2 LGRs. The most relevant literature papers, showing the application of new strategies, were considered. Expert opinion: Currently, the progress of next-generation sequencing (NGS) technologies allows for the validation of new pipelines able to provide rapid and effective results, ensuring the sensitivity and specificity requested for the detection of BRCA1/2 LGRs. Multiplex ligation-dependent probe amplification remains the gold standard to confirm NGS CNVs results and to perform fast screening in families where a pathogenic rearrangement has been detected in a proband.


Quality of life and dyadic adjustment in oral cancer patients and their female partners.
The diagnosis of cancer affects not only the lives of patients, but also the lives of their family members. The purpose of this study was to examine the impact of oral cancer on quality of life (QoL), psychological distress and marital satisfaction in a sample of patients and their wives. Thirty-one men treated for oral cancer (mean time since diagnosis 3.7 years) and their female partners (n = 31) were assessed by questionnaires with regard to QoL (WHOQOL-BREF), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), quality of relationship (Dyadic Adjustment Scale, DAS) and physical complaints (EORTC QOL-H&N35). Quality of life was remarkably high in patients and their partners. In patients, lower QoL was associated with more physical complaints and higher levels of psychological distress (HADS), whereas in wives, QoL was found to be related to marital quality (DAS) and levels of distress. In couples with highly discrepant ratings of marital satisfaction, wives reported more psychological distress. The findings indicate that overall QoL is considerably high in patients treated for oral cancer and their partners living in stable relationships. Quality of life correlates stronger with the quality of relationship in spouses than in patients. Generally, marital satisfaction appears to be an important moderating factor regarding QoL and psychological distress.


A hierarchy of factors influence discontinuous gas exchange in the grasshopper Paracinema tricolor (Orthoptera: Acrididae).
The evolutionary origin and maintenance of discontinuous gas exchange (DGE) in tracheate arthropods are poorly understood and highly controversial. We investigated prioritization of abiotic factors in the gas exchange control cascade by examining oxygen, water and haemolymph pH regulation in the grasshopper Paracinema tricolor. Using a full-factorial design, grasshoppers were acclimated to hypoxic or hyperoxic (5% O2, 40% O2) gas conditions, or dehydrated or hydrated, whereafter their CO2 release was measured under a range of O2 and relative humidity (RH) conditions (5%, 21%, 40% O2 and 5%, 60%, 90% RH). DGE was significantly less common in grasshoppers acclimated to dehydrating conditions compared with the other acclimations (hypoxia, 98%; hyperoxia, 100%; hydrated, 100%; dehydrated, 67%). Acclimation to dehydrating conditions resulted in a significant decrease in haemolymph pH from 7.0±0.3 to 6.6±0.1 (mean ± s.d., P=0.018) and also significantly increased the open (O)-phase duration under 5% O2 treatment conditions (5% O2, 44.1±29.3 min; 40% O2, 15.8±8.0 min; 5% RH, 17.8±1.3 min; 60% RH, 24.0±9.7 min; 90% RH, 20.6±8.9 min). The observed acidosis could potentially explain the extension of the O-phase under low RH conditions, when it would perhaps seem more useful to reduce the O-phase to lower respiratory water loss. The results confirm that DGE occurrence and modulation are affected by multiple abiotic factors. A hierarchical framework for abiotic factors influencing DGE is proposed in which the following stressors are prioritized in decreasing order of importance: oxygen supply, CO2 excretion and pH modulation, oxidative damage protection and water savings.


Early Treatment of Acute Myocardial Infarction with Melatonin: Effects on MMP-9 and Adverse Cardiac Events.
Matrix metalloproteinase-9 (MMP-9) is crucial in tissue remodeling after an adverse cardiac event. In experimental studies, melatonin has been found to attenuate MMP-9 activation. The present study assessed the effects of systemic melatonin administration on the prognosis of patients with acute myocardial infarction (AMI) successfully treated with primary percutaneous coronary intervention, and to examine the effects on MMP-9 levels. We conducted a randomized controlled trial, enrolling patients who underwent primary percutaneous coronary intervention due to AMI. They were assigned to two groups for melatonin or placebo. The primary endpoint was a combined event of mortality and heart failure readmission at 2 years. The secondary endpoint was the levels of MMP-9 after the percutaneous coronary intervention. Ninety-four patients were enrolled, 45 in the melatonin group and 49 in the control group. At 2 years of follow-up, 13 (13.8%) patients suffered the primary endpoint (3 deaths and 10 readmissions due to heart failure), 3 patients in the melatonin group and 10 in the placebo group. The difference in the restricted mean survival time was 87.5 days (p = 0.02); HR = 0.3 (95% CI 0.08-1.08; p = 0.06); Log-rank test 0.04. After controlling for confounding variables, melatonin administration reduced MMP-9 levels to 90 ng/mL (95% CI 77.3-102.6). This pilot study demonstrated that compared to placebo, melatonin administration was associated with better outcomes in AMI patients undergoing primary percutaneous coronary intervention.


Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis.
Wnt/β-catenin signaling plays a major role in the development of the nervous system and contributes to neuronal plasticity. However, its role in myelination remains unclear. Here, we identify the Wnt/β-catenin pathway as an essential driver of myelin gene expression. The selective inhibition of Wnt components by small interfering RNA or dominant-negative forms blocks the expression of myelin protein zero (MPZ) and peripheral myelin protein 22 (PMP22) in mouse Schwann cells and proteolipid protein in mouse oligodendrocytes. Moreover, the activation of Wnt signaling by recombinant Wnt1 ligand increases by threefold the transcription of myelin genes and enhances the binding of β-catenin to T-cell factor/lymphoid-enhancer factor transcription factors present in the vicinity of the MPZ and PMP22 promoters. Most important, loss-of-function analyses in zebrafish embryos show, in vivo, a key role for Wnt/β-catenin signaling in the expression of myelin genes and in myelin sheath compaction, both in the peripheral and central nervous systems. Inhibition of Wnt/β-catenin signaling resulted in hypomyelination, without affecting Schwann cell and oligodendrocyte generation or axonal integrity. The present findings attribute to Wnt/β-catenin pathway components an essential role in myelin gene expression and myelinogenesis.


[The range of control of the afferent system of the flexor reflex].
The control processes caused by the action of electric inhibition of the nerve fibres and depolarized and hyperpolarized influences in the neurones structures of the spinal cord are discussed. Three typical bands of the amplitude control of motor apparatus in the multineuronic reflex ring are distinguished. The transmission of the action potentials in the battle control bands is carried out by the double way modulation. The first band is characterized by the most effective control with amplitude of the signal control in the limit of three thresholds. In the third band the transmission of information is possible in the inversion regime with unsteady polarity of the reflex movement. The second band unfits for the transmission of control commands.


A semi-parametric Bayesian approach for detection of gene expression heterosis with RNA-seq data.
Heterosis refers to the superior performance of a hybrid offspring over its two inbred parents. Although heterosis has been widely observed in agriculture, its molecular mechanism is not well studied. Recent advances in high-throughput genomic technologies such as RNA sequencing (RNA-seq) facilitate the investigation of heterosis at the gene expression level. However, it is challenging to identify genes exhibiting heterosis using RNA-seq data because high-dimension of hypotheses tests are conducted with limited sample size. Furthermore, detecting heterosis genes requires testing composite null hypotheses involving multiple mean expression levels instead of testing simple null hypotheses as in differential expression analysis. In this manuscript, we formulate a statistical model with parameters directly reflecting heterosis status, and develop a powerful test to detect heterosis genes. We employ a Bayesian framework where the RNA-seq count data are modeled through a Poisson-Gamma mixture with Dirichlet processes as priors for the distributions of the parameters of interest, the fold changes between each parent and the hybrid. Markov Chain Monte Carlo sampling with Gibbs algorithm is utilized to provide posterior inference to detect heterosis genes while controlling false discovery rate. Simulation results demonstrate that our proposed method outperformed other methods utilized to detect gene expression heterosis.


Proposal of novel structure for wide wavelength tuning in distributed Bragg reflector laser diode with single grating mirror.
We report a novel structure that is capable of wide wavelength tuning in the distributed Bragg reflector laser diode (DBR-LD) with a single grating mirror. This device's DBR section has two tuning elements, plasma, and heater tunings, which are implemented simultaneously on the top of a single waveguide by using an in-between dielectric layer. For the proposed structure, a three-dimensional thermal simulation was conducted. The results showed that the temperature profile within the waveguide is highly affected by the position of heater metal and thermal conductivity of the p-cladding layer. As a result, it is important to use a uniform temperature region in the DBR section for a wide tuning range and stable single-mode operation. For a 550-μm long DBR-LD with a 250-μm long DBR section, a tuning range of 26 nm (i.e., 7 nm for plasma tuning and 19 nm for heater tuning); an SMSR of more than 45 dB; and a peak power variation of less than ± 2.5 dB were obtained. From the comparisons of two DBR-LDs with only one tuning element, we confirmed that using the dielectric layer is a very effective way of achieving a wide tuning under the independent tuning operation.


Neuroform intracranial stenting for aneurysms using simple and multi-stent technique is associated with low risk of magnetic resonance diffusion-weighted imaging lesions.
Detection of procedural thromboembolism by diffusion-weighted magnetic resonance imaging (MR-DWI+) can help identify and mitigate endovascular risk factors. Data remain scant on procedural MR-DWI+ following the use of the Neuroform open-cell design stent in aneurysm embolization. We sought to evaluate the incidence of MR-DWI+ in Neuroform simple and multi-stent construct stenting for intracranial aneurysms in an attempt to delineate baseline risk and identify possible associated procedural factors. Seventy-six patients receiving 97 Neuroform stents in the treatment of intracranial aneurysm were identified from a prospective database and eligible for inclusion in the study. Diffusion-weighted magnetic resonance imaging (MR-DWI) was obtained in all patients within 48 hours of the procedure and reviewed for the presence of MR-DWI+ with patient records reviewed for analysis of factors predisposing to these lesions. Patients were treated with single-stent Neuroform constructs in 57 cases (73%) and multi-stent Neuroform constructs in 21 cases (27%). Y-stent technique was used in 16 cases. MR-DWI+ was identified in 7 of 78 cases (9.0%), with MR-DWI+ in 0 of 10 subarachnoid hemorrhage cases. No MR-DWI lesions led to a permanent neurological deficit at discharge. There was no MR-DWI+ in patients treated with Y-stenting or multi-stent Neuroform constructs. The only factor associated with ipsilateral MR-DWI+ was target aneurysm location on an arterial sidewall over bifurcation (P = .01). The Neuroform stent carries a very low risk of MR-DWI+ compared with its closed-cell design counterpart. Subarachnoid hemorrhage and deployment of multiple stents in the same anatomical region in configurations such as the Y-stent construct did not increase the risk of acute procedural thromboembolism.


The impact of abnormal muscle tone from hemiplegia on reclining wheelchair positioning: a sliding and pressure evaluation.
Little is known about the influence of existing muscle tone abnormality on the sitting posture of stroke patients in reclining wheelchairs. To investigate the impact of muscle tone abnormality from hemiplegia on the forward sliding and pressure of stroke patients while sitting in reclining wheelchairs. Experimental study. The Assistive Devices/Technology Center at the Rehabilitation Department of hospital. 14 able-bodied elders and nonambulatory elderly stroke patients with flaccid (N.=12) or spastic hemiplegia (N.=13) participated in this study. Of the 12 patients with flaccid hemiplegia, 8 suffered from left-sided hemiplegia and 4 from right-sided hemiplegia. Of the 13 patients with spastic hemiplegia, 6 suffered from left-sided hemiplegia and 7 from right-sided hemiplegia. We performed 3 reclining cycles in wheelchairs with conventional seats and V-shaped seats for each participant. The sliding along the backrest (BS) plane and the seat (SS) plane, mean sitting pressure (MP), and sacral peak pressure (SPP) of the participants were recorded. The Kruskal-Wallis test was used to compare the difference in BS, SS, MP, and SPP between able-bodied elders and stroke patients. The BS, SS, and SPP during repetitive reclining were generally greatest in flaccid hemiplegic participants, followed by spastic hemiplegic participants, and finally by able-bodied participants. There was no significant difference in MP among three subject groups on both conventional seats and V-shaped seats in most comparisons. Able-bodied participants' buttocks tended to slide forward on conventional seats but backward on V-shaped seats, whereas hemiplegic participants' buttocks slid forward on both seat types. Stroke patients with flaccid hemiplegia are the most vulnerable to sacral sitting and higher sacral pressure in reclining wheelchairs, followed by patients with spastic hemiplegia. There is a difference in the displacement pattern between participants with normal muscle tone and those with abnormal muscle tone during wheelchair positioning. People who have hemiplegia with spasticity do not have incremental forward sliding with repetitive reclining in the same way as those who have a flaccid hemiplegia. The findings are valuable for wheelchair prescription and caregiver education.


Partial characterization of polyphenol oxidase activity in raspberry fruits.
A partial characterization of polyphenol oxidase (PPO) activity in raspberry fruits is described. Two early cultivars harvested in May/June (Heritage and Autumm Bliss) and two late cultivars harvested in October-November (Ceva and Rubi) were analyzed for PPO activity. Stable and highly active PPO extracts were obtained using insoluble poly(vinylpyrrolidone) (PVP) and Triton X-100 in sodium phosphate, pH 7.0 buffer. Polyacrylamide gel electrophoresis of raspberry extracts under nondenaturing conditions resolved in one band (R(f)()(1) = 0.25). Raspberry PPO activity has pH optima of 8.0 and 5.5, both with catechol (0.1 M). Maximum activity was with D-catechin (catecholase activity), followed by p-coumaric acid (cresolase activity). Heritage raspberry also showed PPO activity toward 4-methylcatechol. Ceva and Autumm Bliss raspberries showed the higher PPO activity using catechol as substrate.


Sclerosing mesenteritis successfully treated with a TNF antagonist.
A 29-year-old female presented with intermittent nausea, vomiting, fevers, abdominal pain and fatigue. CT scans of the abdomen revealed inflammatory changes within the mesentery and small bowel. Histopathology of the mesentery and omentum showed chronic inflammation and fibrosis, supporting a diagnosis of sclerosing mesenteritis. Over the past 2 years, the patient suffered debilitating paroxysmal abdominal pain despite treatment with prednisone, azathioprine, sulfasalazine and narcotics. Additionally, she developed sacroiliitis diagnosed clinically and on radiographs. Intravenous infliximab (5 mg/kg intravenous) was initiated and continued every 6 weeks for 3 years. The patient has since had a dramatic improvement in her back and abdominal symptoms and has tapered off of prednisone, azathioprine and narcotics. Erythrocyte sedimentation rate, anaemia, leukocytosis and radiographic findings improved after initiation with infliximab. In conclusion, the authors report successfully treating sclerosing mesenteritis with sacroiliitis by the addition of infliximab. This may implicate a role for tumour necrosis factor α in disease pathogenesis.


Pestivirus and alphaherpesvirus infections in Swedish reindeer (Rangifer tarandus tarandus L.).
Herding semi-domesticated reindeer has economic and social value for Sami people in the northern territories of Fennoscandia. However, with the intensification of reindeer husbandry, interspecies transmission of pathogens between reindeer and domestic animals may become a problem, especially for countries such as Sweden, Norway, and Finland where pestivirus and alphaherpesvirus have been eradicated in domestic ruminants. This study, which included 1158 Swedish reindeer, showed relatively high prevalence of antibodies against bovine viral diarrhoea virus (BVDV) (32%) and bovine herpesvirus-1 (BoHV-1) (53%). Adult animals were more often seropositive for BVDV and BoHV-1 (50% and 78%, respectively) than were calves (18 and 11%, respectively). While the seroprevalence of alphaherpesvirus was similar in different herding districts, pestivirus seropositivity was highest in the South and diminished towards the North of the Swedish reindeer herding area. High correlation of the seropositivity against both pathogens at both individual and herd levels may indicate possible mutual synergetic effects and may be explained by the immunosuppressive nature of the viruses. While alphaherpesvirus seroprevalence was probably related to putative cervid herpesvirus 2 (CvHV-2), the pestivirus infecting reindeer remains undefined. The virus neutralisation test of reindeer sera using different pestivirus strains, revealed higher titres against Border disease virus strains like 137/4 (BDV-1) and Reindeer-1 (BDV-2) than against BVDV-1. However, the virus was not identified by real time RT-PCR in any of the samples (n=276) from seronegative reindeers. The study showed that pestivirus and alphaherpesvirus infections are endemic in the Swedish reindeer population.


Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.
Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies.


Prevalence of beta thalassemia carriers in India: a systematic review and meta-analysis.
A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a systematic review of the published studies and conduct a meta-analysis to determine the prevalence of beta thalassaemia carriers in India. A PubMed database search using keywords "beta thalassaemia AND India" identified 1088 articles of which 69 articles were included in the review. Studies using diagnostic tests and methods recommended by the International Council for Standardization in Haematology were used for calculation of pooled prevalence. Pooled prevalence was calculated using a random effects model using Review Manager version 5.3. Studies had screened five categories of populations, that is, the general population; tribal groups, communities not belonging to tribal groups, persons with anemia, and persons referred with a suspicion of hemoglobinopathy. This heterogeneity contributed to a high pooled prevalence of beta thalassemia carriers of 8.23% (95% CI 7.36-9.10). Sub-group analysis however yielded 3.74% (95% CI 2.52-4.97) pooled prevalence of beta thalassemia carriers in the general population. It was 4.6% (95% CI 3.2-6.2) among tribal groups. Quality of prevalence studies was limited by methodological issues including non-random sampling methods, heterogeneity of population types screened, and lack of use of recommended diagnostic cut-offs. Prevalence of beta thalassemia carriers was similar in tribal populations and the general population, indicating the need to further investigate the prevalence of beta thalassemia carriers in tribal groups.


Methamphetamine use and schizophrenia: a population-based cohort study in California.
Clinical investigators in Japan have long suggested that exposure to methamphetamine might cause a persistent schizophrenia-like psychosis. This possibility is discounted in the Western literature. To investigate the relationship between drug use and later schizophrenia, the authors conducted a large-scale cohort study of drug users initially free of persistent psychosis. A population-based cohort study was conducted using data from California inpatient hospital discharge records from 1990 through 2000. Patients with methamphetamine-related conditions (N=42,412) and those with other drug use disorders (cannabis, cocaine, alcohol, and opioids) were propensity score-matched to individuals with primary appendicitis who served as a population proxy comparison group; the methamphetamine cohort was also matched to the other drug cohorts. Cox modeling was used to estimate differences between matched groups in the rates of subsequent admission with schizophrenia diagnoses. The methamphetamine cohort had a significantly higher risk of schizophrenia than the appendicitis group (hazard ratio=9.37) and the cocaine, opioid, and alcohol groups (hazard ratios ranging from 1.46 to 2.81), but not significantly different from that of the cannabis group. The risk of schizophrenia was higher in all drug cohorts than in the appendicitis group. Study limitations include difficulty in confirming schizophrenia diagnoses independent of drug intoxication and the possibility of undetected schizophrenia predating drug exposure. The study's findings suggest that individuals with methamphetamine-related disorders have a higher risk of schizophrenia than those with other drug use disorders, with the exception of cannabis use disorders. The elevated risk in methamphetamine users may be explained by shared etiological mechanisms involved in the development of schizophrenia.


Elevated platelet activation in patients with atopic dermatitis and psoriasis: increased plasma levels of beta-thromboglobulin and platelet factor 4.
Beyond their role in hemostasis and thrombosis, platelets are important for modulating inflammatory reactions. Activated platelets play a role in the pathomechanism of inflammatory diseases such as asthma, but little is known about platelet activation in chronic skin inflammation, including atopic dermatitis (AD) and psoriasis. Furthermore, the relationship between platelet activation and disease severity is not understood. This work was performed to investigate plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) as platelet activation markers in patients with AD or psoriasis, and to determine the relationships between these markers and disease severity. Plasma levels of beta-TG and PF4 were measured by enzyme-linked immunoassay in 22 healthy controls, 44 patients with AD, and 16 patients with psoriasis. The relationships between these markers and the scoring AD (SCORAD) index, blood eosinophilia, serum IgE and serum lactate dehydrogenase were investigated in AD patients, and relationships with the psoriasis area and severity index (PASI) score were examined in psoriatic patients. Plasma beta-TG and PF4 levels were significantly higher in patients with AD or psoriasis compared with healthy controls. beta-TG and PF4 levels correlated with the SCORAD index, and PF4 levels correlated with PASI scores. Elevated beta-TG and PF4 levels were significantly reduced after treatments. Our results show that blood platelets are activated in patients with AD or psoriasis, suggesting that activated platelets play a role in the pathomechanism of chronic skin inflammation. Furthermore, plasma beta-TG and PF4 may be markers for the severity of AD and psoriasis.


Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.
Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.


Normalization of the psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in Turkey.
To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic encephalopathy (MHE) among Turkish patients with liver cirrhosis. One hundred and eighty-five healthy subjects and sixty patients with liver cirrhosis without overt hepatic encephalopathy were included in the study. All subjects underwent psychometric tests, which include number connection test-A and B (NCT-A/B), serial dotting test (DST), line drawing test (LDT), and digit symbol test (DST) in the same day. The variables that affected the results of the test were included in the multiple linear regression models and formulas were constructed to predict the expected results for each tests. The results of all PHES tests, except the LDT in the cirrhotic group were significantly different than center of gravity (CG) (P < 0,001). The score of PHES in the cirrhotic group was -2,18 ± 3,3 (median -2; range: 11 to +4), significantly lower than CG (-0.31 ± 2.18 [median, 0; range, -8 to +5]) (P < 0.001). the cutoff of PHES was set -4 point. Therefore, 19 of the 60 cirrhotic patients were diagnosed with MHE (31.6%). Among the patients with MHE, 11 (11/45, 24,4%) had Child-Pugh classification (CTP) A and 8 (8/15, 53.3%) had CTP B. No differences in age and education years were found between the MHE and non-MHE groups (P > 0.05). Turkish PHES normograms have been developed for detecting patients with MHE. Future multicenter national studies are needed to validate widely applicable norms.


Effects of saponin extracts on air emissions from steers.
A series of experiments were conducted to quantify the effects of saponin extracts from Quillaja saponaria Molina (QS), Yucca schidigera Roezl ex Ortgies (YS), and Camellia sinensis (L.) Kuntze (TS) on gaseous emissions from steers (Bos taurus). During Exp. 1, a control diet [C1, corn (Zea mays L.) and corn silage basal diet] was compared with YS1 (C1 + 0.64% dietary DM of YS) and QS1 (C1 + 1.5% dietary DM of QS), with 4 replicates per treatment. During Exp. 2, the control diet (C2, corn and corn silage basal diet) was compared with TS2 (C2 + 0.25% dietary DM of TS). Product inclusion levels were established to provide the same concentration of saponin compounds across studies for Exp. 1 and 2. Experiment 3 compared C3 (corn and corn silage basal diet), QS3 (C3 + 1.5% QS), YS3 (C3 + 1.5% YS), and TS3 (C3 + 0.5% TS). Holstein steers (n = 12) at initial BW of 354 ± 10 kg (Exp. 1), 429 ± 10 kg (Exp. 2), 382 ± 16 kg (Period 1, Exp. 3) and 400 ± 12 kg (Period 2, Exp. 3) were individually housed in environmental rooms for 22 d per study. Gaseous emissions including methane (CH(4)), ammonia (NH(3)), and nitrous oxide (N(2)O) were monitored in room exhaust air. No differences in DMI (7.54 ± 0.09 kg) and ADG (1.16 ± 0.19 kg) were observed in Exp. 1 (P > 0.05). Adding TS2 to the diet improved DMI in Exp. 2 (8.94 kg in TS2 vs. 8.53 in C2; P < 0.01), whereas ADG was not affected by diet. During Exp. 3, steers fed the TS3 diet ate less (6.36 kg/d) and gained less BW (0.31 kg/d) compared with the other 3 treatments. Saponin inclusion did not alter daily CH(4) emission per unit DMI (13.17, 10.90, and 13.21 g/kg DMI, for Exp. 1, 2, and 3, respectively). Emissions of NH(3) per unit N intake were not affected by diets in Exp. 1 (134.89 mg/g N consumed) and Exp. 3 (134.99 mg/g N consumed). Feeding TS2 reduced NH(3) emission per unit of N consumed by 30% compared with C2 (P < 0.01). Feeding up to 0.5% of TS failed to reduce CH(4) emissions without impairing steer growth. Nitrous oxide emissions were not affected by TS addition. Air emissions were not affected by feeding steers with up to 1.5% YS. Feeding 1.5% QS to steers had an inconsistent effect upon NH(3) emissions and no other effects upon gaseous emissions were seen from steers.


Compensatory function of Pyk2 protein in the promotion of focal adhesion kinase (FAK)-null mammary cancer stem cell tumorigenicity and metastatic activity.
Mammary cancer stem cells (MaCSCs) have been identified as a rare population of cells capable of self-renewal to drive mammary tumorigenesis and metastasis. Nevertheless, relatively little is known about the intracellular signaling pathways regulating self-renewal and metastatic activities of MaCSCs in vivo. Using a recently developed breast cancer mouse model with focal adhesion kinase (FAK) deletion in mammary tumor cells (MFCKO-MT mice), here we present evidence suggesting a compensatory function of Pyk2, a FAK-related kinase, in the regulation of MaCSCs and metastasis in these mice. Increased expression of Pyk2 was found selectively in pulmonary metastatic nodules of MFCKO-MT mice, and its inhibition significantly reduced mammary tumor development and metastasis in these mice. Consistent with the idea of metastasis driven by MaCSCs, we detected selective up-regulation of Pyk2 in MaCSCs, but not bulk mammary tumor cells, of primary tumors developed in MFCKO-MT mice. We further showed that inhibition of Pyk2 in FAK-null MaCSCs significantly decreased their tumorsphere formation and migration in vitro as well as self-renewal, tumorigenicity, and metastatic activity in vivo. Last, we identified PI3K/Akt signaling as a major mediator of FAK regulation of MaCSCs as well as a target for the compensatory function of Pyk2 in FAK-null MaCSCs. Together, these results further advance our understanding of FAK and its related tyrosine kinase Pyk2 in regulation of MaCSCs in breast cancer and suggest that pharmaceutically targeting these kinases may hold promise as a novel treatment for the disease by targeting and eradicating MaCSCs.


Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration.
After a nascent chain of a membrane protein emerges from the ribosomal tunnel, the protein is integrated into the cell membrane. This process is controlled by a series of proteinaceous molecular devices, such as signal recognition particles and Sec translocons. In addition to these proteins, we discovered two endogenous components regulating membrane protein integration in the inner membrane of Escherichia coli. The integration is blocked by diacylglycerol (DAG), whereas the blocking is relieved by a glycolipid named membrane protein integrase (MPIase). Here, we investigated the influence of these integration-blocking and integration-promoting factors on the physicochemical properties of membrane lipids via solid-state NMR and fluorescence measurements. These factors did not have destructive effects on membrane morphology because the membrane maintained its lamellar structure and did not fuse in the presence of DAG and/or MPIase at their effective concentrations. We next focused on membrane flexibility. DAG did not affect the mobility of the membrane surface, whereas the sugar chain in MPIase was highly mobile and enhanced the flexibility of membrane lipid headgroups. Comparison with a synthetic MPIase analog revealed the effects of the long sugar chain on membrane properties. The acyl chain order inside the membrane was increased by DAG, whereas the increase was cancelled by the addition of MPIase. MPIase also loosened the membrane lipid packing. Focusing on the transbilayer movement, MPIase reduced the rapid flip-flop motion of DAG. On the other hand, MPIase could not compensate for the diminished lateral diffusion by DAG. These results suggest that by manipulating the membrane lipids dynamics, DAG inhibits the protein from contacting the inner membrane, whereas the flexible long sugar chain of MPIase increases the opportunity for interaction between the membrane and the protein, leading to membrane integration of the newly formed protein.


Palmitate activation and esterification in microsomal fractions of rat liver.
Palmitoyl-CoA synthetase activity in the microsomal fraction of rat liver was measured directly by palmitoyl-CoA production, and indirectly by converting the palmitoyl-CoA into palmitoylcarnitine under optimum conditions. Even in the latter system, palmitoyl-CoA accumulated. The rate of palmitoyl-CoA hydrolysis and the inhibition of palmitoyl-CoA synthetase by palmitoyl-CoA were each estimated to be less than 10% of the maximum rate of palmitoyl-CoA production. The concentration of palmitoyl-CoA present in the assay systems used for measuring palmitate esterification to glycerol phosphate and the activity of palmitoyl-CoA synthetase by using the carnitine-linked determination were measured. These concentrations were not altered by the addition of glycerol phosphate, or of carnitine plus carnitine palmitoyltransferase. The relationship between the activity of palmitoyl-CoA synthetase and the rate of glycerolipid synthesis was investigated. The latter activity was measured by using palmitoyl-CoA generated from palmitate, palmitoyl--AMP or palmitoylcarnitine. It is concluded that, at optimum substrate concentrations, the activity of glycerol phosphate acyltransferase is rate-limiting in the synthesis of phosphatidate by rat liver microsomal fractions. The implications of these results in the measurement of palmitoyl-CoA synthetase and in the control of glycerolipid synthesis are discussed.


Angioscopic coronary macromorphology in patients with acute coronary disorders.
To investigate the pathogenesis of acute coronary disorders and to clarify what type of plaque precedes these disorders, percutaneous transluminal coronary angioscopy, by means of a new angioscope, was carried out during catheterisation in 100 consecutive patients anatomically suitable for such investigations. The quality of the angioscopic image was good enough for analysis in 84 patients (14 with acute myocardial infarction [within 8 h of onset], 16 with recent myocardial infarction [3 days-2 months since onset], 24 with old myocardial infarctions, 10 with unstable angina, and 20 with stable angina). Thrombi were observed in most patients with acute coronary disorders (all 14 with acute myocardial infarction, 9 of 10 with unstable angina). Occlusive thrombi were more common in patients with acute myocardial infarction than in those with unstable angina (11 [79%] vs 1 [10%]; p less than 0.001), whereas mural (non-occlusive) thrombi were more common in the unstable angina than in the acute myocardial infarction group (8 [80%] vs 3 [21%]; p less than 0.001). Xanthomatous ulcerated plaques or ragged irregular surfaces were seen in patients with acute coronary disorders and in those with recent myocardial infarction. Xanthomatous plaques were more common in patients with acute coronary disorders (50%) than in those with stable angina (15%) or old myocardial infarction (8%). By contrast white and smooth plaques were seen in cases of stable angina and old myocardial infarction. Angioscopy could display the intracoronary lumen more precisely than could coronary arteriography. This angioscopic study suggested that, although a thrombus overlying a rupture in the lining of the plaque was common in both unstable angina and acute myocardial infarction, the character of the thrombus may differ between these disorders, and lipid-rich xanthomatous plaque may precede rupture.


Cell compatibility of fibrin sealants: in vitro study with cells involved in soft tissue repair.
Fibrin sealants can be used to support tissue regeneration or as vehicles for delivery of cells in tissue engineering. Differences in the composition of fibrin sealants, however, could determine the success of such applications. The results presented in this article show clear differences between Fibrin sealant A (FS A) clots and Fibrin sealant B (FS B) clots with respect to their compatibility with primary human cells involved in soft tissue repair. FS A clots, which are characterized by a physiological coarse fibrin structure, promoted attachment, spreading, and proliferation of keratinocytes, fibroblasts, and endothelial cells. In contrast, FS B clots displaying a fine to medium clot structure failed to support spreading of all three cell types. Adhesion of keratinocytes was decreased on FS B clots compared to FS A clots after 3 h incubation, whereas number of attached fibroblasts and endothelial cells was initially comparable between the two fibrin sealants. However, all three cell types proliferated on FS A clots but no sustained proliferation was detected on FS B clots. We further demonstrate that the observed differences between FS A and B clots are partly based upon 1 M sodium chloride extractable constituents, like thrombin, and partly on nonextractable constituents or the fibrin structure. In conclusion, our in vitro results demonstrate that FS A clots serve as a provisional matrix that encourages adhesion and growth of keratinocytes, fibroblasts, and endothelial cells. Therefore, FS A seems to be well suited for applications in tissue engineering.


A mitochondrial RNAi screen defines cellular bioenergetic determinants and identifies an adenylate kinase as a key regulator of ATP levels.
Altered cellular bioenergetics and mitochondrial function are major features of several diseases, including cancer, diabetes, and neurodegenerative disorders. Given this important link to human health, we sought to define proteins within mitochondria that are critical for maintaining homeostatic ATP levels. We screened an RNAi library targeting >1,000 nuclear-encoded genes whose protein products localize to the mitochondria in multiple metabolic conditions in order to examine their effects on cellular ATP levels. We identified a mechanism by which electron transport chain (ETC) perturbation under glycolytic conditions increased ATP production through enhanced glycolytic flux, thereby highlighting the cellular potential for metabolic plasticity. Additionally, we identified a mitochondrial adenylate kinase (AK4) that regulates cellular ATP levels and AMPK signaling and whose expression significantly correlates with glioma patient survival. This study maps the bioenergetic landscape of >1,000 mitochondrial proteins in the context of varied metabolic substrates and begins to link key metabolic genes with clinical outcome.


[Analgesia in critical cares].
Pain is a problem in critically ill patients. The diagnosis of the intensity of is more simple when the patient is conscious (using ad hoc scales) than in unconscious or sedated patients. In these cases the study of the physiological responses to pain can be the best way of pain monitoring. The pain management in ICU patients must be a priority of the treatment. Opioids are the pharmacological group more advisable for pain treatment in ICU. Intravenous administration in continuous perfusion is the more accepted route for this treatment. The use of other routes (subcutaneous, intramuscular, oral, intramuscular and transcutaneous) must be restricted due to the potential lack of activity for the fragment variability of biodisponibility of drugs. Complementary to the intravenous administration opioids are the use of bolus or the supplementation with non-opioids analgesics. Morphine, fentanyl, remifentanyl and tramadole are the opioids more used critical ill patients. Ketamine, metamizole and acetaminophen must be considered as non-opioid alternative therapeutic. NSAIDS are non recommended for this group of patients.


Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease.
Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.


Altered glutamate cysteine ligase activity in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.
Reductions in glutathione (GSH) levels have been shown to be associated with aging and the pathogenesis of a variety of diseases, including systemic lupus erythematosus (SLE). Glutamate cysteine ligase (GCL) catalyzes the first and rate-limiting step of GSH synthesis. In order to appraise the correlation between oxidative stress and the severity and activity of SLE, GSH, oxidized GSH (GSSG) and thioredoxin (TRX) concentrations and the enzymatic activity levels of GCL in peripheral blood mononuclear cells (PBMCs) from patients with SLE and healthy controls were studied. In patients with SLE, the levels of GCL activity and GSH decreased, while TRX and GSSG levels increased when compared with those in the healthy controls. GSH concentrations and GCL activity levels negatively correlated with the SLE disease activity index and erythrocyte sedimentation rate. Furthermore, patients with SLE and nephritis had lower levels of GSH and GCL activity and higher levels of TRX and GSSG compared with those in SLE patients without nephritis. Therefore, the results of the present study indicate that insufficient levels of GSH and GCL activity in PBMCs may contribute to the pathogenesis of SLE.


A dual action of alpha-lipoic acid in the brain: an electrophysiological evaluation.
Oxidative stress causes metabolic and structural abnormalities during reperfusion. In an animal model of electrophysiological evaluation of cerebral ischemia-reperfusion, alpha-lipoic acid effect on the oxidative stress was studied by mean absolute amplitude of EEG spectra evaluation. The left carotideal infusion of 3.03 mM alpha-lipoic acid in Wistar rats after cerebral ischemia and reperfusion caused initial reduction and partial final recuperation of the various EEG spectral frequency mean absolute amplitudes (p<0.05). The left intracarotideal infusion of 6.06 mM alpha-lipoic acid significantly reverted the induced depression of mean absolute amplitude of theta and delta spectra. Nevertheless there was an increasing pattern of ischemia demonstrated by mean absolute amplitude depression of almost all EEG spectra with 60.6 mM alpha-lipoic acid infusion. These observations suggest that, depending on the administered concentration, alpha-lipoic acid may act in a dual way, protecting from ischemia at lower concentrations and worsening this process at higher doses.


[Cognitive deterioration in multiple sclerosis].
Amongst the varied symptomology of multiple sclerosis is to be found the alteration of higher functions (cognitive deficit), which has considerable repercussions on the quality of life of patients. The old descriptions of the disease rarely differentiate cognitive affectation from the more general category of "mental symptoms", which also includes a broad range of affective disorders. Towards 1960 neuropsychological tests began to be employed, and it was from the 1970s onwards that a clear distinction was drawn between deterioration of the higher functions and psycho-affective aspects in the disease. The pattern of cognitive deterioration in patients with multiple sclerosis is not uniform. During the initial phases of the disease it is, in general, light and it has an insidious start, although inter-individual variability is wide, depending on the predominant pathological alterations in the lesions and on their number and localisation. In more severe cases, it is possible to include within the debatable term of subcortical dementia, intellectual slowness, problems of attention, alterations in abstract reasoning, shortcomings in the resolution of problems and memory dysfunction. It is an almost invariable complication of the advanced stages of the disease, since the lesions characterised by axonal loss affect broad areas of white matter, which determines the deafferentation of several areas of cortical association. There does not appear to be any correlation between cognitive deterioration and the variables of the disease considered in an independent way, such as demographic data, clinical course, alterations of mood, consumption of medicines or fatigue. Although, evidently, the disease's progressive secondary forms of greater duration and the accumulation of lesions are what present the greatest deterioration. With present-day techniques of neuroimaging it has been possible to show a correlation between cognitive deterioration and the existence of an increase in ventricular size, periventricular lesions and atrophy of the callous body.


Birth weight and cognitive ability in childhood among siblings and nonsiblings.
The purpose of this work was to examine whether the positive association between birth weight and childhood cognitive ability is seen within siblings from the same family, as well as between nonsiblings, and to determine whether these associations vary with age. We compared the association of birth weight with cognitive ability measured at ages 5 to 6, 7 to 9, and 11 to 12 years among a total of 5402 children from different families with that among 2236 to 3083 sibships from the National Longitudinal Study of Youth 1979-Children. In the whole cohort, there were positive associations between birth weight and cognitive ability at all ages, with the association increasing with age from a 0.81-point increase at ages 5 to 6 years to 1.30 and 1.44 points at ages 7 to 9 and 11 to 12 years, respectively, per 1 SD of gestational age- and gender-adjusted birth weight z score. With adjustment for covariates, there was marked attenuation of these associations. Mean differences were 0.28 points in children aged 5 to 6 years, 0.67 points in those aged 7 to 9 years, and 0.52 points in those aged 11 to 12 years after adjusting for child's gender, race or ethnicity, year of birth, and age at test; maternal age, height, parity, education, smoking during pregnancy, and cognitive ability; and household income. Our family-based analyses that separated within- and between-family effects found that the between-family associations were much stronger than the within-family associations. However, adjustment for potential confounders attenuated the between-family associations, and there was no evidence for a difference in association comparing the between- and within-family associations. In these data, the positive association between birth weight and childhood cognitive ability at ages 5 to 12 years is explained largely by family characteristics rather than a specific intrauterine effect.


In vitro availability of iron and zinc: effects of the type, concentration and fractions of digestion products of the protein.
An in vitro dialysis method was employed to determine the effect on the Fe and Zn absorption of the type (beef, pork and soyabean) and the amount (10 and 30 g/kg) of protein present. In addition, the effects of low- and high-molecular-weight (LMW and HMW respectively) digestion products were investigated. After in vitro digestion and dialysis a lower percentage of N, Fe and Zn was found in the LMW fractions from beef, pork and soyabean proteins when the protein level was increased from 10 to 30 g/kg; the higher level of protein being associated with a lower percentage of hydrolysed protein. The highest percentage levels of intrinsic Fe were always found in the HMW fractions, independent of the type and the level of proteins studied, while in the case of Zn, both HMW and LMW fractions gave similar values. An interaction was found between inorganic Zn and non-haem-Fe. The addition of inorganic Zn (10 micrograms/ml) caused a significant decrease in the in vitro availability of Fe from soyabean protein, while it did not affect the dialysability of intrinsic Fe from beef and pork proteins. Our results showed that the type and the level of the protein had a positive effect on the dialysability of extrinsic Fe. We postulate that the effect of a protein on the absorption of extrinsic Fe could be accounted for by free amino acids and/or small peptides released during the digestion process and also by the undigested or partially-digested HMW fractions of hydrolysed proteins which could play a fundamental role in the availability of this essential element.


[Suppression of epileptiform activity by micropolarizing brain structures].
Penicillin administration elicited epileptiform responses whereas micropolarization (MCP) affected the epileptogenic foci in cats with indwelled electrodes and chemotrodes. Three types of experimental epilepsy models were obtained: focal petit mal seizures, adversive, and grand mal seizures. The MCP of amygdala and caudate nucleus completely suppressed all three types of seizures whereas MCP of hippocampus enhanced the pathology. Two mechanisms of seizure suppression seem to exist: the inhibitory and the activating ones.


Challenges and emerging opportunities for the HIV prevention, treatment and care cascade in men who have sex with men in Asia Pacific.
In Asia Pacific, most countries have expanded HIV treatment guidelines to include all those with HIV infection and adopted antiretroviral treatment for prevention (TFP) as a blanket strategy for HIV control. Although the overall epidemic development associated with this focus is positive, the HIV epidemic in men who have sex with men (MSM) is continuing unperturbed without any signs of decline or reversal. This raises doubt about whether TFP as a blanket HIV prevention policy is the right approach. This paper reviews currently available biomedical HIV prevention strategies, national HIV prevention policies and guidelines from selected countries and published data on the HIV cascade in MSM. No evidence for efficacy of TFP in protecting MSM from HIV infection was found. The rationale for this approach is based on assumptions about biological plausibility and external validity of latency-based efficacy found in heterosexual couples. This is different from the route and timing of HIV transmission in MSM. New HIV infections in MSM principally occur in chains of acutely HIV-infected highly sexually active young men, in whom acquisition and transmission are correlated in space and time. By the time TFP renders its effects, most new HIV infections in MSM will have already occurred. On a global level, less than 6% of all reports regarding the HIV care cascade from 1990 to 2016 included MSM, and only 2.3% concerned MSM in low/middle-income countries. Only one report originated from Asia Pacific. Generally, HIV cascade data in MSM show a sobering picture of TFP in engaging and retaining MSM along the continuum. Widening the cascade with a preventive extension, including pre-exposure prophylaxis, the first proven efficacious and only biomedical HIV prevention strategy in MSM, will be instrumental in achieving HIV epidemic control in this group.


[Fetal development of the omasum of cattle (Bos taurus)].
Structures characteristic of the omasum are already present by the third month of development. The fetal omasal laminae exhibit their typical arrangement (1434243414). Muscle fibers from the lamina circularis also extend into the first through third order laminae at this stage. Conical projections and small secondary papillae begin to appear on the laminae as the fetus ages. The lamina muscularis mucosae can be found in all of the laminae by the fourth to fifth month of development. The cuboidal to columnar epithelium of the stratum basale remains largely unaltered throughout the course of fetal development, whereas the stratum superficiale is subjected to a continuous series of changes. Superficial cell layers increase and the glycogen content of the epithelial cells fluctuates significantly.


CommonsenseVIS: Visualizing and Understanding Commonsense Reasoning Capabilities of Natural Language Models.
Recently, large pretrained language models have achieved compelling performance on commonsense benchmarks. Nevertheless, it is unclear what commonsense knowledge the models learn and whether they solely exploit spurious patterns. Feature attributions are popular explainability techniques that identify important input concepts for model outputs. However, commonsense knowledge tends to be implicit and rarely explicitly presented in inputs. These methods cannot infer models' implicit reasoning over mentioned concepts. We present CommonsenseVIS, a visual explanatory system that utilizes external commonsense knowledge bases to contextualize model behavior for commonsense question-answering. Specifically, we extract relevant commonsense knowledge in inputs as references to align model behavior with human knowledge. Our system features multi-level visualization and interactive model probing and editing for different concepts and their underlying relations. Through a user study, we show that CommonsenseVIS helps NLP experts conduct a systematic and scalable visual analysis of models' relational reasoning over concepts in different situations.


Induction of mitochondrial dysfunction in patients under cardiopulmonary by-pass: preliminary results.
Cardiac surgery is often performed by cardiopulmonary by-pass (CPB), generally associated with organ dysfunction. The aim of this work was to determine if and how this phenomenon is related to mitochondrial damage. To this purpose, the effect of the addition of serum from CPB patients to human fibroblasts cultures on mitochondrial respiratory chain and oxidative phosphorylation (OXPHOS) activities was investigated. Serum samples of five patients were obtained before (pre-CPB) and after 6 h CPB weaning (CPB). Mitochondrial OXPHOS activities were examined by polarographic and spectrophotometric assays, and reactive oxygen species (ROS) production was measured by a spectrofluorimeter. Addition of CPB serum to fibroblasts determined a decrease of mitochondrial oxygen consumption due to an inhibition of mitochondrial respiratory chain and some OXPHOS enzymes activities. This inhibition seems to be mainly related to a reduced activity of complex I. Our data represent the first translational research evidence showing that CPB determines mitochondrial dysfunction which leads to impairment of OXPHOX activities and to an increase in ROS production, compromising tissue bioenergetic efficiency.


Prophylactic mirtazapine reduces intrathecal morphine-induced pruritus.
Activation of the serotonergic system is an important factor in the pathogenesis of intrathecal morphine-induced pruritus. Mirtazapine is a new antidepressant that selectively blocks 5-HT(2) and 5-HT(3) receptors. We therefore tested the hypothesis that preoperative mirtazapine would reduce the incidence of intrathecal morphine-induced pruritus. One hundred and ten ASA I patients undergoing lower limb surgery under spinal anaesthesia were randomly allocated into two equal groups and received either mirtazapine 30 mg or an orally disintegrating placebo tablet 1 h before operation in a prospective, double-blinded trial. All patients received an intrathecal injection of 15 mg of 0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. The occurrence and the severity of pruritus were assessed at 3, 6, 9, 12, and 24 h after intrathecal morphine. Pruritus was significantly more frequent in the placebo group compared with the mirtazapine group (75% vs 52%, respectively; P=0.0245). The time to onset of pruritus in the two groups was also significantly different. The patients who experienced pruritus in the placebo group had a faster onset time than that in the mirtazapine group [mean (sd): 3.2 (0.8) vs 7.2 (4.1) h, P<0.0001]. Mirtazapine premedication prevents pruritus induced by intrathecal morphine in patients undergoing lower limb surgery with spinal anaesthesia.


[Mechanisms of serotonin effect on motility of ileocaecal zone in alert rabbits].
I.V. administration of serotonin (2 mg kg(-1)) to alert rabbits changed the ileal, caecal, and colon motility including excitatory and inhibitory components. Initial rise of contractile activity was quickly replaced by its diminishing followed by a longer enhancement of the motility, and then by the final, inhibitory, phase. Under blockade of beta1- and beta2-adrenoreceptors with propranolol inhibition of ileal and caecal contractile activity with serotonin was preserved, the effect of circulating catecholamines on beta-adrenoreceptors of smooth muscle cells seems to be excluded as a cause of the serotonin inhibitory effect. In conditions of blockade of pre- and postsynaptic alpha-adrenoreceptors with phentolamine, there was no significant diminishing of the contractile activity in the ileo-caecal zone below the initial level induced by serotonin in control experiments. Intensification of the ileo-caecal zone contractile activity under the effect of serotonin persisted in conditions of blockade of muscarinic cholinoreceptors and was proceeding with participation of non-cholinergic excitatory mechanism.


The use of Escherichia coli total antigens as a complementary approach to address seropositivity to Leishmania antigens in canine leishmaniosis.
Canine leishmaniosis (CanL) is a major veterinary concern and a public health issue. Serological data are essential for disease management. Several antigens used in serological assays have specificity related problems preventing relevant seropositivity values establishment. Herein we report significant seropositivity level disparity in a study cohort with 384 dogs from eight countries, for antigens traditionally used in CanL - soluble promastigote Leishmania antigens (SPLA) and K39 recombinant protein (rK39): 43·8 and 2·9% for SPLA and rK39, respectively. To better understand the reasons for this disparity, CanL-associated serological response was characterized using, for complement serological evaluation, a ubiquitous antigen - soluble Escherichia coli antigens (SECAs). Using cohorts of CanL dogs and dogs without clinical evidences of CanL from non-endemic regions of Portugal, the serological response of CanL animals followed specific trend of seropositivity rK39 > SPLA > SECA absent in non-diseased animals. Using receiver operating characteristic curve analysis, these characteristic trends were converted in ratios, SPLA/SECA, rK39/SECA and rK39/SPLA, that presented high predictive for discriminating the CanL cohort that was potentiated when applied in a scoring system involving positivity to four out of five predictors (rK39, SPLA, SPLA/SECA, rK39/SECA and rK39/SPLA). In fact, this approach discriminated CanL with similar sensitivity/specificity as reference antigens, diminishing seropositivity in European cohort to 1·8%. Ultimately, non-related antigens like SECA and seropositivity ratios between antigens enable different perspectives into serological data focusing on the search of characteristic serological signatures and not simple absolute serology values contributing to comprehensive serological status characterization.


Towards a Digital Lean Hospital: Concept for a Digital Patient Board and Its Integration with a Hospital Information System.
Lean management applied to healthcare aims at creating maximum value for patients by reducing waste and waits. It puts the patient's needs center stage, emphasizes employee involvement and continuous improvement. To realize this, visual tools such as the huddle board or the patient board are implemented in hospital wards. The boards are currently realized by whiteboards or flipcharts, which leads to duplicated data entries and loss of information. The objective of this work is to introduce a concept for digitalizing the patient board and integrate with a hospital information system (HIS) for improved data availability. Data on appointments, personnel planning and master patient data can be directly accessed from the HIS database. A digital patient board has several benefits: data can be collected from information systems, making it obsolete to record information several times. Even more functionalities, in particular, those supporting the communication between a patient and a healthcare team can be included by means of a digital board which improves patient involvement.


A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells.
Aspirin, one of the most widely used non-steroidal anti-inflammatory drugs, has extensively studied effects on the cardiovascular system. To reveal further pleiotropic, beneficial effects of aspirin on a number of pro- and anti-inflammatory microglial mechanisms, we performed morphometric and functional studies relating to phagocytosis, pro- and anti-inflammatory cytokine production (IL-1β, tumor necrosis factor-α (TNF-α) and IL-10, respectively) and analyzed the expression of a number of inflammation-related genes, including those related to the above functions, in pure microglial cells. We examined the effects of aspirin (0.1mM and 1mM) in unchallenged (control) and bacterial lipopolysaccharide (LPS)-challenged secondary microglial cultures. Aspirin affected microglial morphology and functions in a dose-dependent manner as it inhibited LPS-elicited microglial activation by promoting ramification and the inhibition of phagocytosis in both concentrations. Remarkably, aspirin strongly reduced the pro-inflammatory IL-1β and TNF-α production, while it increased the anti-inflammatory IL-10 level in LPS-challenged cells. Moreover, aspirin differentially regulated the expression of a number of inflammation-related genes as it downregulated such pro-inflammatory genes as Nos2, Kng1, IL1β, Ptgs2 or Ccr1, while it upregulated some anti-inflammatory genes such as IL10, Csf2, Cxcl1, Ccl5 or Tgfb1. Thus, the use of aspirin could be beneficial for the prophylaxis of certain neurodegenerative disorders as it effectively ameliorates inflammation in the brain.


Regulation of the WNT-CTNNB1 signaling pathway by severe fever with thrombocytopenia syndrome virus in a cap-snatching manner.
The segmented negative-strand RNA viruses (sNSVs) include highly pathogenic human and animal viruses such as Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and influenza A virus (IAV). One of the conserved mechanisms at the stage of genome transcription of sNSVs is the cap-snatching process, providing druggable targets for the development of antivirals. SFTSV is an emerging tick-borne sNSV that causes severe hemorrhagic fever with a high fatality rate of 12%-50%. Here, we determined the correlation between death outcome and downregulation of the WNT-CTNNB1 signaling pathway through transcriptomic analysis of blood samples collected from SFTS patients. We further demonstrated that SFTSV affected this pathway by downregulating the mRNA levels of a series of pathway-related genes, including CTNNB1. Loss-of-function mutations or inhibitors targeting SFTSV cap-snatching activity effectively alleviated the inhibition of the WNT-CTNNB1 signaling pathway. Exogenous activation of the WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway reduced SFTSV replication. Treatment with a WNT-CTNNB1 signaling pathway inhibitor attenuated viral replication and decreased fatality in mice. Notably, downregulation of the WNT-CTNNB1 signaling pathway was also observed for other sNSVs, including LASV and IAV. These results suggested that RNAs related to the WNT-CTNNB1 signaling pathway might be utilized as a primer "pool" in a cap-snatching manner for viral transcription, which provides effective targets for the development of broad-spectrum antivirals against sNSVs.IMPORTANCEOne of the conserved mechanisms at the stage of genome transcription of segmented negative-strand RNA viruses (sNSVs) is the cap-snatching process, which is vital for sNSVs transcription and provides drugable targets for the development of antivirals. However, the specificity of RNAs snatched by sNSV is still unclear. By transcriptomics analysis of whole blood samples from SFTS patients, we found WNT-CTNNB1 signaling pathway was regulated according to the course of the disease. We then demonstrated that L protein of severe fever with thrombocytopenia syndrome virus (SFTSV) could interact with mRNAs of WNT-CTNNB1 signaling pathway-related gene, thus affecting WNT-CTNNB1 signaling pathway through its cap-snatching activity. Activation of WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway decreased SFTSV replication in vitro and in vivo. These findings suggest that WNT-associated genes may be the substrate for SFTSV "cap-snatching", and indicate a conserved sNSVs replication mechanism involving WNT-CTNNB1 signaling.


Loss of Ypk1, the yeast homolog to the human serum- and glucocorticoid-induced protein kinase, accelerates phospholipase B1-mediated phosphatidylcholine deacylation.
Ypk1, the yeast homolog of the human serum- and glucocorticoid-induced kinase (Sgk1), affects diverse cellular activities, including sphingolipid homeostasis. We now report that Ypk1 also impacts the turnover of the major phospholipid, phosphatidylcholine (PC). Pulse-chase radiolabeling reveals that a ypk1Δ mutant exhibits increased PC deacylation and glycerophosphocholine production compared with wild type yeast. Deletion of PLB1, a gene encoding a B-type phospholipase that hydrolyzes PC, in a ypk1Δ mutant curtails the increased PC deacylation. In contrast to previous data, we find that Plb1 resides in the ER and in the medium. Consistent with a link between Ypk1 and Plb1, the levels of both Plb1 protein and PLB1 message are elevated in a ypk1Δ strain compared with wild type yeast. Furthermore, deletion of PLB1 in a ypk1Δ mutant exacerbates phenotypes associated with loss of YPK1, including slowed growth and sensitivity to cell wall perturbation, suggesting that increased Plb1 activity buffers against the loss of Ypk1. Because Plb1 lacks a consensus phosphorylation site for Ypk1, we probed other processes under the control of Ypk1 that might be linked to PC turnover. Inhibition of sphingolipid biosynthesis by the drug myriocin or through utilization of a lcb1-100 mutant results in increased PLB1 expression. Furthermore, we discovered that the increase in PLB1 expression observed upon inhibition of sphingolipid synthesis or loss of Ypk1 is under the control of the Crz1 transcription factor. Taken together, these results suggest a functional interaction between Ypk1 and Plb1 in which altered sphingolipid metabolism up-regulates PLB1 expression via Crz1.


Point-of-care testing in Paediatric settings in the UK and Ireland: a cross-sectional study.
Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT.


Diagnosis and treatment of right ventricular metastasis from esophageal squamous cell carcinoma: An unusual case report and a literature review.
Right ventricular metastasis from esophageal squamous cell carcinoma is very rare and only seen in few case reports. Patients with cardiac metastasis have a poor prognosis with a median survival period of 4 weeks due to the lack of standardized and effective treatment guidelines. Therefore, we aimed to clarify the feature and treatment of cardiac metastasis through literature review and reporting of an unusual case. We reported a case of a 67 years-old man diagnosed as right ventricular metastasis from esophageal squamous cell with the help of echocardiography and pathological biopsy. Moreover, the patient survival period reached an astonishing 6 months, which far exceeded 4 weeks reported in previous literature. We searched for relevant literature in the past decade on PUBMED and summarized the content of the literature to better clarify cardiac metastasis. Cardiac metastatic likely to occur in the elderly and in the right side of heart which related to hemodynamics. Surgical resection of metastatic tumors is the main treatment method, but patients usually die during the perioperative period due to its complexity and difficulty. Meanwhile, we have proposed some potentially effective treatment measures.


Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae: involvement of two hexose transporters.
In the yeast Saccharomyces cerevisiae, multidrug resistance to unrelated chemicals can result from overexpression of ATP-binding cassette (ABC) transporters such as Pdr5p, Snq2p, and Yor1p. Expression of these genes is under the control of two homologous zinc finger-containing transcription regulators, Pdr1p and Pdr3p. Here, we describe the isolation, by an in vivo screen, of two new Pdr1p-Pdr3p target genes: HXT11 and HXT9. HXT11 and HXT9, encoding nearly identical proteins, have a high degree of identity to monosaccharide transporters of the major facilitator superfamily (MFS). In this study, we show that the HXT11 product, which allows glucose uptake in a glucose permease mutant (rag1) strain of Kluyveromyces lactis, is also involved in the pleiotropic drug resistance process. Loss of HXT11 and/or HXT9 confers cycloheximide, sulfomethuron methyl, and 4-NQO (4-nitroquinoline-N-oxide) resistance. Conversely, HXT11 overexpression increases sensitivity to these drugs in the wild-type strain, an effect which is more pronounced in a strain having both PDR1 and PDR3 deleted. These data show that the two putative hexose transporters Hxt11p and Hxt9p are transcriptionally regulated by the transcription factors Pdr1p and Pdr3p, which are known to regulate the production of ABC transporters required for drug resistance in yeast. We thus demonstrate the existence of genetic interactions between genes coding for two classes of transporters (ABC and MFS) to control the multidrug resistance process.


Intractable pain treated with intrathecal isotonic iced saline.
Hitchcock's original method of hypothermic subarachnoid irrigation employed both temperature and osmolarity. Spinal cooling was then abandoned in favour of intrathecal injection of normothermic hypertonic salilne. Modifications of the procedure that followed have continued to accept hyperosmolarity as the factor causing pain relief. Fifty patients were treated by a technique evolved to enhance the effect of hypothermia while avoiding the complications associated with hyperosmolar solutions. For the cases of terminal carcinoma and others considered to be poor surgical risks, the results have been quite satisfactory. For non-neoplastic painful syndromes, rapid perfusion cooling of the subarachnoid space offers an alternative therapeutic approach.


On-site drugs of abuse urinary screening tests for the management of opiate-addicted patients: a survey among French general practitioners.
In France, opiate-addicted patients are mainly managed by general practitioners (GPs). Because on-site abuse drugs urinary screening tests (ODUTs) are now on the market, we investigated French GPs' knowledge and practices concerning drug tests with a focus on ODUTs. We conducted a descriptive cross-sectional study in ambulatory practice. Postal questionnaires were sent to a random sample of GPs in the Midi-Pyrénées area of France in December 2009. Of the 482 GPs in the sample, 116 (24.1%) regularly treated opiate- addicted patients. Only 31 of them (26.7%) used drug tests and 4 of them (3.4%) performed ODUTs in their consultation rooms. Most of the GPs did not perform ODUTs because they were unaware of whether such tests were reliable or available. Many French GPs treating opiate-addicted patients regularly did not perform ODUTs and lacked knowledge of them.


A rare case of aortic valve myxoma: an unusual cause of embolic stroke.
Aortic valve myxoma is an extremely rare cardiac tumour. We describe a 60-year-old woman found to have an aortic valve myxoma and a patent foramen ovale (PFO) presenting as a stroke. In view of the recurrent cerebral ischaemic events, the aortic valve myxoma was surgically removed and the PFO was closed. To the best of our knowledge, this is the first reported case of aortic valve myxoma with a PFO. We also highlight the importance of identifying a possible cardiac source of embolism in a stroke patient and considering this rare tumour as a cause in patients with a cryptogenic stroke.


Microbial Interactions in Oral Communities Mediate Emergent Biofilm Properties.
Oral microbial communities are extraordinarily complex in taxonomic composition and comprise interdependent biological systems. The bacteria, archaea, fungi, and viruses that thrive within these communities engage in extensive cell-cell interactions, which are both beneficial and antagonistic. Direct physical interactions among individual cells mediate large-scale architectural biofilm arrangements and provide spatial proximity for chemical communication and metabolic cooperation. In this review, we summarize recent work in identifying specific molecular components that mediate cell-cell interactions and describe metabolic interactions, such as cross-feeding and exchange of electron acceptors and small molecules, that modify the growth and virulence of individual species. We argue, however, that although pairwise interaction models have provided useful information, complex community-like systems are needed to study the properties of oral communities. The networks of multiple synergistic and antagonistic interactions within oral biofilms give rise to the emergent properties of persistence, stability, and long-range spatial structure, with these properties mediating the dysbiotic transitions from health to oral diseases. A better understanding of the fundamental properties of interspecies networks will lead to the development of effective strategies to manipulate oral communities.


Review-Chemical and Biological Sensors for Viral Detection.
Infectious diseases commonly occur in contaminated water, food, and bodily fluids and spread rapidly, resulting in death of humans and animals worldwide. Among infectious agents, viruses pose a serious threat to public health and global economy because they are often difficult to detect and their infections are hard to treat. Since it is crucial to develop rapid, accurate, cost-effective, and in-situ methods for early detection viruses, a variety of sensors have been reported so far. This review provides an overview of the recent developments in electrochemical sensors and biosensors for detecting viruses and use of these sensors on environmental, clinical and food monitoring. Electrochemical biosensors for determining viruses are divided into four main groups including nucleic acid-based, antibody-based, aptamer-based and antigen-based electrochemical biosensors. Finally, the drawbacks and advantages of each type of sensors are identified and discussed.


Using nursing theory to introduce change in practice.
This article outlines the theoretical basis of nursing using Carper's (1978) fundamental patterns of knowing and explains how this theory can be integrated with practice. The authors also describe how Carper's theory was used to introduce change related to the reduction in junior doctors' hours through the development, implementation and evaluation of nurse practitioners. Using a SWOT analysis exercise and various workshops, practitioners have been able to develop professionally and integrate the art and science of nursing.