Impacts of model resolution and ocean coupling on mean and eddy momentum transfer during the rapid intensification of super-typhoon Muifa (2011).
This study uses a coupled atmosphere-ocean model with different numerical settings to investigate the mean and eddy momentum transfer processes responsible for Typhoon Muifa's (2011) early rapid intensification (RI). Three experiments are conducted. Two use the coupled model with a horizontal resolution of either 1 km (HRL) or 3 km (LRL). The third (NoTCFB) is the same as LRL but excludes tropical cyclone (TC)-induced sea-surface temperature (SST) cooling. HRL reasonably reproduces Muifa's intensity during its rapid intensification and weakening periods. The azimuthal mean tangential and radial momentum budgets are analysed before the RI rates diverge between HRL and LRL. Results show that the dominant processes responsible for Muifa's intensification are different in HRL and LRL. For HRL, the net eddy effect intensifies the storm's circulation and contracts the eyewall during early RI, and it dominates the net mean-flow effect inside the radius of maximum wind (RMW), except near the surface and between 2 and 5 km close to the RMW. In contrast, the mean and eddy effects in LRL almost cancel inside the RMW, while the mean-flow effects dominate and intensify tangential winds outside. Without TC-induced SST cooling, Muifa in NoTCFB reaches a similar storm intensity as in HRL but its rapid weakening rate is substantially underestimated. The dominant mechanisms for tangential wind intensification in NoTCFB are similar to those in LRL, but their magnitudes are larger, implying a misrepresentation of the dominant momentum transfer processes in NoTCFB during RI. For the radial momentum budget analysis, the dominant processes are similar among the three experiments except for some differences in their locations and strengths.


Detection of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp. in clinical specimens using a single-tube multiplex real-time PCR assay.
A multiplex real-time PCR assay for the detection of Mycoplasma pneumoniae (MP181), Chlamydia (Chlamydophila) pneumoniae (CP-Arg), Legionella spp. (Pan-Leg), and the human RNase P (RNase P) gene was developed for rapid testing of atypical bacterial respiratory pathogens in clinical specimens. This method uses 4 distinct hydrolysis probes to detect 3 leading causes of community-acquired pneumonia. The assay was evaluated for specificity and sensitivity by testing against 35 related organisms, a dilution series of each specific target and 197 clinical specimens. Specificity testing demonstrated no cross-reactivity. A comparison to previously validated singleplex real-time PCR assays for each agent was also performed. The analytical sensitivity for specific pathogen targets in both the singleplex and multiplex was identical (50 fg), while efficiencies ranged from 82% to 97% for the singleplex assays and from 90% to 100% for the multiplex assay. The clinical sensitivity of the multiplex assay was improved for the Pan-Leg and CP-Arg targets when compared to the singleplex. The MP181 assay displayed equivalent performance. This multiplex assay provides an overall improvement in the diagnostic capability for these agents by demonstrating a sensitive, high-throughput and rapid method. This procedure may allow for a practical and efficient means to test respiratory clinical specimens for atypical pneumonia agents in health care settings and facilitate an appropriate public health response to outbreaks.


Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients.
Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life. Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4+/-17.2 to 50.4+/-14 mm Hg, P<0.001), RVOT gradient (33+/-24.6 to 19.5+/-15.3, P<0.001), and pulmonary regurgitation (PR) (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21+/-13% versus 3+/-4%, P<0.001) and in RV end-diastolic volume (EDV) (94+/-28 versus 82+/-24 mL.beat(-1).m(-2), P<0.001) and a significant increase in left ventricular EDV (64+/-12 versus 71+/-13 mL.beat(-1).m(-2), P=0.005) and effective RV stroke volume (37+/-7 versus 42+/-9 mL.beat(-1).m(-2), P=0.006) in 28 patients (age 19+/-8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in VO2max (26+/-7 versus 29+/-6 mL.kg(-1).min(-1), P<0.001). There was no mortality. PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.


Demographics, patterns of care, and survival in pediatric medulloblastoma.
We evaluated the American College of Surgeon's National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998-2011 data on medulloblastoma for children ages 0-19 years using logistic and poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0-19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four and younger. Variables associated with receipt of neither radiation nor chemotherapy included age at diagnosis of <1 year, female gender, being of race other than black or white, having no insurance, and living in a residential area with a low level of high school graduates. Better overall survival was observed as age at diagnosis increased, in females, and having received radiation. Compared to medulloblastoma, NOS, better survival was observed for those with demoplastic medulloblastoma, with worse survival in those with large cell medulloblastoma. Majority received multi- disciplinary therapy and radiation had the greatest effect on survival. Ages four and under were most likely to receive chemotherapy and least likely to receive radiation. Suboptimal treatment included 17.8% that did not receive chemotherapy, of which 11.8% received neither chemotherapy nor radiation. Disparities associated with medical access were characteristics for not receiving standard treatment, which resulted in poor outcome.


Potential risk factors for sudden cardiac death: an analysis of medicolegal autopsy cases.
Chronic kidney disease and elevated serum C-reactive protein (CRP) have been suggested as clinical risk factors for cardiac attacks. The present study investigated postmortem blood urea nitrogen (BUN), creatinine (Cr) and CRP levels in the peripheral blood of sudden cardiac death cases. Adult autopsy cases of ischemic heart diseases (n=153, >20 years of age), including acute myocardial infarction (AMI, n=71), recurrent myocardial infarction (RMI, n=47), acute ischemic heart disease without infarction (AIHD, n=27) and chronic ischemic heart disease (CIHD, n=8), were examined and compared with chronic congestive heart disease (CHD, n=24), spontaneous cerebral hemorrhage (SCH, n=17) and mechanical asphyxiation (n=32). BUN was slightly higher for RMI and CHD, although Cr was slightly higher for SCH. CRP was higher for AMI than for AIHD. The correlation between BUN and Cr levels was significant for AMI, AIHD and CHD, but insignificant for RMI and CIHD. Heart weight was larger for all heart diseases and SCH than for asphyxiation, and was larger for RMI and CHD but lower for AIHD and CIHD among them. Body mass index (BMI) was slightly higher for AMI, RMI, AIHD and CHD, remaining within the reference interval in most cases, but was lower for CIHD. These findings suggest different risk factors or etiologies, including active atherosclerosis, latent renal failure, dehydration and cardiac hypertrophy, for sudden deaths due to these heart diseases.


Robot-Assisted Simple Prostatectomy: Expanding on an Established Operative Approach.
The leading cause of voiding dysfunction in older men is benign prostatic obstruction. In the setting of a grossly enlarged prostate (>80cm3), an open simple prostatectomy has been the gold standard for surgical treatment. Here, we will discuss the minimally invasive robot-assisted approach and compare it to the classic open approach and holmium laser enucleation of the prostate. Literature on robot-assisted simple prostatectomy, in concurrence with our institutional experience, has shown an overall lower morbidity, shorter hospital stay, and decreased indwelling catheter time, with equivalent functional outcomes compared to open simple prostatectomy. Similar operative times and hospital stays were found compared to holmium laser enucleation of the prostate, although a steep learning curve and cost of new equipment hinder the wide spread use of this transurethral approach. On review of current literature in addition to our institutional experience, we favor robot-assisted simple prostatectomy over open simple, based on associated increased morbidity/catheter time/hospital stay, and holium laser enucleation of the prostate, based on steep learning curve and cost of new equipment.


Glucose partition coefficient and diffusivity in the lower skin layers.
This work aims to estimate the diffusivity and partitioning of glucose in the dermis and the viable epidermis of human skin. The partition coefficient of glucose between phosphate-buffered saline and dermis, tape-stripped epidermis (TSE), stratum corneum (SC), and split-thickness skin, was measured in vitro using human cadaver skin. Glucose permeability across dermis and tape-stripped split-thickness skin (TSS) was measured using side-by-side diffusion cells. Glucose desorption from TSE and human epidermal membrane (HEM) was measured. All measurements were conducted at 32 degrees C. The partition coefficient for glucose [mean +/- SD (no. of samples)] was 0.65 +/- 0.09 (n = 25) for dermis, 0.81 +/- 0.06 (n = 10) for TSE, and 0.53 +/- 0.12 (n = 9) for SC. Glucose diffusivity in dermis was calculated to be 2.64 +/- 0.42 x 10(-6) cm2/s (n = 14). Glucose diffusivities in the viable epidermis estimated from TSS permeation, TSE desorption, and HEM desorption were 0.075 +/- 0.050 x 10(-6) cm2/s (n = 5), 0.037 +/- 0.018 x 10(-6) cm2/s (n = 4), and 1.0 +/- 0.6 x 10(-6) cm2/s (n = 4), respectively. The tissue/buffer partition coefficient of glucose in all skin layers was found to be less than unity, suggestive of excluded volumes in each layer. Glucose diffusivity in human dermis was found to be one third of its value in water, indicative of hindered diffusion related to the structural components of the tissue. A substantially lower value for glucose diffusivity in viable epidermis is suggested.


Differential Impact of Sleep Deprivation and Circadian Timing on Reflexive Versus Inhibitory Control of Attention.
In a visually stimulating environment with competing stimuli, we continually choose where to allocate attention, and what to ignore. Wake and circadian-dependent modulation of attentional control and resolution of conflict is poorly understood. Twenty-two participants (17males; 25.6 ± 5.6 years) completed ocular motor tasks throughout 40 hours of sleep deprivation under constant routine conditions. A prosaccade task required a reflexive saccade toward a stimulus (no conflict), while an antisaccade task required inhibiting a reflexive saccade to the peripheral stimulus, and looking in the mirror opposite instead (conflict resolution). Antisaccade inhibitory errors showed circadian modulation, being highest in the morning, progressively decreasing until melatonin onset, before returning to the prior morning's peak throughout the biological night. This diurnal rhythm was blunted by sleep loss (>24 hours), with inhibitory control remaining impaired across the second biological day. For prosaccade, responses slowed down during the biological night. Taken together, we provide evidence for a circadian modulation of attentional bias: the morning being biased toward reflexive responding, and the evening toward higher inhibitory control. Our data show that sleep loss and circadian timing differentially impact attention, depending on whether a response conflict is present (antisaccade) or absent (prosaccade).


Retrospective evaluation of appropriate dosing of cefmetazole for invasive urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli.
The frequency of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales is steadily increasing worldwide. Therefore, we aimed to evaluate the efficacy and appropriate dosing of cefmetazole (CMZ) in invasive urinary tract infection (iUTI) caused by ESBL-producing Escherichia coli (ESBLEC). Patients who developed ESBLEC iUTI and received CMZ between January 2007 and December 2018 were identified, and their medical records were reviewed. The time above minimum inhibitory concentration (MIC) (TAM) was calculated using the MIC value obtained from each patient and its simulated CMZ concentration. Thirty-nine patients were included in the study. The median TAM was 92.6% (interquartile range [IQR], 67.6-100). CMZ was clinically efficacious in 38 (97.4%) patients overall and in 11 out of 12 (91.7%) patients with normal renal function who received CMZ at 1 g every 8 h. In normal renal function, 1 g CMZ infused for over 1 h every 8 h is an efficacious treatment for iUTI caused by ESBLEC with MIC =< 4 mg/L.


Safety profile of darolutamide versus placebo: a systematic review and meta-analysis.
Darolutamide is an androgen receptor pathway inhibitor (ARPI) used in patients with prostate cancer (PC). In pivotal trials, it has demonstrated a favorable toxicity profile. There are no head-to-head comparison studies between the different ARPIs, but the efficacy of these drugs seems to be similar making the toxicity profile a key element for treatment selection. We conducted a systematic review of all clinical trials assessing treatment with darolutamide for patients with PC using placebo as the control using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the safety of darolutamide versus placebo evaluating adverse events (AE) leading to treatment discontinuation and the rate of the AE reported as "AE of interest" in the ARAMIS trial. The comparison among darolutamide and the placebo group in terms of safety and tolerability was performed using odds ratio (OR) as meta-analytic outcome. We identified three articles comprising 2902 patients for the systematic review and meta-analysis (1652 treated with darolutamide and 1250 with placebo). Darolutamide did not increase AE leading to treatment discontinuation compared to placebo (pooled OR: 1.176, 95% CI 0.918-1.507, p = 0.633). Regarding the "AE of interest" there was no difference between darolutamide and placebo in terms of asthenia, cardiac arrhythmia, cardiac disorder, coronary artery disorder, depression mood disorder, falls, fatigue, heart failure, hot flushes, hypertension, mental-impairment disorder, rash, seizure and weight loss. The only "AE of interest" with a statistically significant difference in favor of placebo was bone fractures (pooled OR: 1.523, 95% CI 1.081-2.146). In our systematic review and meta-analysis, darolutamide showed a toxicity profile comparable to placebo with the exception of bone fractures. In the absence of head-to-head comparison studies between the different ARPIs, the results of our research suggest a preferred use of darolutamide in the approved settings.


The response of 8th nerve fibers to horizontal sinusoidal oscillation in the alert monkey.
1. The activity of single units in the vestibular nerve was recorded in alert monkeys in stationary positions and during horizontal sinusoidal angular rotations at frequencies from 0.10 to 4.0 Hz. 2. All units encountered had a spontaneous discharge rate which varied from 48.61 to 178.25 spikes/sec. The regularity of firing for each unit also varied. 3. To ipsilateral rotation of the animal the units responded with an increase in firing rate. Rotations in the opposite direction decreased the firing rate relative to the spontaneous discharge rate. The unit response was indicative of imposed velocity rather than acceleration or position. The harmonic distortion of the unit response was not a function of frequency of oscillation. For 43 units at 0.78 Hz the harmonic distortion averaged 23.9%. 4. There was some correlation between the regularity of spontaneous discharge of each unit and the degree of diminished phase lag at higher frequencies of oscillation. Those units with the most irregular spontaneous discharge patterns were most likely to exhibit a diminishing phase lag re:acceleration as frequency of oscillation increased beyond 0.5 Hz. 5. No unit activity related to eye movements was encountered in the vestibular nerve.


Family members of deceased palliative care patients receiving bereavement anniversary cards: a survey on the recipient's reactions and opinions.
Bereavement support is part of palliative care. Sending out bereavement anniversary cards is one intervention of follow-up support for the bereaved. This study evaluated the suitability of bereavement anniversary cards as an appropriate method in bereavement care. A questionnaire was sent to each card recipient since the starting point of this practice (October 2014-June 2015). Data was analyzed descriptively. 24 of 68 deliverable questionnaires were returned (response rate 35%). 22 out of 24 recipients felt pleased receiving the card. No participant felt annoyed on receiving the bereavement anniversary card; every participant agreed to at least one positive reaction (i.e. pleased, grateful or consoled). The participants' reactions and opinions about receiving the anniversary card were decidedly positive and indicate the continuation of this practice. Those few less pleased reactions may be related to timing and the first anniversary of the patients' death and therefore an expression of grief rather than a dissatisfaction with bereavement anniversary cards, as such.


Application of Raman Spectroscopy for the Evaluation of Metabolomic Dynamic Analysis in Athletic Horses.
Raman spectroscopy is a rapid qualitative and quantitative technique that allows the simultaneous determination of several components, both biomolecules both chemical compounds, in the biological fluids to assess the metabolic status. In this study, the serum composition was evaluated in regularly trained athletic horses using Raman spectroscopy to identify biomarkers of sports performance. Five clinically healthy and regularly trained Italian Saddle horses were subjected to a standardized obstacle course (350 m/minute; eleven 1.25 high jumps) preceded by a warm-up. On the collected sera, at rest, immediately after exercise, 30 minutes, and 1 hour after the end of the exercise Raman measurements were performed using a diode laser with the excitation wavelength of 785 nm. The analysis of the obtained spectra allowed the identification of peaks and bands different in position and intensity among the experimental conditions. The acquired spectra, obtained from horse sera collected during the experimental protocol, were visually similar, except for the large band detected in the 1,250-1,800 cm-1 range. The spectral intensity of the Raman spectrum decreased after training and 30 minutes after the end of exercise respect to the before exercise value, to come to the basal value after 60 minutes the end of the exercise. In conclusion, we can claim the ability of Raman spectroscopy to reveal the metabolic status of horses after physical exercise.


Cancer-Associated Fibroblasts in Oral Cancer: A Current Perspective on Function and Potential for Therapeutic Targeting.
The role of the tumour microenvironement (TME) in cancer progression and resistance to therapies is now widely recognized. The most prominent non-immune cell type in the microenvironment of oral cancer (OSCC) is cancer-associated fibroblasts (CAF). Although CAF are a poorly characterised and heterogenous cell population, those with an "activated" myofibroblastic phenotype have been shown to support OSCC progression, promoting growth, invasion and numerous other "hallmarks of malignancy." CAF also confer broad resistance to different types of therapy, including chemo/radiotherapy and EGFR inhibitors; consistent with this, CAF-rich OSCC are associated with poor prognosis. In recent years, much CAF research has focused on their immunological role in the tumour microenvironment, showing that CAF shield tumours from immune attack through multiple mechanisms, and particularly on their role in promoting resistance to anti-PD-1/PD-L1 checkpoint inhibitors, an exciting development for the treatment of recurrent/metastatic oral cancer, but which fails in most patients. This review summarises our current understanding of CAF subtypes and function in OSCC and discusses the potential for targeting these cells therapeutically.


The use of communal rearing of families and DNA pooling in aquaculture genomic selection schemes.
Traditional family-based aquaculture breeding programs, in which families are kept separately until individual tagging and most traits are measured on the sibs of the candidates, are costly and require a high level of reproductive control. The most widely used alternative is a selection scheme, where families are reared communally and the candidates are selected based on their own individual measurements of the traits under selection. However, in the latter selection schemes, inclusion of new traits depends on the availability of non-invasive techniques to measure the traits on selection candidates. This is a severe limitation of these schemes, especially for disease resistance and fillet quality traits. Here, we present a new selection scheme, which was validated using computer simulations comprising 100 families, among which 1, 10 or 100 were reared communally in groups. Pooling of the DNA from 2000, 20000 or 50000 test individuals with the highest and lowest phenotypes was used to estimate 500, 5000 or 10000 marker effects. One thousand or 2000 out of 20000 candidates were preselected for a growth-like trait. These pre-selected candidates were genotyped, and they were selected on their genome-wide breeding values for a trait that could not be measured on the candidates. A high accuracy of selection, i.e. 0.60-0.88 was obtained with 20000-50000 test individuals but it was reduced when only 2000 test individuals were used. This shows the importance of having large numbers of phenotypic records to accurately estimate marker effects. The accuracy of selection decreased with increasing numbers of families per group. This new selection scheme combines communal rearing of families, pre-selection of candidates, DNA pooling and genomic selection and makes multi-trait selection possible in aquaculture selection schemes without keeping families separately until individual tagging is possible. The new scheme can also be used for other farmed species, for which the cost of genotyping test individuals may be high, e.g. if trait heritability is low.


Do anxiety disorders exist in persons with severe and profound mental retardation?
Sixty-nine individuals with severe and profound mental retardation were selected from 289 clients and studied for possible anxiety disorders. The validity of the DASH-II anxiety subscale was evaluated to determine its value in categorizing individuals with and without anxiety. Our findings were mixed. Only behavioral symptoms associated with anxiety could be reliably assessed in these individuals. Unfortunately; this ruled out many core symptoms of the disorder. Implications of the findings are discussed.


The effect of recombinant stem cell factor on human skin and lung mast cells and basophil leukocytes.
Recombinant human stem cell factor (rhSCF) induced histamine release from human skin and lung mast cells but had no effect on human basophil leukocytes. More importantly, rhSCF enhanced the release of histamine in response to IgE-crosslinking of human mast cells. This potentiation was observed at rhSCF concentrations which induced histamine release, and also at lower concentrations of the ligand which by themselves produced no effect. Very limited potentiation was observed with human basophil leukocytes. The enhancing effect of SCF was unique to IgE-dependent stimulation and when SCF was incubated with the neurotransmitter substance P and the calcium ionophore A23187, no augmentation of histamine release was observed with any of the cell types tested. These findings suggest that endogenous SCF may contribute to the regulation of mast cell function and may hence play a role in diverse allergic and inflammatory reactions.


Leflunomide in systemic onset Juvenile idiopathic arthritis.
Methotrexate, the mainstay of treatment in Juvenile idiopathic arthritis, might not be effective in a few patients of polyarticular and systemic onset juvenile idiopathic arthritis. Use of biologicals like TNF-a blockers, the next line of preferred drugs is constrained by the high cost. We successfully used leflunomide in four patients.


GAVI, the Vaccine Alliance.
This year's Lasker-Bloomberg Public Service Award goes to GAVI, the Vaccine Alliance, for providing sustained access to childhood vaccines around the globe, saving millions of lives, and highlighting the power of immunization to prevent disease.


On-line separation and quantification of virus antigens of different serotypes in multivalent vaccines by capillary zone electrophoresis: A case study for quality control of foot-and-mouth disease virus vaccines.
Accurate quantification of effective antigens of different serotypes is crucial for quality control of multivalent vaccines but challenging. A simple and rapid capillary zone electrophoresis (CZE) method was developed for on-line separation and quantification of foot-and-mouth disease virus (FMDV) antigens in monovalent and bivalent FMDV vaccines. The FMDV peak identity in CZE was demonstrated by the study of FMDV dissociation combined with high performance size exclusion chromatography (HPSEC) analysis. After optimizing CZE conditions including UV detecting wavelength, injection volume, and separation voltage, both serotype A and O FMDV showed good reproducibility (RSD <5%) and linear responses (R2=0.999) between the peak area and FMDV content in the concentration range of 15-400 μg/mL. The two serotypes of FMDV with similar size had different migration time in CZE according to their different zeta potential, which allows them to be separated and quantified, with accuracy of <10% relative error. CZE was then successfully applied for antigen quantification of commercial O monovalent and A/O bivalent FMDV vaccines. Compared with HPSEC, CZE was not only able to quantify each serotype of FMDV, but also free from interference of nucleic acids impurities. In summary, the CZE can be a simple, rapid, and reliable tool for quality control of monovalent and bivalent FMDV vaccines. The CZE method can also be further extended to the quality control of other multivalent virus and virus like particle vaccines.


Genetics of B-cell neoplasia.
Somatic cell hybridization experiments between tumorigenic and nontumorigenic cells indicate that the differentiated state of the cells carrying the activated oncogene is important in the regulation of their expression.


Time-course of recovery of dopamine neuron activity during reinnervation of the denervated striatum by fetal mesencephalic grafts as assessed by in vivo voltammetry.
In vivo voltammetry was used to monitor dopamine (DA) neuron activity during the course of reinnervation of the initially denervated caudate-putamen by grafted mesencephalic neurons. Fetal DA neurons were implanted as a cell suspension into the depth of the caudate-putamen in adult 6-hydroxy-dopamine-lesioned recipient rats. Recordings were performed over a period of 2.5-4 months, starting within a week after transplantation, using chronically implanted surface-treated multifiber carbon electrodes. The voltammetric method used in this study has generated considerable discussion centred on the ability of the multifiber electrodes to measure DA alone in vivo, but the results of previous studies have led to the conclusion that changes in the voltammetric signal most probably reflect dopaminergic terminal activity. It seems therefore possible to follow the time-course of changes in the voltammetric signal amplitude during the process of dopaminergic reinnervation of the host striatum from the grafts. A 6-hydroxydopamine lesion of the mesostriatal dopamine pathway caused a substantial (greater than 80%) reduction of the voltammetric signal within 8-10 days, and the low residual signal remained essentially unchanged for time periods up to at least 5 months in the non-grafted control rats. In 7 of 11 rats with DA-rich grafts there was a recovery of the signal amplitude to levels within, or close to, the range recorded from the striatum of normal intact rats. The increase was observed 6-8 weeks after grafting in the rats which had received the largest transplants, and at about 13-14 weeks after grafting in the rats which had received the smallest ones. The recovery of the signal amplitude, from baseline to maximal response, was quite rapid and typically developed between two or three recording sessions, i.e. over a period of one to two weeks. In contrast to the intact striatum, the recovered signal in the graft-reinnervated striata showed a progressive decline within one hour of sampling time at high sampling frequencies (1 per min to 1 per 3 min). Grafted striata also showed a larger response to systemically administered amphetamine than did intact striata. Since the changes in the voltammetric signal recorded with the multifiber electrode mainly reflect dopaminergic terminal activity, the results provide evidence that the intrastriatal DA-rich grafts are spontaneously active, and that the grafted DA neurons can restore DA neuro-transmission in the reinnervated part of the host caudate-putamen to levels which are within the normal range.(ABSTRACT TRUNCATED AT 400 WORDS)


Excretion of benzo[a]pyrene-Gua adduct in the urine of benzo[a]pyrene-treated rats.
A benzo[a]pyrene(BP)-Gua adduct was extracted in the urine of rats treated with BP. Some (0.15%) of the administered dose of BP was excreted as BP-Gua within 48 h. A double labelling experiment demonstrated that the excreted product contained both a BP and a Gua moiety. Partially hepatectomized rats treated with [14C]Gua during the regenerative phase were injected with [3H]BP and the urine collected and processed by chromatographic procedures. The adduct had similar chromatographic properties to the adduct released from human PLC/5 cells treated with 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and co-chromatographed with 7-BPDE-Gua released from BPDE-adducted DNA under aqueous conditions. Detection and quantitation of BP-Gua offers an alternative, non-invasive method of monitoring individuals exposed to carcinogenic polycyclic aromatic hydrocarbons (PAHs).


Overwhelming pneumonia.
Overwhelming pneumonias remain an important cause of morbidity and mortality. These illnesses may be rapidly fatal; thus, many patients are treated empirically. Although the various etiologic agents cannot be differentiated on the basis of radiographic appearance, epidemiologic information may give a clue to the cause. Community-acquired overwhelming pneumonias are usually due to pyogenic bacteria (especially Streptococcus pneumoniae), mycoplasma, mycobacteria, and fungi. Hospital-acquired pneumonias are usually due to aerobic gram-negative bacilli. If the patient is immunocompromised, Pneumocystis carinii, Candida, and Aspergillus must be considered. Choice of optimal antimicrobial therapy requires that a specific etiology be identified. Gram's stain of sputum is often helpful in the diagnosis of community-acquired pneumonia. Invasive diagnostic techniques such as bronchoscopy and open lung biopsy are often required in nosocomial pneumonias and pneumonias in immunocompromised patients.


Long-term consequences of bile duct injury after cholecystectomy.
Late complications arising after bile duct injury (BDI) include biliary strictures, hepatic atrophy, cholangitis and intra-hepatic lithiasis. Later, fibrosis or even secondary biliary cirrhosis and portal hypertension can develop, enhanced by prolonged biliary obstruction associated with recurrent cholangitis. Secondary biliary cirrhosis resulting in associated hepatic failure or digestive tract bleeding due to portal hypertension is a substantial risk factor for morbidity and mortality after bile duct repair. Parameters that determine the management of late complications of BDI include the type of biliary injury, associated vascular injury, hepatic atrophy, the presence of intra-hepatic strictures or lithiasis, repetitive infectious complications, the quality of underlying parenchyma (fibrosis, secondary biliary cirrhosis) and the presence of portal hypertension. Endoscopic drainage is indicated for patients with uncontrolled acute sepsis, patients at high operative risk, patients with cirrhosis who are not eligible for liver transplantation and patients who have previously undergone several attempts at repair. Roux-en-Y hepaticojejunostomy, whether de novo or as an iterative repair, is the technique of reference for post-cholecystectomy BDI. Hepatic resection is indicated in only rare instances, mainly in case of extended hilar stricture, multiple stone retention in one sector of the liver or in patients for whom the repair is deemed technically difficult. Liver transplantation is indicated only in exceptional circumstances, when secondary biliary cirrhosis is associated with liver failure and portal hypertension.


Exosomes derived from cochlear spiral ganglion progenitor cells prevent cochlea damage from ischemia-reperfusion injury via inhibiting the inflammatory process.
Ischemia-reperfusion injury (I/R)-induced inflammatory process can mediate cochlea damage-related hearing loss; whether cochlear spiral ganglion progenitor cell-derived exosomes (CSGPC-exos) play a protective role by carrying functional microRNAs into recipient cells is unknown. Different doses of CSGPC-exos (0.1 μg/μl, 0.2 μg/μl, 0.5 μg/μl, 1.0 μg/μl) were administrated into the cochleae of the I/R group induced with 30-min occlusion of the bilateral vertebral arteries and sham surgery group. The speech-evoked auditory brainstem response (ABR) test was utilized to estimate the auditory threshold shift. The relative expression of proinflammatory cytokines was detected with RT-PCR and Western blot, while parvalbumin and caspase-3 expression were detected by immunofluorescence staining in the cochleae. The relative expression of microRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) was detected in the cochleae. I/R significantly up-regulated ABR threshold shift and promoted hair cell apoptosis indicated by parvalbumin and caspase-3 staining, while CSGPC-exos (0.5 μg/μl, 1.0 μg/μl) could diminish such damages with downregulated proinflammatory factors (IL-6, IL-1β, TNF-α, and Cox-2) and upregulated anti-inflammatory miRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) expression in the cochleae. CSGPC-exos could protect cochleae damage from I/R, probably via inhibiting the inflammatory process.


Association between maternal triglycerides and disturbed glucose metabolism in pregnancy.
Dyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy. Sixty-seven pregnant women received a detailed metabolic characterization at 12+0-22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0-27+6 weeks of gestation. Elevated triglycerides in early gestation were associated with insulin resistance and β-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03-1.34, p=0.022 for an increase of 10 mg/dl). Hypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and β-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.


Theory and computer programs for calculating solution pH, buffer formula, and buffer capacity for multiple component system at a given ionic strength and temperature.
A theory and computer programs running on Microsoft Excel for Windows for calculation of solution pH, buffer formula, and buffer capacity at a given ionic strength and temperature were developed. The theory does not limit the category of buffer components, the number of buffer components, or the number of ionizations for each buffer component. The usefulness of the programs was examined. The formulas for 7 single component buffer solutions and 2 multiple component buffer solutions composed of citrate, phosphate, Tris, borate, and glycine were calculated. The solution pH values were measured at 25, 40, 55 and 70 degrees C for comparison with the calculated pH values. Of the 108 predictions made, 96 were of pH values with +/- 0.1 pH unit of the measured values, at temperatures ranging from 25 degrees C to 70 degrees C and at ionic strengths ranging from 0.1 M to 0.5 M. These programs will be useful for identifying appropriate buffer solutions at various temperatures and/or ionic strengths.


Inelastic neutron scattering study of low energy excitations in polymer thin films.
We report inelastic neutron scattering measurements on polystyrene thin films in a glassy state in the meV region. We found in elastic scattering that the mean square displacement <u2> decreased with film thickness, and hence the corresponding force constant f increased. In inelastic and quasielastic scattering, we observed the so-called boson peak at around 1.5 meV and the picosecond fast process for the first time in thin films, both of which decreased in intensity with film thickness. These results were discussed in terms of the potential hardening due to the confinement of polymer chains and/or the interfacial dead layer.


Parallel modulation of intracortical excitability of somatosensory and visual cortex by the gonadal hormones estradiol and progesterone.
The levels of the gonadal hormones estradiol and progesterone vary throughout the menstrual cycle thereby affecting cognition, emotion, mood, and social behaviour. However, how these hormones modulate the balance of neural excitation and inhibition, which crucially regulate processing and plasticity, is not fully understood. We here used paired-pulse stimulation to investigate in healthy humans the action of low and high estradiol and progesterone on intracortical inhibition in somatosensory (SI) and visual cortex (V1). We found that paired-pulse suppression in both SI and VI depended on estradiol. During high estradiol levels, paired-pulse suppression was significantly reduced. No comparable effects were found for progesterone, presumably due to a confounding effect of estradiol. Also, no hormone level-depending effects were observed for single-pulse evoked SEPs (somatosensory evoked potentials) and VEPs (visual evoked potentials) indicating a specific hormonal action on intracortical processing. The results demonstrate that estradiol globally modulates the balance of excitation and inhibition of SI and VI cortex.


Comment on Ahmmed (2021): The Search for Evidence-Based Auditory Processing Disorder Diagnostic Criteria.
Ahmmed (2021) presented a study to advance the goal of an evidence-based diagnostic criteria for auditory processing disorder. We offer some cautions about the interpretation of these results, as well as suggestions for future strategies for developing evidence-based criteria for auditory processing disorder.


Patterning of multiple layered projections to the auditory midbrain prior to experience.
The precise arrangement of patterned inputs into discrete functional domains is a common organizational feature of primary sensory structures. While the specific organization of patterned connections has been well documented in the visual and somatosensory systems, comparatively little is known about the arrangement of neighboring afferent patterns in the emerging auditory system. Here we report early projection specificity for multiple converging inputs to the rat central nucleus of the inferior colliculus (ICC). Afferents arising from the dorsal cochlear nucleus (DCN), the dorsal nucleus of the lateral lemniscus (DNLL), and the lateral superior olive (LSO) establish discernible axonal layers a week prior to experience. By hearing onset, contralateral DCN and contralateral LSO layers are clearly defined and segregated from contralateral DNLL terminal zones. Layering of the ipsilateral LSO projection, on the other hand, exhibits considerable spatial overlap with the contralateral DNLL pattern. This fine laminar structure of interdigitating and overlapping inputs likely underlies the complex signal processing performed in the auditory midbrain and may serve as a model system for examining competitive interactions between neighboring excitatory and inhibitory projections early in development.


Inflammatory fibrous histiocytoma presenting as a renal pelvic and bladder mass.
The first case of simultaneous presentation of a bladder and renal pelvic malignant fibrous histiocytoma is reported. Although only a small percentage of fibrous histiocytomas are malignant the lesion is extremely aggressive. Radiotherapy and chemotherapy have been used but only sporadic remissions have been reported. If the tumor is localized wide surgical excision is recommended.


Trapeziectomy and Abductor Pollicis Longus Suspensionplasty Combined with Extensor Pollicis Brevis Tenodesis for Management of Thumb Basal Joint Osteoarthritis and Metacarpophalangeal Hyperextension.
Metacarpal joint hyperextension is common cause of postoperative dissatisfaction after trapeziectomy in the management of basal thumb osteoarthritis. The senior author uses this technique to address this biomechanical problem at the time of trapeziectomy.


DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development.
Drak2-deficient (Drak2-/-) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Here, we demonstrate that resistance to T1D in non-obese diabetic (NOD) mice is due to the absence of Drak2 in T cells and requires the presence of regulatory T cells (Tregs). Contrary to previous hypotheses, we show that DRAK2 does not limit TCR signaling. Rather, DRAK2 regulates IL-2 signaling by inhibiting STAT5A phosphorylation. We further demonstrate that enhanced sensitivity to IL-2 in the absence of Drak2 augments thymic Treg development. Overall, our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic Treg development and by impacting the sensitivity of conventional T cells to Treg-mediated suppression.


Gene expression studies and molecular characterization of a cathepsin L-like from the Asian citrus psyllid Diaphorina citri, vector of Huanglongbing.
Huanglongbing (HLB) is a devastating citrus disease associated with Candidatus Liberibacter asiaticus (CLas) and is transmitted by the psyllid Diaphorina citri Kuwayama. Diaphorina citri belongs to Hemiptera order, which has cysteine peptidases as the most abundant proteolytic enzymes present in digestive tract. As cysteine peptidases are involved in different insect development processes, this class of enzymes has acquired biotechnological importance. In this context, we identified a cathepsin L-like (DCcathL1) from the Diaphorina citri transcriptome database and expressed the enzyme in E. coli. Quantitative real-time RT-PCR was conducted to determine DCcathL1 gene expression in different parts and developmental phases of the insect. We observed that DCcathL1 expression in the gut was 2.59 and 2.87-fold higher than in the head and carcass, respectively. Furthermore, DCcathL1 expression was greater in eggs than in nymphs and adults, suggesting a putative role of the enzyme in the embryonic development. In addition, enzymatic inhibitory activity using four recombinant Citrus cystatins were performed. Among them, CsinCPI-2 was the strongest DCcathL1 inhibitor with a Ki value of 0.005 nM. Our results may contribute in the development of strategies for D. citri control, such as silencing the DCcathL1 gene and the use of transgenic plants that overexpress peptidase inhibitors.


Efficacy of adding high-dose In-111 octreotide therapy during Sandostatin treatment in patients with disseminated neuroendocrine tumors: clinical results of 14 patients.
This study aimed to assess the outcome of high-dose In-111 octreotide treatment and efficacy of long-acting Sandostatin LAR in patients with disseminated neuroendocrine tumors. A total of 14 patients (mean age 51.8 ± 13.2 years; 10 female, 4 male) receiving high-dose In-111 octreotide in our centre for the treatment of neuroendocrine tumors were included in the study. Monthly treatment with long-acting somatostatin analogue [Sandostatin long-acting release (Novartis Pharmaceuticals)] was continued in nine cases. During a 3-year period, a total of 45 courses of high-dose In-111 octreotide treatment were delivered to 14 patients. In seven patients receiving an average of four treatment courses (6 carcinoid tumors, 1 thymoma, patients: 2, 4, 5, 11-14) stable disease was achieved (50%). In two patients with carcinoid tumors (patients 1 and 3) who received four treatment courses, partial response was observed (14%). Five patients (36%; 4 NET, 1 gastrinoma; patients 6-10) died due to progressive disease following on average two treatment courses. On average, deaths occurred 2 months after the last treatment dose. No complete responses were seen. Partial response was achieved in two of the nine patients receiving Sandostatin LAR, while four had stable disease. Both treatments were associated with acceptable tolerability. High-dose In-111 octreotide can be safely administered in conjunction with somatostatin analogue in patients with disseminated NET and this treatment may help to stabilize the disease.


Ambient biomass smoke and cardio-respiratory hospital admissions in Darwin, Australia.
Increasing severe vegetation fires worldwide has been attributed to both global environmental change and land management practices. However there is little evidence concerning the population health effects of outdoor air pollution derived from biomass fires. Frequent seasonal bushfires near Darwin, Australia provide an opportunity to examine this issue. We examined the relationship between atmospheric particle loadings <10 microns in diameter (PM10), and emergency hospital admissions for cardio-respiratory conditions over the three fire seasons of 2000, 2004 and 2005. In addition we examined the differential impacts on Indigenous Australians, a high risk population subgroup. We conducted a case-crossover analysis of emergency hospital admissions with principal ICD10 diagnosis codes J00-J99 and I00-I99. Conditional logistic regression models were used to calculate odds ratios for admission with 10 microg/m3 rises in PM10. These were adjusted for weekly influenza rates, same day mean temperature and humidity, the mean temperature and humidity of the previous three days, days with rainfall > 5 mm, public holidays and holiday periods. PM10 ranged from 6.4 - 70.0 microg/m3 (mean 19.1). 2466 admissions were examined of which 23% were for Indigenous people. There was a positive relationship between PM10 and admissions for all respiratory conditions (OR 1.08 95%CI 0.98-1.18) with a larger magnitude in the Indigenous subpopulation (OR1.17 95% CI 0.98-1.40). While there was no relationship between PM10 and cardiovascular admissions overall, there was a positive association with ischaemic heart disease in Indigenous people, greatest at a lag of 3 days (OR 1.71 95%CI 1.14-2.55). PM10 derived from vegetation fires was predominantly associated with respiratory rather than cardiovascular admissions. This outcome is consistent with the few available studies of ambient biomass smoke pollution. Indigenous people appear to be at higher risk of cardio-respiratory hospital admissions associated with exposure to PM10.


NetAP-ML: Machine Learning-Assisted Adaptive Polling Technique for Virtualized IoT Devices.
To maximize the performance of IoT devices in edge computing, an adaptive polling technique that efficiently and accurately searches for the workload-optimized polling interval is required. In this paper, we propose NetAP-ML, which utilizes a machine learning technique to shrink the search space for finding an optimal polling interval. NetAP-ML is able to minimize the performance degradation in the search process and find a more accurate polling interval with the random forest regression algorithm. We implement and evaluate NetAP-ML in a Linux system. Our experimental setup consists of a various number of virtual machines (2-4) and threads (1-5). We demonstrate that NetAP-ML provides up to 23% higher bandwidth than the state-of-the-art technique.


Analysis using image segmentation for the elemental composition of activated carbon.
This article encompasses the method related to image segmentation of the Field Emission Scanning Electron Microscope (FESEM) images of Acacia Mangium Wood derived Activated Carbons under different conditions. Image segmentation using Hue-Saturation-Value (HSV) thresholding method was adapted to identify the different pattern composition in the grayscale images by varying the intensity Value (V) and keeping Hue (H) and Saturation (S) to zero, and each pattern was considered as one type of element that constituted the Activated Carbon. The algorithm was developed to compute the percentage of each pattern using non-zero pixels, and on the basis of different patterns, different elements having certain percentage of composition were recorded. Later, these results were compared with the Energy Dispersive X-ray Spectroscopy (EDS) to cross check the difference in percentage of each element present at the surface of the Activated Carbon. Part of this result is published in the article [1], "Comparison of surface properties of wood biomass Activated Carbons and their application against rhodamine B and methylene blue dye" Surfaces and Interfaces vol. 11 (2018) pp1-13.•The methods involved will be useful for characterization of Activated Carbon materials.•Image segmentation using HSV thresholding will inspire other researchers to apply similar concept on other materials.•Different patterns obtained for FESEM images using HSV thresholding was able to determine the presence of multiple elements present in the prepared Activated Carbon samples.


Prevention of disability and rehabilitation--results from a collaborative project in China.
Eight different geographical districts in China varying in urban and rural characteristics from 6 provinces and 2 municipalities were selected as pilot areas of the project. The interventions included early detection and treatment of neuritis, self-care training, adapted footwear, surgery, comprehensive treatment of complicated ulcers, and prostheses. Main changes in eye, hand and foot impairments between baseline assessment and assessment at 2 years have been presented in this paper.


Gentamicin-Loaded Thermosetting Hydrogel and Moldable Composite Scaffold: Formulation Study and Biologic Evaluation.
The aim was to design biodegradable drug delivery systems for gentamicin local delivery, meanwhile acting as scaffold for bone regeneration. Gentamicin-loaded thermosetting composite hydrogels were prepared combining chitosan with bovine bone substitutes (Orthoss® granules), beta-glycerophosphate as cross-linker, and lyophilized to obtain moldable composite scaffolds (moldable composite scaffold loaded with gentamicin [mCSG]). Diverse techniques for gentamicin loading into mCS were investigated by drug incorporation during hydrogel preparation or drug absorption on preformed mCS. Rheologic hydrogel characterization was performed. mCSGs were characterized for porosity, stability (water retention, water uptake), gentamicin release, cell seeding and proliferation, and antimicrobial effect on Escherichia coli ATCC 10356. Results show suitable gentamicin loadings were 4 mg in 1 mL thermosetting composite hydrogel starting solution, irreversible hydrogel thermosetting behavior, and cosolute effect of gentamicin on sol-gel transition. Positive results in terms of porosity (80%-86%), scaffold water uptake, and retention capability were obtained. Antibiotic in vitro release was completed in 4 h. Good cell seeding results were observed for mCSG1-5; mCSG3 and mCSG5 resulted the best as cell proliferation results. mCSG exerted bactericidal effect for 24 h, with superimposition of chitosan bacteriostatic effect in the first 4 h. The results lead to consider the drug delivery for reducing infection risk during bone open surgeries.


Massive left atrial calcification.
We reported this case because calcification of the mitral valve is a common complication of rheumatic fever, but calcification of the left atrium is rare.


Evaluating sediment and water sampling methods for the estimation of deep-sea biodiversity using environmental DNA.
Despite representing one of the largest biomes on earth, biodiversity of the deep seafloor is still poorly known. Environmental DNA metabarcoding offers prospects for fast inventories and surveys, yet requires standardized sampling approaches and careful choice of environmental substrate. Here, we aimed to optimize the genetic assessment of prokaryote (16S), protistan (18S V4), and metazoan (18S V1-V2, COI) communities, by evaluating sampling strategies for sediment and aboveground water, deployed simultaneously at one deep-sea site. For sediment, while size-class sorting through sieving had no significant effect on total detected alpha diversity and resolved similar taxonomic compositions at the phylum level for all markers studied, it effectively increased the detection of meiofauna phyla. For water, large volumes obtained from an in situ pump (~ 6000 L) detected significantly more metazoan diversity than 7.5 L collected in sampling boxes. However, the pump being limited by larger mesh sizes (> 20 µm), only captured a fraction of microbial diversity, while sampling boxes allowed access to the pico- and nanoplankton. More importantly, communities characterized by aboveground water samples significantly differed from those characterized by sediment, whatever volume used, and both sample types only shared between 3 and 8% of molecular units. Together, these results underline that sediment sieving may be recommended when targeting metazoans, and aboveground water does not represent an alternative to sediment sampling for inventories of benthic diversity.


The impact of plasma folate levels of mothers and newborns on intrauterine growth retardation and birth weight.
Folate plays an important role in the genomic stability of human cells. In our studies of the impact of environmental pollution on human health, we have found that air pollution can affect pregnancy outcome. As it may be also affected by nutrition, we examined the effect of plasma folate levels of mothers and newborns on intrauterine growth retardation (IUGR) and birth weight (BW) in cohorts from Prague (N=319) and Teplice (N=444). The lower plasma levels (<6.1 nmol/L) were observed in 7.1% of mothers in Prague, and in 9.6% of mothers in Teplice. The higher plasma levels (>36.5 nmol/L) were observed in 28.4% of mothers in Prague, and in 15.7% of mothers in Teplice. The higher plasma levels were observed in 75.4% of newborns in Prague, and 73.2% of newborns in Teplice. When comparing maternal high versus low folate plasma levels and IUGR by logistic regression, the risk of IUGR was significantly decreased for European cohort (according to ethnicity) with gestation age >36 weeks [N=536, OR=0.44, P=0.026], and even more pronounced in the group of European smokers [N=157, OR=0.14, P=0.015]. Using multiple regression analysis, plasma folate levels of mothers and newborns significantly affected the birth weight of newborns of smoking mothers (P<0.05). The obtained results seem to indicate a positive effect of folate on pregnancy outcome, especially its potential to decrease the risk of IUGR in European population and lower birth weight in smoking European mothers. It would be warranted to study the effect of folate levels on pregnancy outcomes in the relationship to different environmental pollution and life styles of mothers.


Libyan cancer patients at King Hussein Cancer Center for more than a decade, the current situation, and a future vision.
Since 2011, the Libyan civil war crisis had affected all dimensions of livelihood including cancer care. This has resulted in a steady incline in the number of Libyan patients with cancer seeking oncologic care and management in Tunisia, Egypt and Jordan, among others. King Hussein Cancer Center (KHCC) has been one of the main destinations for Libyan patients with cancer for more than a decade. We are reporting on the characteristics of Libyan patients with cancer presenting to KHCC during the past fourteen years. We performed a retrospective chart review of all Libyan patients with cancer presenting to KHCC between 2006 and 2019. A total of 3170 records were included in the final analysis. The overall sample was predominantly adults (71%) with a male-to-female ratio of 1:1.2. Overall, the most common referred cancers to KHCC were breast (21%), hematolymphoid (HL) (17%), and gastrointestinal tract (GIT) (16.2%) cancers. Breast cancer was the most common among adult females (41.7%), GIT among adult males (23.6%), and HL among pediatrics (38.5%). Around 37.8% of patients presented with distant metastasis at their first encounter at KHCC, among which 14.7% were candidates for palliative care. The sustenance of treatment for Libyan patients with cancer requires extensive collaboration between governmental and private sectors. The Libyan oncological landscape could benefit from national screening and awareness programs, twining programs and telemedicine, introduction of multidisciplinary boards, and the formulation of a national cancer registry. Adopting the successful models at KHCC can help to augment the oncology services within the Libyan healthcare sector.


Right ventricular systolic function during exercise with and without significant coronary artery disease.
To evaluate the effects of exercise and coronary artery disease on right ventricular (RV) systolic function, rest and exercise biplane RV angiograms were recorded in 20 patients undergoing diagnostic cardiac catheterization. Thirteen patients had exercise angiograms of sufficient quality to undergo analysis and were classified into 2 groups. Group 1 had no or only mild coronary artery disease; group 2 had significant coronary artery disease as manifested by new, exercise-induced, left ventricular regional wall motion abnormalities. RV systolic pressure increased in both groups during exercise: 33 to 57 mm Hg in group 1 (p = 0.0002) and 33 to 55 mm Hg in group 2 (p = 0.0004). Pulmonary resistance did not change in group 1 during exercise but increased in group 2 (3.2 to 4.8 Wood units, p = 0.04). RV ejection fraction increased slightly, but not significantly, during exercise in group 1, but decreased in group 2 (73 vs 58% with exercise [p = 0.01]). The change in RV ejection fraction from rest to exercise correlated closely with the change in pulmonary resistance from rest to exercise (r = -0.89, p less than 0.0001). RV regional wall motion analysis demonstrated a generalized decline in regional ejection fraction in group 2 during exercise, even in patients without right coronary artery disease. In conclusion, there is a decline in RV ejection fraction during exercise in patients with significant coronary artery disease. The generalized reduction in regional RV ejection fraction coupled with the close correlation with the change in pulmonary resistance suggests that increased afterload, rather than RV ischemia, is the cause.


10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis.
Lactococcus lactis is a Gram-positive lactic acid bacterium that, in addition to its traditional use in food fermentations, is increasingly used in modern biotechnological applications. In the last 25 years great progress has been made in the development of genetic engineering tools and the molecular characterization of this species. A new versatile and tightly controlled gene expression system, based on the auto-regulation mechanism of the bacteriocin nisin, was developed 10 years ago-the NIsin Controlled gene Expression system, called NICE. This system has become one of the most successful and widely used tools for regulated gene expression in Gram-positive bacteria. The review describes, after a brief introduction of the host bacterium L. lactis, the fundaments, components and function of the NICE system. Furthermore, an extensive overview is provided of the different applications in lactococci and other Gram-positive bacteria: (1) over-expression of homologous and heterologous genes for functional studies and to obtain large quantities of specific gene products, (2) metabolic engineering, (3) expression of prokaryotic and eukaryotic membrane proteins, (4) protein secretion and anchoring in the cell envelope, (5) expression of genes with toxic products and analysis of essential genes and (6) large-scale applications. Finally, an overview is given of growth and induction conditions for lab-scale and industrial-scale applications.


Reduced anaphylactic potential of denatured pullulan-conjugated Cry j 1.
Japanese Cedar (JC) pollinosis is the most common seasonal allergic rhinitis in Japan. Throughout the JC pollen season, patients suffer from the allergic symptoms, resulting in a reduction of quality of life. Allergy immunotherapy (AIT) is an established treatment option for a wide range of allergens that unlike symptomatic treatments (e.g. antihistamines) may provide sustained immune tolerance. However, AIT, especially subcutaneous immunotherapy (SCIT) has a fatal anaphylaxis risk due to the use of crude allergen extracts. Consequently, development of allergen derivatives with substantially reduced anaphylactic potential is desirable. An allergen derivative that showed reduced IgE-binding and anaphylactic potential was developed through conjugation of native Cry j 1 (n Cry j 1), a major JC allergen, to the polysaccharide pullulan followed by chemical but non-covalent denaturation. The resulting Cry j 1 allergen derivative, Dn p-Cry j 1, showed reduced IgE-binding and IgE-mediated effector cell activation in vitro using an ELISA competition assay and a mast cell activation model (EXiLE). Reduced anaphylactic potential of Dn p-Cry j 1 in vivo was demonstrated using the rat passive cutaneous anaphylaxis (PCA) assay. The difference in anaphylactic potential of Dn p-Cry j 1 compared to n Cry j 1 in wild-type rats was of the same magnitude as the difference seen in the anaphylaxis reactions obtained with n Cry j 1 in wild-type rats and mast-cell deficient rats, indicating a dramatic reduction in anaphylactic potential of Dn p-Cry j 1. These results indicate that Dn p-Cry j 1 is a promising candidate for next-generation JC AIT.


A Case of Atrophic Dermatofibroma Overexpressing Matrix Metalloproteinase-1.
This case report describes the importance of considering this tumor as one of the differential diagnoses when we encounter a flat and/or atrophic and depressible lesion in the upper portion of the trunk.


Validation and Psychometric Properties of the Spanish Version of the Hopkins Symptom Checklist-25 Scale for Depression Detection in Primary Care.
Depression constitutes a major public health problem due to its high prevalence and difficulty in diagnosis. The Hopkins Symptom Checklist-25 (HSCL-25) scale has been identified as valid, reproducible, effective, and easy to use in primary care (PC). The purpose of the study was to assess the psychometric properties of the HSCL-25 and validate its Spanish version. A multicenter cross-sectional study was carried out at six PC centers in Spain. Validity and reliability were assessed against the structured Composite International Diagnostic Interview (CIDI). Out of the 790 patients, 769 completed the HSCL-25; 738 answered all the items. Global Cronbach's alpha was 0.92 (0.88 as calculated for the depression dimension and 0.83 for the anxiety one). Confirmatory factor analysis (CFA) showed one global factor and two correlated factors with a correlation of 0.84. Area under the curve (AUC) was 0.89 (CI 95%, 0.86-0.93%). For a 1.75 cutoff point, sensibility was 88.1% (CI 95%, 77.1-95.1%) and specificity was 76.7% (CI 95%, 73.3-79.8%). The Spanish version of the HSCL-25 has a high response percentage, validity, and reliability and is well-accepted by PC patients.


Alphas, betas and skewy distributions: two ways of getting the wrong answer.
Although many parametric statistical tests are considered to be robust, as recently shown in Methodologist's Corner, it still pays to be circumspect about the assumptions underlying statistical tests. In this paper I show that robustness mainly refers to α, the type-I error. If the underlying distribution of data is ignored there can be a major penalty in terms of the β, the type-II error, representing a large increase in false negative rate or, equivalently, a severe loss of power of the test.


Effects of pollutants on laccase activities of Marasmius quercophilus, a white-rot fungus isolated from a Mediterranean schlerophyllous litter.
Marasmius quercophilus is a white-rot fungus involved in carbon recycling in Mediterranean ecosystems because of its laccase production. Here we described the effect of metal ions and halide salts, on laccase activity in order to point out the action of such environmental pollutants on this enzyme of major importance. Furthermore we tested organic solvent effects on laccase reaction since reaction mixture including solvent can be used in the transformation of xenobiotics. In the case of metal ions, we found that chloride ions were responsible for inhibition while CuSO(4) and MnSO(4) enhanced laccase activity. When halides were tested, we showed the following degree of inhibition: F(-)>Cl(-)>Br(-). Furthermore we found that I(-) was oxidized by laccase with I(2) as the product of the reaction. With ABTS, 50% of the laccase activity remains for solvent concentration ranging from 40% to 60% depending on the solvent used while with syringaldazine solvent concentration ranged from 50% to 70%. The organic solvent effects observed were probably a result of enzyme denaturation and of both enhancement of oxidised product solubilisation and of substrate solubilisation (for syringaldazine). These results show that laccase from M. quercophilus is not rapidly inhibited by certain environmental pollutants which sustains its role in carbon turnover under pertubation. However the strong effect of chloride ion on laccase activity should be further investigated with in situ studies since this could drastically influence carbon recycling in litters from Mediterranean littoral locations.


Study protocol for a parallel-group randomized controlled multi-center trial evaluating the additional effect of continuous ultrasound bladder monitoring in urotherapy for children with functional daytime urinary incontinence (SENS-U trial).
Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year-old children. It is associated with an impaired quality of life, lower self-esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS-U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS-U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost-effectiveness is to be determined. This is a multi-center clinical superiority parallel-group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS-U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS-U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group. To our knowledge, this is the first trial studying not only the effect but also the cost-effectiveness of alarm interventions as commonly added in urotherapy. ISRCTN44345202 . Registered on March 2022.


Adaptation process of engineered cell line FCHO/IL-24 stably secreted rhIL-24 in serum-free suspension culture.
Interleukin-24 (IL-24) displays tumor cell-specific proliferation inhibition in vitro and in vivo. Recombinant human IL-24 (rhIL-24) has significantly higher activity, yet significantly lower expression level in mammalian cells than in bacteria. To further realize therapeutic potential of IL-24, we enhanced rhIL-24 expression in mammalian cell systems by adapting engineered Flp-InTMCHO/IL-24 (FCHO/IL-24) cells (adherent cultured in Ham's F12 medium with 10% serum) to serum-free suspension culture. First, MTT assay showed that among four different media (F12, DMEM/F12, 1640 and DMEM), DMEM/F12 medium was the most suitable media for lower-serum adherent culture. Then, cells were adherently cultured in DMEM/F12 with serum concentration reduced from 10% to 0.5% in a gradient manner. Compared to cells in 10% serum, cells in 0.5% serum displayed significantly lower relative cell viability by 40%, increased G0/G1 phase arrest (8.5 ± 2.4%, p < 0.05), decreased supernatant rhIL-24 concentration by 73%, and altered metabolite profiles, such as glucose, lactate and ammonia concentration. Next, the cells were directly adapted to 0.5% serum suspension culture in 125 mL shake flask at 119 rpm with the optimal cell seeding density of 5 × 105 cells/mL (3.3 times higher than that of adherent culture), under which the concentration of rhIL-24 in culture medium was stable at 3.5 ng/mL. Finally, cells adapted to 0.5% serum proliferated better in serum-free medium Eden™-B300S with higher rhIL-24 expression level compared to CDM4CHO. The successful adaptation of engineered cells FCHO/IL-24 laid foundation for adapting cells from adherent culture to suspension serum-free culture to mass produce rhIL-24 protein for therapeutic purposes.


Hepatocyte nuclear factor-3beta limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo.
Hepatocyte nuclear factor-3beta (HNF-3beta), a nuclear protein of the winged helix family of transcription factors, is known to play a critical role in the formation of the embryonic node, notochord, and foregut endoderm. HNF-3beta influences the expression of a number of target genes in the respiratory epithelium, activating transcription of thyroid transcription factor-1, surfactant protein-B and clara cell secretory protein. In order to discern the role of HNF-3beta in differentiation and gene expression in the lung, HNF-3beta was expressed in developing respiratory epithelial cells of transgenic mice, under the control of the human surfactant protein C gene promoter. Pulmonary abnormalities were observed in the lungs of fetal mice bearing the HNF-3beta transgene. Differentiation of distal respiratory epithelial cells was arrested in the early pseudoglandular stage. Branching morphogenesis and vasculogenesis were markedly disrupted in association with decreased E-cadherin and vascular endothelial growth factor expression. HNF-3beta limits cellular diversity of developing respiratory epithelium and alters lung morphogenesis in vivo, suggesting that precise temporal-spatial regulation of HNF-3beta expression is critical for respiratory epithelial cell differentiation and lung morphogenesis.


Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric determinants of the SARS-CoV-2 spike protein binding with nanobodies, we also examined nanobody-induced modulation of escaping mutations and the effect of the Omicron variant on nanobody binding. The mutational scanning analysis supported the notion that E484A mutation can have a significant detrimental effect on nanobody binding and result in Omicron-induced escape from nanobody neutralization. Our findings showed that SARS-CoV-2 spike protein might exploit the plasticity of specific allosteric hotspots to generate escape mutants that alter response to binding without compromising activity. The network analysis supported these findings showing that VHH E/VHH V nanobody binding can induce long-range couplings between the cryptic binding epitope and ACE2-binding site through a broader ensemble of communication paths that is less dependent on specific mediating centers and therefore may be less sensitive to mutational perturbations of functional residues. The results suggest that binding affinity and long-range communications of the SARS-CoV-2 complexes with nanobodies can be determined by structurally stable regulatory centers and conformationally adaptable hotspots that are allosterically coupled and collectively control resilience to mutational escape.


Boosting the reaction kinetics in aprotic lithium-carbon dioxide batteries with unconventional phase metal nanomaterials.
Given the high energy density and eco-friendly characteristics, lithium-carbon dioxide (Li-CO2) batteries have been considered to be a next-generation energy technology to promote carbon neutral and space exploration. However, Li-CO2 batteries suffer from sluggish reaction kinetics, causing large overpotential and poor energy efficiency. Here, we observe enhanced reaction kinetics in aprotic Li-CO2 batteries with unconventional phase 4H/face-centered cubic (fcc) iridium (Ir) nanostructures grown on gold template. Significantly, 4H/fcc Ir exhibits superior electrochemical performance over fcc Ir in facilitating the round-trip reaction kinetics of Li+-mediated CO2 reduction and evolution, achieving a low charge plateau below 3.61 V and high energy efficiency of 83.8%. Ex situ/in situ studies and theoretical calculations reveal that the boosted reaction kinetics arises from the highly reversible generation of amorphous/low-crystalline discharge products on 4H/fcc Ir via the Ir-O coupling. The demonstration of flexible Li-CO2 pouch cells with 4H/fcc Ir suggests the feasibility of using unconventional phase nanomaterials in practical scenarios.


Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes.
Ruthenium (Ru) and osmium (Os) complexes are of sustained interest in cancer research and may be alternative to platinum-based therapy. We detail here three new series of ruthenium and osmium complexes, supported by physico-chemical characterizations, including time-dependent density functional theory, a combined experimental and computational study on the aquation reactions and the nature of the metal-arene bond. Cytotoxic profiles were then evaluated on several cancer cell lines although with limited success. Further investigations were, however, performed on the most active series using a genetic approach based on RNA interference and highlighted a potential multi-target mechanism of action through topoisomerase II, mitotic spindle, HDAC and DNMT inhibition.


Factors associated with reported likelihood to get vaccinated for COVID-19 in a nationally representative US survey.
Although general principles related to vaccination hesitancy have been well researched, reports on reluctance to be vaccinated for coronavirus disease 2019 (COVID-19) in the United States are somewhat surprising, given the disease's substantive disruption of everyday life. However, the landscape in which people are making COVID-19 vaccination decisions has recently evolved with releases of encouraging vaccine-related data and changes to official messaging about the virus. Therefore, this study sought to identify factors associated with reported likelihood to get vaccinated for COVID-19 among US adults in late January 2021. We used the Prolific online research panel to survey a nationally representative sample of 1017 US adults. Respondents were asked about their behavioral intentions toward COVID-19 vaccination, trust in science, perceptions related to COVID-19, and selected sociodemographic factors. We computed associations between those 11 independent variables and likelihood to get vaccinated for COVID-19 using multiple linear regression. Around 73.9% of respondents indicated at least some likelihood to get vaccinated for COVID-19. Trust in science and perceived seriousness of COVID-19 were positively associated with intention to get vaccinated, and identifying as Black or African American was negatively associated with intention to get vaccinated. Other factors were moderately, weakly, or not at all associated with intention. Building trust in science and truthfully emphasizing the seriousness of catching COVID-19 should be further researched for their potential to support campaigns to encourage COVID-19 vaccination. Data continue to suggest the importance of dialogue with Black communities about COVID-19 vaccination.


Lower limb dynamics change for children while walking with backpack loads to modulate shock transmission to the head.
Backpack load carriage increases ground reaction forces and increases the stiffness in the upper extremity that can cause transmission of higher amount of forces from the lower extremity to the head. This study investigated the effect of load carriage and placement of load on the back on the shock transmission mechanisms amongst children. Fifteen primary school boys with mean age 10.01 (+/-1.31) years, mean height 136.40 (+/-10.08)cm and mean mass 31.83 (+/-7.13)kg completed the study. Subjects carried 10%, 15% and 20% bodyweight (BW) loads on two locations on the back, namely upper and lower. Results showed a significant reduction in pelvic and trunk rotation in the transverse plane and an increase in the upper body stiffness for loads exceeding 15% of BW. The lower limb results showed a reduction in the first peak force and cadence and a significant change in the walking velocity and time to the first peak force for 20% load. No significant differences were found for the load configuration but the upper configuration showed slightly higher shock transmission. The changes in the lower limb dynamics indicated that there are locomotion mechanisms in place amongst children to modulate shock transmission to the head.


Should we root treat children's first permanent molars?
Study selection Medline via PubMed and Embase were searched on 6 November 2019 and all studies up to this date were included, including case reports and case series. This was noted as being due to the limited number of studies available in this research area. The outcome measured was clinical success, which was defined as the tooth being present and an assumption that it was sound and asymptomatic at the end of the study. Studies that did not include a minimum of six months' follow-up were excluded, as were editorial letters, in vitro studies and studies not reported in English.Data extraction and synthesis One reviewer searched databases for appropriate studies, then a second reviewer assisted in assessing studies by title and abstract. For each eligible article the operator, sample size, and a full dental diagnosis were recorded. Treatment method, follow-up and treatment success were also assessed.Results The systematic review included eleven studies. The GRADE approach was used to assess quality of evidence. Three studies were of high quality, six of low quality, and two of very low quality. Cochrane and Robins-I risk tools were used to assess bias. All randomised controlled trials were assessed to be of high risk of bias, due to the blinding process not being stated. Six non-randomised controlled trials were assessed to be of critical risk of bias, as the measurement of treatment outcomes was not stated. There was a high risk of bias determined overall.The review reported a 90.5% (range 70-100%) success rate over a mean follow-up period of 28.4 months (range 6-73.6 months) for coronal pulpotomies, which is in line with the results from adult studies. For partial pulpotomies the review reported a 91.3% (range 78.5-100%) success rate over a mean follow-up period of 34.4 months (range 12-140 months), which is slightly lower than reported in adult studies.Only one study on conventional pulpectomies was included in the review that reported a success rate of 36% for a small sample of patients (n = 10).No studies on apexification of molar teeth were included in the review. Therefore, further evidence is required to assess the success of this therapy.One case report showed success with regenerative endodontics for a single molar. Therefore, significant further evidence will be required to assess this approach.Conclusion The systematic review ascertained that partial and coronal pulpotomies had successful treatment outcomes for treating compromised first permanent molar teeth.


Identification of disulphide bonds in the refolding of bovine pancreatic RNase A.
Comprehension of the rules that govern the folding process is still far from satisfactory, though it is nevertheless clear that all the information required to define the folding is encoded in the amino acid sequence. In proteins that contain disulphide bonds, folding is associated with disulphide bond formation. Protein species with different numbers of disulphides tend to accumulate during the process; these species can be trapped in a stable form, by quenching any remaining free SH groups, and then characterized in order to identify the disulphide bonds formed. The refolding pathway of reduced and denatured RNase A has been studied using mass spectrometric strategies which allow identification of the formation and rearrangement of disulphide bonds during the process. When reoxidation was carried out in the presence of B M urea, producing the classic "scrambled' RNase, three native and 11 non-native disulphide bonds were identified. When the reoxidation was performed under nondenaturing conditions, the formation of several well defined non-native as well as native S-S bonds was observed at early stages of the refolding process. Under appropriate conditions, all four native disulphide bonds were identified at later stages of refolding and non-native disulphides were greatly diminished or non-existent. This stage corresponded with the almost complete recovery of biological activity of the protein. The results presented here show that both native and non-native disulphide bonds are formed during the refolding of reduced and denatured RNase A in vitro under different experimental conditions. Essentially 14 disulphide bonds were observed of the 2B theoretically possible cysteine couplings. Although this number constitutes a significant fraction of the theoretical total, the occurrence of only a subset of disulphides clearly indicates that the formation of the S-S bridges does not occur at random, even when reoxidation takes place under denaturing conditions.


Pomegranate seed oil influences the fatty acids profile and reduces the activity of desaturases in livers of Sprague-Dawley rats.
The aim of our study was to compare the influence of diet supplementation with pomegranate seed oil - as conjugated linolenic acids (CLnA) source, or conjugated linoleic acids (CLA) and to examine the mechanism of their activity. The content of fatty acids, levels of biomarkers of lipids' oxidation and the activity of key enzymes catalyzing lipids metabolism were measured. Obtained results revealed that conjugated fatty acids significantly decrease the activity of Δ5-desaturase (p=0.0001) and Δ6-desaturase (p=0.0008) and pomegranate seed oil reduces their activity in the most potent way. We confirmed that diet supplementation with pomegranate seed oil - a rich source of punicic acid leads to the increase of cis-9, trans-11 CLA content in livers (p=0.0003). Lack of side effects and beneficial influence on desaturases activity and fatty acids profile claim pomegranate seed oil to become interesting alternative for CLA as functional food.


Placental weight and placental weight to birthweight ratio in relation to Apgar score at birth: a population study of 522 360 singleton pregnancies.
To study whether placental weight or placental weight to birthweight ratio are associated with Apgar score in the newborn 5 min after birth. Population-based registry study. The Medical Birth Registry of Norway. All singleton live births during the period 1999-2008, a total of 522 360 births. The placental weight to birthweight ratios were divided into quartiles within 2-week intervals of gestational age at birth, hence 25% of the pregnancies were within each group. We studied the proportion of pregnancies in the highest quartile of placental weight and placental weight to birthweight ratio according to Apgar score 5 min after birth, and estimated the odds ratio for Apgar score ≤7 if the placental weight to birthweight ratio was in the highest quartile, and used the lowest quartile as reference. Apgar score in the newborn 5 min after birth. In births after pregnancy week 29, and at every 2-week gestational age interval, the mean placental weight and placental weight to birthweight ratio were higher in newborn with Apgar score ≤7 than in infants with Apgar >7. The crude odds ratio of Apgar score ≤7 was 1.65 (95% CI 1.57-1.74), comparing the highest to the lowest quartile of placental weight to birthweight ratio. Adjustments for gestational age, birthweight, infant sex, maternal age, preeclampsia, diabetes and congenital malformations did not alter the odds ratio significantly. Placental weight and placental weight to birthweight ratio were higher in pregnancies with infant Apgar score ≤7 compared with Apgar score >7.


Application of enterococci antibiotic resistance patterns for contamination source identification at Huntington Beach, California.
Huntington Beach, California, one of the most popular surfing spots in the world, is plagued by sporadic, elevated levels of fecal bacteria. To assist with pollution source identification, we analyzed antibiotic resistance patterns (ARPs) of enterococci from four known sources (bird feces, urban runoff, coastal marsh sediment and sewage effluent from local sanitation district) and one unknown source (seawater) using seven antibiotics at four concentrations each. Of 2491 enterococci tested, all were resistant to at least one antibiotic at some level. Discriminant analysis indicated that the average correct classification rates for bird feces and urban runoff sources were above 80%. Sewage effluent contained mixed fecal sources. Sixty-four percent of the sewage isolates classified with the sewage category, while the other 35% of isolates were assigned evenly across the other three categories. When enterococci isolated from the seawater were classified using the known ARP database, it was evident that bird feces were the source of surf zone contamination on some days while the coastal salt marsh and sewage plume may have impacted the surf zone water quality to various degrees during other times.


In situ photografting during direct laser writing in thermoplastic microchannels.
A method for in situ photografting during direct laser writing by two-photon polymerization is presented. The technique serves as a powerful approach to the formation of covalent bonds between 3D photoresist structures and thermoplastic surfaces. By leveraging the same laser for both pattern generation and localized surface reactions, crosslinking between the bulk photoresist and thermoplastic surface is achieved during polymerization. When applied to in-channel direct laser writing for microfluidic device fabrication, the process yields exceptionally strong adhesion and robust bond interfaces that can withstand pressure gradients as high as 7 MPa through proper channel design, photoinitiator selection, and processing conditions.


Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial.
The primary objective of this study is to evaluate the safety, tolerance, and pharmacokinetic profile of liver-directed therapy with drug-eluting beads irinotecan (DEBIRI) in combination with systemic modified FOLFOX in the treatment of unresectable liver metastases in chemotherapy-naive patients with colorectal cancer. DEBIRI, loaded with 100 mg irinotecan (100-300 μm beads), was administered via hepatic artery during the off week of FOLFOX therapy. Primary endpoints were safety, tolerance, systemic dose-limiting toxicities, and pharmacokinetics of systemic irinotecan and its active metabolite SN-38 at each infusion at 1-, 4-, and 24-h post-DEBIRI. Secondary endpoints were response rate and survival. The ten patients have undergone at least 12 cycles of FOLFOX in combination with at least two DEBIRI bead treatments during the patients' off week. Pharmacokinetic data has demonstrated minimal detectable levels of irinotecan (18.6, 21, and 18.6 ng/ml) and SN-38 (1.06, 1.47, and 1.55 ng/ml) after the first, second, and third DEBIRI treatments, respectively. Currently, there has been only one severe device-related adverse event, a grade 3 hypertensive episode that required 1 day of observation in the hospital. The initial 9- and 12-month response rates have been 100 % (2 CR, 8 PR). Four (40 %) patients were successfully downstaged to resection and/or ablation with a median overall survival of 15.2 months. Concomitant DEBIRI and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.


Sonochemically assisted 2,3-dideoxygenation and skeletal rearrangement of ecdysteroid derivatives.
Sonochemical 2,3-dideoxygenation of ecdysteroids with the Δ 2(3)-bond generation and activation of the C-C bonds of the steroid core in the poststerone derivatives, that causes the skeletal rearrangement have been carried out for the first time. Thus, the ultrasonically assisted reaction of 2,3-dimesyloxy derivatives of ecdysteroids with the NaI-Zn-DMF system gives rise to their 2,3-dideoxy-Δ2(3)-analogues with yields 70-92%. In the case of 2,3-dimesyloxypoststerone as the initial ecdysteroid substrate the reaction is accompanied by the activation of the allyl moiety and semipinacol rearrangement, resulting in the C13-C14 bond migration with C/D rings contraction/expansion and providing novel short chain (8R)-13(14 → 8)-abeo-isomer.


Binding of prednisolone and its ester prodrugs in the skin.
Skin binding of prednisolone and its esters was investigated in the hairless mouse skin in vitro. The distribution of the amount of drugs bound in the skin was determined by a skin slicing technique. The model drugs used were prednisolone (PN, M.W. 360) and its esters, senesyonate (PN-C5, M.W. 442), geranate (PN-C10, M.W. 510), farnesylate (PN-C15, M.W. 578), and geranylgeranate (PN-C20, M.W. 646). The distribution of bound drug was nonhomogeneous in the skin; the concentration of PN-C10 and PN-C15 in the skin increased gradually with the distance from the skin surface. The parent drug, PN, however, was hardly bound in the viable skin. These findings suggest that the prodrugs of prednisolone may prolong the dermal retention of the parent drug and minimize to delivery into the systemic circulation of the prodrug and metabolite.


Medical and surgical management for chronic thromboembolic pulmonary hypertension: a single center experience.
Pulmonary endarterectomy (PE) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to analyze our experience in the medical and surgical management of CTEPH. We included 80 patients diagnosed with CTEPH between January 2000 and July 2012. Thirty two patients underwent PE and 48 received medical treatment (MT). We analyzed functional class (FC), six-minute walking distance (6MWD) and pulmonary hemodynamics. Mortality in both groups and periods were analyzed. Patients who underwent PE were younger, mostly men, and had longer 6MWD. No differences were observed in pulmonary hemodynamics or FC at diagnosis. One year after treatment, all PE patients versus 41% in MT group were at FCI-II. At follow-up, the PE group showed greater increase in 6MWD, and greater reduction in mean pulmonary arterial pressure and pulmonary vascular resistance than the MT group (P<.05). Overall survival in the MT group at 1 and 5years was 83% and 69%, respectively. Conditional survival in patients alive 100days post-PE at 1 and 5years was 95% and 88%, respectively. Surgical mortality in operated patients in the first period (2000-2006) was 31,3%, and 6,3% in the second (2007-2012). PE provides good clinical results, and improves pulmonary hemodynamics in patients who successfully overcome the immediate postoperative period. After a learning period, the current operatory mortality in our center is similar to international standards.


The Clinical Value of Patient Home Videos in Movement Disorders.
Numerous studies have shown the value of patient home video recordings within the field of epilepsy. Despite the growing influence of mobile technology and telemedicine, there is a paucity of studies examining the role of home videos in the diagnosis of movement disorders. To characterize the clinical value of patient home videos in a movement disorders practice. We performed a retrospective review from our video database over the past 10 years and identified 20 encounters where an in-person, clinic evaluation and studio video were supplemented by a home video. We reviewed these encounters to determine if the home video added additional value to the clinic video. The home videos were screened by 3 movement disorders attendings and 3 movement disorders fellows to assess for quality and to determine whether or not the patient phenomenology could accurately be identified. Of the 20 videos identified, 10 (50%) were determined to be of additional clinical value. In 62.4% of evaluations movement disorders attendings and fellows were able to identify phenomenology from the home videos consistent with the final diagnosis. Videos rated as "poor" quality had significantly lower odds of leading to a correct phenomenology (odd ratio: 0.07, 95% confidence interval [0.01-0.72]) than those rated as "excellent" quality. Patients should be encouraged to produce good quality home videos, particularly in paroxysmal or fluctuating movement disorders, as they may add value to the eventual diagnosis and management.