The Ponseti Method for the Treatment of Clubfeet Associated With Down Syndrome: A Single-institution 18-year Experience.
Although the Ponseti method has been used with great success in a variety of nonidiopathic clubfoot deformities, the efficacy of this treatment in clubfeet associated with Down syndrome remains unreported. The purpose of this study is, therefore, to compare treatment characteristics and outcomes of clubfoot patients with Down syndrome to those with idiopathic clubfoot treated with the Ponseti method. An Institutional Review Board-approved, retrospective review of prospectively gathered data were performed at a single pediatric hospital over an 18-year period. Patients with either idiopathic clubfeet or clubfeet associated with Down syndrome who were less than 1 year of age at the outset of treatment were treated by the Ponseti method, and had a minimum of 2 year's follow-up were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified using the Richards classification system: "good" (plantigrade foot +/- heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release). Twenty clubfeet in 13 patients with Down syndrome and 320 idiopathic clubfeet in 215 patients were identified. Average follow-up was 73 months for the Down syndrome cohort and 62 months for the idiopathic cohort. Down syndrome patients presented for treatment at a significantly older age (61 vs. 16 d, P =0.00) and with significantly lower average initial Dimeglio scores than the idiopathic cohort (11.3 vs. 13.4, P =0.02). Heel cord tenotomy was performed in 80% of the Down syndrome cohort and 79% of the idiopathic cohort ( P =1.00). Recurrence rates were higher in the Down syndrome cohort (60%) compared with the idiopathic group (37%), but this difference was not statistically significant ( P =0.06). Need for later surgical procedures was similar between the 2 cohorts, though recurrences in the Down syndrome group were significantly less likely to require intra-articular surgery (8.3% vs. 65.5%, P =0.00). Clinical outcomes were 95% "good," 0% "fair," and 5% "poor" in the Down syndrome cohort and 69% "good," 27% "fair," and 4% "poor" in the idiopathic cohort ( P =0.01). Despite the milder deformity and an older age at presentation, clubfeet associated with Down syndrome have similar rates of recurrence and may have better clinical outcomes when compared with their idiopathic counterparts. When deformities do relapse in Down syndrome patients, significantly less intra-articular surgery is required than for idiopathic clubfeet. Level III.


Reference values for amino acids in cerebrospinal fluid of children determined using ion-exchange chromatography with fluorimetric detection.
One thousand specimens of CSF were collected from subjects ranging in age from newborn to 18 yr, who were undergoing a diagnostic lumbar puncture. Sixty-two samples were judged retrospectively as being suitable for calculating reference age-related values. The analyses were performed by an amino acid analyser using ion-exchange chromatography with fluorimetric detection giving a tenfold increase in sensitivity, thereby enhancing the diagnostic capabilities. As many as 36 known compounds could be detected, additionally 10 we could not identify. In children older than 3 yr nine of the identified compounds showed age-dependency. We found 22 amino acids to be significantly higher in infants younger than 1 yr, with only gamma-aminobutyric acid being significantly lower in infants. Alpha-aminoadipic acid showed a sex difference, being slightly higher in girls.


[International foreign bibliographic databases Medline and Internet Grateful Med V2.6. Presentation and how to use].
This paper aims to provide a practical kit in French for reference retrieval from the Internet using Medline and its specific software interface, Internet Grateful Med V2.6. This reference retrieval tool is now available to all end users via the Internet. We explain here how to use it, screen by screen and button by button.


Asymmetric copper-catalyzed fluorination of cyclic β-keto esters in a continuous-flow microreactor.
A highly enantioselective homogeneous fluorination of cyclic β-keto esters catalyzed by diphenylamine linked bis(oxazoline)-Cu(OTf)2 complexes has been established in a continuous flow microreactor. The microreactor allowed an efficient transformation with reaction times ranging from 0.5 to 20 min, and the desired products were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) at a low catalyst loading of 1 mol%.


In vitro control of growth and fumonisin production by Fusarium verticillioides and F. proliferatum using antioxidants under different water availability and temperature regimes.
To examine the effect of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trihydroxybutyrophenone and propylparaben (PP) (at concentrations of 1-20 mmol l(-1)) on growth of and fumonisin production by Argentinian strains of Fusarium verticillioides and F. proliferatum. Studies on lag phases prior to growth, relative growth rates and fumonisin concentrations were carried out in vitro in relation to water activity (0.995-0.93 a(w)) and temperature (18 and 25 degrees C) on a maize meal agar. Overall, PP was the antioxidant which was most effective at inhibiting strains of both species. The lag phase prior to growth and growth rates were significantly decreased by PP and BHA at 10 and 20 mmol l(-1), regardless of the temperature or aw level tested. Total fumonisin production was higher at 0.98 a(w) and decreased by about 45-50% at 0.995 and 0.95 a(w). Overall, BHT only inhibited fumonisin production at 0.95 aw at 10 and 20 mmol l(-1), while BHA was effective at most a(w) levels tested at 10 and 20 mmol l(-1). Propylparaben completely inhibited fumonisin production by both F. verticillioides and F. proliferatum at > 1 mmol l(-1), regardless of the temperature or a(w) level. Small interstrain differences in the levels of inhibition by the antioxidants were observed for three F. verticillioides and four F. proliferatum strains at 0.995, 0.98 and 0.95 a(w). Propylparaben and BHA completely inhibited the growth of both species at the concentrations evaluated, regardless of the a(w) level. Two antioxidants show promise for the control of growth of and fumonisin production by these species over a wide range of environmental conditions. Potential exists for using such food-grade preservatives for prevention of mycotoxigenic fungi and their toxins entering the food chain.


Electron energy loss spectroscopy investigation through a nano ablated uranium dioxide sample.
A lamella of uranium dioxide (∼10 × ∼10 × ∼0.02-0.20 μm) was produced by focused ion beam for transmission electron and electron energy loss spectroscopy (EELS) examinations. This sample allows quantitative analysis of the EEL spectra recorded for UO₂ as a function of the thickness. The M, N, O and P edges were recorded over zero loss to 4000 eV loss. The edges allow reconstruction of the electronic transitions, the lowest energy loss edges for P transitions corresponds to P3 electron transition (17.2 eV) from U6p3/2 level. The edge analysis allows also better interpretation of the loss spectrum with identification of the plasmon peak of the core electron transition edges. In addition, the energy lost was studied through a range of thicknesses going from ∼20 to ∼200 nm to derive the electron mean free path and cross section for inelastic scattering in the plasmon part of the spectrum. The mean free path of inelastic electron for uranium dioxide is compared with that reported earlier for other oxides from Be to Bi and for 200 keV incidents electrons. The present study emphasises the potential of combining FIB and EELS for the analysis of actinide compounds.


Ultrastructural observations on intercellular contacts of nigral dendrites.
Possible morphological correlates of dendritic release sites for dopamine have been investigated in the rat substantia nigra. Electronmicroscopic and freeze etching studies show that nigral dendrites fail to form dendrodendritic contacts but on the contrary are always separated by glial elements, which in turn are connected by multiple gap junctions. No dendro-axonic synapses are present but large specialized symmetrical junctions could provide a possible morphological specialization for a dopamine transfer from presynaptic dendrites to axon endings.


The oncogenic roles of NTRK fusions and methods of molecular diagnosis.
The NTRK gene family is composed of NTRK1, NTRK2, and NTRK3, which encode three tropomyosin-receptor kinases, belonging to a class of tyrosine kinase receptors. These proteins are known to play roles in cell proliferation, differentiation, apoptosis, and survival. Fusions involving the NTRK genes are long known as drivers in many tumors. Although they occur in less than 5% of all malignancies, their occurrence in a great diversity of tumors has been documented. Several rare tumors including infantile fibrosarcoma, secretory breast carcinoma, and mammary analogue secretory carcinoma are accompanied by NTRK fusions in more than 90% of cases, demonstrating a diagnostic value for the NTRK fusion testing in these tumors. More recently, the development of effective targeted therapies has created a demand for their detection in all malignancies. A variety of approaches are available for testing including immunohistochemistry, fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), and DNA- and RNA-based next-generation sequencing (NGS). This article reviews the molecular biology and tumorigenesis of NTRK fusions, their prevalence and clinical significance with a focus on available methods for fusion detection. The advantages and limitations of different technologies, the best practice algorithms for NTRK fusion detection, and the future direction of NTRK testing are also discussed.


Brainstem auditory evoked response and vestibulo-ocular reflex in severe head injury patients. A prospective study of 60 cases.
Brainstem auditory evoked response (BAER) performed in 60 serious head injury patients, over the last two year period at All India Institute of Medical Sciences, New Delhi have been analysed, to correlate the findings with ultimate outcome. All patients included in this study were unconscious, not following any command at the time of initial evaluation, mostly within 48 hours of injury. Repeat studies were performed in surviving patients. Computerized cranial tomography was performed to establish the nature of the intracranial pathology. The clinical status and cold caloric responses were recorded in all. The patients were followed up for 1 to 24 months. Three patients had extradural haematoma, 2 patients had subdural haematoma and 30 patients had intracerebral contusion/haematoma. Brain oedema was recorded in 14 cases. BAER was normal in 32 patients and 26 of them had good recovery (81%). Three patients with normal BAER died. Abnormal BAER was recorded in 21 patients and only 50% of them had good recovery and 25% of them died. In 7 patients BAER was absent and only 2 (29%) had a good recovery. Thus 48 out of 60 patients (66%) had a good recovery and 11 (18%) died. When compared to cold caloric response, 87% patients with normal caloric response had a good recovery and 5 out of 6 patients with absent caloric response died and remaining 1 left in a vegetative state. Thus the caloric response is at least as good a prognostic factor as BAER.


Better Together: Collaboration to Enhance the Nursing Workforce.
Nursing is a demanding profession that calls for nurses to devote time, energy, advocacy, and compassion to improving clients' lives while providing safe, efficient care. Nurses make personal sacrifices to meet their clients' needs, which do not come without costs to their well-being. An increased migration of novice nurses out of the profession and the need to increase the volume of the nursing workforce by an average of 8% annually to address the projected nursing shortage presents a compelling need for immediate action. Reimagining the concept of academic-service partnerships to provide exposure to opportunities that can equip and empower novice nurses as they emerge into professional practice cannot be underestimated. Implementing approaches to assess, support, and nurture the health and well-being of nurses and health care organizations is foundational to retention.


Progress and recent advances in phosphate sensors: a review.
This review covers the progress made in the development of sensors for inorganic and organic phosphates that are significant pollutants within the environmental and biological systems. Phosphate sensors in the forms of amperometric, potentiometric enzyme electrodes, plant tissue electrode and screen printed electrode are described. Instrumental probes such as fluorescence, chemiluminescence, luminescence and potentiometric ion selective electrodes are also described. Recent efforts on the use of voltammetric, potentiometric and amperometric biosensors for the determination of phosphate are highlighted.


Removal of Bilirubin with a New Adsorbent System: In Vitro Kinetics.
Many potentially toxic molecules accumulate in the blood during hepatic dysfunction. In clinical practice, it is very difficult to remove bilirubin, the most widely studied toxin, and particularly the unconjugated form, strongly albumin-bound. The aim of this in vitro study was to assess irreversible bilirubin adsorption as a protein-bound compound marker, using Cytosorb® (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines. We performed 4 in vitro experiments, dynamic and static, with different albumin-bilirubin solutions. All experiments showed the resin's ability to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin loss. No sign of bilirubin release from the charged resin was detected (Experiment 4). Cytosorb® seems a promising artificial liver support, thanks to its ability to adsorb bilirubin and its proven ability to modulate the cytokines involved in hepatic dysfunction.


[Mesenteric panniculitis as the initial manifestation of a B cell lymphoma].
Mesenteric panniculitis is an uncommon clinical entity which sometimes may be associated with hematologic, gastrointestinal and urological neoplasms. The diagnostic procedure ofchoice is based on obtaining a tissue sample for histopathological study usually through apercutaneous procedure. Treatment is indicated in symptomatic cases.


Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study.
The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population. In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16-99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence. Between June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16-0·19, p<0·001). Sore throat was more common during omicron prevalence than during delta prevalence (70·5% vs 60·8%, 1·55; 1·43-1·69, p<0·001). There was a lower rate of hospital admission during omicron prevalence than during delta prevalence (1·9% vs 2·6%, OR 0·75; 95% CI 0·57-0·98, p=0·03). The prevalence of symptoms that characterise an omicron infection differs from those of the delta SARS-CoV-2 variant, apparently with less involvement of the lower respiratory tract and reduced probability of hospital admission. Our data indicate a shorter period of illness and potentially of infectiousness which should impact work-health policies and public health advice. Wellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, and Medical Research Council.


The role of under-employment and unemployment in recent birth cohort effects in Australian suicide.
High suicide rates evident in Australian young adults during an epidemic period in the 1990s appear to have been sustained in older age-groups in the subsequent decade. This period also coincides with changes in employment patterns in Australia. This study investigates age, period, and birth cohort effects in Australian suicide over the 20th century, with particular reference to the period subsequent to the 1990s youth suicide epidemic in young males. Period- and cohort-specific trends in suicide were examined for 1907-2010 based on descriptive analysis of age-specific suicide rates and a series of age-period-cohort (APC) models using Poisson regression. Under-employment rates (those employed part-time seeking additional hours of work) and unemployment rates (those currently seeking employment) for the latter part of this time series (1978-2010) were also examined and compared with period- and cohort-specific trends in suicide. A significant increasing birth cohort effect in male suicide rates was evident in birth cohorts born after 1970-74, after adjusting for the effects age and period. An increasing birth cohort effect was also evident in female suicide rates, but was of a lesser magnitude. Increases in male cohort-specific suicide rates were significantly correlated with increases in cohort-specific under-employment and unemployment rates. Birth cohorts that experienced the peak of the suicide epidemic during the 1990s have continued to have higher suicide rates than cohorts born in earlier epochs. This increase coincides with changes to a labour force characterised by greater 'flexibility' and 'casualised' employment, especially in younger aged cohorts.


Plasma nitric oxide and iron concentrations in exercised rats are negatively correlated.
The aim of this study was to investigate the effect of strenuous exercise on plasma nitric oxide and iron (PI) concentrations in rats. The rats were divided into six groups: 3, 6 and 12 months of the exercise (swimming) groups and their corresponding controls. At the end of experimental periods, blood samples were collected to measure plasma NOx (nitrate and nitrite) and iron concentrations and other hematological indices. The correlative analysis of plasma NOx with PI in the exercised and the control rats was performed. The results showed that plasma NOx concentration was significantly greater and PI lower in the 3, 6, and 12 months of the exercise groups compared to their sedentary controls (p < 0.01). However, the duration of strenuous exercise had no significant effect on plasma NOx or PI contents. A negative correlation between plasma NOx and PI levels was found in all three exercise groups (r = -0.750, -0.578, and -0.808 and p < 0.01, 0.05, 0.01 respectively), but not in the sedentary control groups. These results imply that strenuous exercise may lead to an increase in plasma NOx concentration as well as a low iron level. They also suggest the possibility that the increased NO production might be associated with the development of the lower iron status in exercise.


Determination of the absolute configuration of a key tricyclic component of a novel vasopressin receptor antagonist by use of vibrational circular dichroism.
We present the results of a study using vibrational circular dichroism (VCD) for (+)-1, which furnished an unambiguous determination of its absolute configuration as S. The most abundant conformation of (+)-1 in CDCl(3) solution was also established.


Central terminations of periodontal mechanoreceptive and tooth pulp afferents in the trigeminal principal and oral nuclei of the cat.
Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed to define the response properties of low-threshold mechanoreceptive periodontal afferents and of the tooth pulp afferents and the morphological characteristics of their axon arbors in the nucleus principalis (Vp) and rostrodorsomedial (Vo.r) and dorsomedial parts (Vo.dm) of the nucleus oralis (Vo). The central terminals of 3 fast adapting (FA) and 4 slowly adapting (SA) periodontal afferents and 4 tooth pulp (TP) afferents were recovered for detailed analyses. Stained axons in the trigeminal sensory tract ascended and descended (bifurcating fibers), or descended without bifurcation (descending non-bifurcating fibers). The ratio of the bifurcating fibers to the descending non-bifurcating fibers was about three to one for each type of afferents. The main collaterals given off from the ascending branches terminated in the Vp. Most collaterals given off from the descending branches terminated in the Vo with the exception of few instances. In case of the FA afferents, the ascending branches gave off all main collaterals into the Vp with rostrocaudal and dorsoventral continuities in their arbors, whereas the descending branches gave off all main collaterals, except two collaterals, into the Vo with rostrocaudal discontinuities. The projections from the FA afferents to the Vo.dm was predominant in terms of the number of boutons and the length of preterminal and terminal branches. In case of the SA afferents, the collaterals from the ascending and descending branches formed rostrocaudally and dorsoventrally discontinuous terminal arbors. In terms of the density of boutons the SA afferents were divided into two subtypes. One had a preferential projection into the Vp or Vo, whereas others lacked a selective projection. In case of the TP afferents, the main collaterals of the ascending branches formed partially overlapping terminal arbors, but the terminal arbors formed by the collateral of the descending branches did not overlap. The frequency of collaterals of the TP afferents was less than that of the other types of afferents. The terminal arbors including the density of boutons of the pulpal afferents were less extensive than those of the other types of afferents. The average size of varicosities became smaller in the following subdivisions. Vp, Vo.r and Vo.dm for SA and TP afferents. The size of varicosities of the TP afferents was smaller and that of the FA afferents was larger than that of the SA afferents.(ABSTRACT TRUNCATED AT 400 WORDS)


Postthoracotomy pain management problems.
Pain after thoracotomy is very severe, probably the most severe pain experienced after surgery. Thoracic epidural analgesia has greatly improved the pain experience and its consequences and has been considered the standard for pain management after thoracotomy. This view has been challenged recently by the use of paravertebral nerve blocks. Nevertheless, severe ipsilateral shoulder pain and the prevention of the postthoracotomy pain syndrome remain the most important challenges for management of postthoracotomy pain.


In-vivo and human evidence for potential efficacy of therapeutic polyclonal RSV neutralizing antibodies for palivizumab-resistant RSV infections.
Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®, RI-001, RI-002) are used with ribavirin in RSV-infected immunocompromised patients, with debated efficacy. Palivizumab-resistance (PR) can arise during treatment of persistent infections in this population. RSV-IG may confer benefit in PR-RSV infection. RSV-IG [RI-001] was provided for an immunocompromised infant with RSV-pneumonitis refractory to ribavirin and palivizumab. RSV-neutralizing antibody, respiratory RSV load (qPCR), and F-gene-sequence-detection of PR was determined. Prophylactic RSV-IG [RI-002] or palivizumab was administered in a cotton-rat model infected with wild-type and PR-RSV. Lung RSV load and neutralizing antibody were measured. As protective RI-001-neutralizing antibody titers waned in the infant, a subpopulation of PR-escape mutants were detected with a fatal RSV-burden in the lungs. In PR-RSV-infected cotton rats, prophylactic RI-002 reduced RSV-load in the lungs (2.45 vs 0.28 log10 PFU/g lung-tissue reduction, respectively, p < 0.05) and provided protective RSV-neutralizing antibody. RSV-IG and ribavirin use in immunocompromised patients requires further study.


Role of c-Fos protein on glutamate toxicity in primary neural hippocampal cells.
The hippocampus is extremely sensitive to microenvironmental signals and toxic events, including massive glutamate release. Despite the extensive literature related to the cascade of molecular events triggered in postsynaptic neurons, the distinction between proapoptotic and survival pathways is still being discussed. In this study, we have investigated the role of c-Fos in glutamate-induced toxicity in primary cultures of hippocampal neurons by using antisense oligonucleotide (ASO) technology. Exposure of cells (5 days in vitro; DIV) to glutamate 0.5 mM for 24 hr caused massive nuclear alteration. An increase in the number of caspase-3-positive cells was also observed 24 hr after glutamate treatment. The expression of c-fos and c-jun immediate-early genes was increased 30 min after glutamate exposure. The study of c-Fos and c-Jun protein expression revealed an increase in the number of cells positive for both antibodies. To investigate whether the expression of c-Fos protein after glutamate treatment was related to cell death activation or cell survival pathways, cells were exposed to 5 microM of c-fos ASO at 4 DIV, 24 hr before glutamate treatment. The presence of the ASO in the medium significantly decreased the number of altered nuclei, and this was associated with a significant reduction in the number of c-Fos-positive cells after glutamate treatment. Exposure of cells to the c-fos ASO under the conditions described above decreased caspase-3 immunostaining induced by glutamate. These results suggest that the synthesis of c-Fos protein after glutamate exposure favors cell death pathway activation in which caspase-3 is also involved.


Design and serendipity in the path to prostaglandins.
Leon Wolfe was a brilliant scientist who was gifted with curiosity and drive. This personal account touches on salient events in a rewarding collaboration and lifelong friendship, starting from the original identification of prostaglandin as a natural neurohumoral agent and progressing with the unpredictable developments of this research beyond the brain. Design and serendipity are the leitmotifs in an exciting story unfolding over the years.


The effect of calcium concentration on spontaneous ventricular defibrillation and VF threshold.
In order to investigate the influence of the effective refractory period on spontaneous ventricular defibrillation, isolated rat hearts were perfused with Krebs-Henseleit solution containing 0.5, 2.7 and 5.1 mM calcium. After measuring the fibrillation threshold at spontaneous rate (SR), ventricular fibrillation (VF) was induced during basic ventricular pacing of 110% SR, or the highest rate permitting 1:1 electromechanical coupling. The VF threshold was significantly reduced from 13.6 +/- 3.5 to 7.9 +/- 5.3 and 5.1 +/- 3.4 mA at 0.5, 2.7 and 5.1 mM Ca++ concentrations, respectively. The incidence of spontaneous recovery from VF, induced during basic pacing, was 100%, 83% and 50% at calcium concentrations of 0.5, 2.7 and 5.1 mM, respectively, (p less than 0.01 for the incidences at 0.5 mM versus 5.1 mM Ca++). The incidence of spontaneous defibrillation decreased when the hearts were driven rapidly, with spontaneous recovery rates of 92%, 58% and 0% (p less than 0.0001] for corresponding increases in Ca++ concentration. Induced ventricular fibrillation of fine morphology was frequently observed at 5.1 mM Ca++. It appears that progressive impairment of spontaneous defibrillation is caused by an increase in calcium concentration, this effect being more pronounced at high ventricular rates. Variations in the effective refractory period, caused by alterations in extracellular calcium concentration and differences in intracellular Ca++ accumulation, may account for the above results.


Serum oestrone, oestradiol and oestriol concentrations during oral oestradiol valerate and oestriol succinate therapy in ovariectomized women.
Serum oestrone, oestradiol and oestriol concentrations were investigated during oral treatment with oestradiol valerate and oestriol succinate in ovariectomized women. The dosages used were 1 mg oestradiol valerate in the morning and 2 mg oestriol succinate in the evening of the first day and 2 mg oestradiol valerate in the morning of the second day of treatment. The other group of patients received the same therapy in reverse order. The variation in the serum oestrone and oestradiol concentrations with a daily dose of 1 or 2 mg of oestradiol valerate were considerable. 2 mg oestriol succinate caused a fairly small elevation of serum oestriol concentration. In both treatment groups the quotient E3/(E2 + E1) was similar to that found at the 6-7th day and in the middle of the normal menstrual cycle, the quotient E1/(E2 + E3) was somewhat higher than during normal cycle.


Early essential newborn care is associated with increased breastfeeding: a quasi-experimental study from Sichuan Province of Western China.
Breastfeeding is critical to promote maternal and child health. China has set national targets to further improve the exclusive breastfeeding rate. We aimed to examine associations between the provision of early essential newborn care (EENC) and breastfeeding outcomes among full term vaginally delivered neonates in the first 6 months of life. We conducted a quasi-experimental study in eight maternal and children's hospitals in Mianyang City and Deyang City in Sichuan Province of western China. Four hospitals were randomly selected as the intervention group with the implementation of EENC while others as the control group receiving routine care. We assessed effects of EENC on breastfeeding initiation time, duration of first-time breastfeeding, and exclusive breastfeeding rates up to 6 months of age. Data were collected after delivery, at hospital discharge, 1 month, 3 months, and 6 months post birth in the baseline phase from May to June 2017 and post-EENC phase from October to December 2017. We performed univariate analyses to ascertain differences between the two groups, and difference in difference (DID) models to explore the net effects. Of the 1349 enrolled mother and newborn pairs in our study, 1131 (83.9%) were followed up at 1 month of age, 1075 (79.7%) at 3 months, and 981 (72.7%) at 6 months. EENC was associated with earlier median time to initiate breastfeeding (25 min vs. 33 min, P < 0.01), an increased chance of successful first-time breastfeeding (OR 5.53; 95% CI 2.69, 11.40), longer duration of skin to skin contact (SSC) (21.53 min; 95% CI 18.17, 24.89) and longer duration of the first breastfeed (4.16 min; 95% CI 2.10, 6.22), and an increased likelihood of being exclusively breastfed at discharge (74.5% vs. 55.0%, P < 0.001), 3 months (OR 3.20; 95% CI 1.01, 10.15), and 6 months (OR 4.91; 95% CI 1.71, 14.13) of age. EENC enhances breastfeeding initiation and increases exclusive breastfeeding at 6 months of age. Our evidence suggests that nationwide scale up of EENC would increase the exclusive breastfeeding rate in the first 6 months of life.


Identification of novel mechanisms of silymarin on the carbon tetrachloride-induced liver fibrosis in mice by nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis.
In this study, we applied bioluminescent imaging-guided transcriptomic analysis to evaluate and identify the therapeutic potentials and novel mechanisms of silymarin on carbon tetrachloride (CCl(4))-induced liver fibrosis. Transgenic mice, carrying the luciferase genes driven by nuclear factor-κB (NF-κB), were given with CCl(4) and/or silymarin. In vivo NF-κB activity was evaluated by bioluminescent imaging, liver fibrosis was judged by Sirius red staining and immunohistochemistry, and gene expression profiles of silymarin-treated livers were analyzed by DNA microarray. CCl(4) enhanced the NF-κB-dependent hepatic luminescence and induced hepatic fibrosis, while silymarin reduced the CCl(4)-induced hepatic luminescence and improved CCl(4)-induced liver fibrosis. Microarray analysis showed that silymarin altered the transforming growth factor-β-mediated pathways, which play pivotal roles in the progression of liver fibrosis. Moreover, we newly identified that silymarin downregulated the expression levels of cytoskeleton organization genes and mitochondrion electron-transfer chain genes, such as cytochrome c oxidase Cox6a2, Cox7a1, and Cox8b genes. In conclusion, the correlation of NF-κB-dependent luminescence and liver fibrosis suggested the feasibility of NF-κB bioluminescent imaging for the evaluation of liver fibrosis progression and therapeutic potentials. Moreover, our findings suggested that silymarin might exhibit anti-fibrotic effects in vivo via altering the expression of genes involved in cytoskeleton organization and mitochondrion electron-transfer chain.


Ketosis-Prone Type 2 Diabetes: A Case Series.
Ketosis-prone type 2 diabetes ("Flatbush diabetes") carries features of both classical type 1 and type 2 diabetes and is highly prevalent in African populations. The disease, which is highly ketosis-prone, but neither chronically insulinopenic nor autoimmune, is discussed regarding pathogenesis, diagnosis and treatment from a patient case perspective.


Challenges and Opportunities for Applying Wearable Technology to Sleep.
Wearable technology has a history in sleep research dating back to the 1970s. Because modern wearable technology is relatively cheap and widely used by the general population, this represents an opportunity to leverage wearable devices to advance sleep medicine and research. However, there is a lack of published validation studies designed to quantify device performance against accepted gold standards, especially across different populations. Recommendations for conducting performance assessments and using wearable devices are now published with the goal of standardizing wearable device implementation and advancing the field.


Glucose production rates in type 1 glycogen storage disease.
Glucose production rates were measured in six patients with glycogen storage disease type 1 (five type 1A, one type 1B) using a primed continuous infusion of either [3-3H]glucose or [6,6-2H2]glucose. In four patients exogenous glucose was needed to maintain normoglycaemia. At blood glucose concentrations of 2.3-4.7 mmol/L, the endogenous glucose production rates were between 34 and 100% of that predicted for healthy subjects. No relationship was found between the blood glucose concentration and glucose production rates but there was a positive correlation between that of blood lactate and glucose production rate. The initial steady state was perturbed either by reducing the exogenous glucose infusion rate or by giving intravenous glucagon (20 micrograms/kg) or alanine (0.1-0.2 g/kg). Reducing the exogenous glucose infusion rate had little short term effect on glucose production rate. Intravenous glucagon increased the glucose production rate as well as blood glucose and lactate concentrations. A bolus of alanine (0.2 g/kg) given intravenously increased the glucose production rate and blood glucose concentrations but blood lactate concentrations fell. In four of the patients the studies were repeated under similar conditions and the glucose production rate was higher in all patients. We conclude that the glucose production rate is not fixed but varies with the prevailing metabolic status, a finding that has implications for the treatment of type 1 glycogen storage disease.


Rlm1 mediates positive autoregulatory transcriptional feedback that is essential for Slt2-dependent gene expression.
Activation of the yeast cell wall integrity (CWI) pathway induces an adaptive transcriptional programme that is largely dependent on the transcription factor Rlm1 and the mitogen-activated protein kinase (MAPK) Slt2. Upon cell wall stress, the transcription factor Rlm1 is recruited to the promoters of RLM1 and SLT2, and exerts positive-feedback mechanisms on the expression of both genes. Activation of the MAPK Slt2 by cell wall stress is not impaired in strains with individual blockade of any of the two feedback pathways. Abrogation of the autoregulatory feedback mechanism on RLM1 severely affects the transcriptional response elicited by activation of the CWI pathway. In contrast, a positive trans-acting feedback mechanism exerted by Rlm1 on SLT2 also regulates CWI output responses but to a lesser extent. Therefore, a complete CWI transcriptional response requires not only phosphorylation of Rlm1 by Slt2 but also concurrent SLT2- and RLM1-mediated positive-feedback mechanisms; sustained patterns of gene expression are mainly achieved by positive autoregulatory circuits based on the transcriptional activation of Rlm1.


Electromyography of masticatory muscles in three jaw registration positions.
The purpose of this study was to investigate whether anteroposterior changes in mandibular position affect masticatory muscle activity. The electromyographic (EMG) activity of masticatory muscles during full and partial (10%) clenching in three mandibular bite registration positions--retruded contact position (RCP), intercuspal position (IP), and muscular position (MP)--was studied. Three groups of subjects with different ranges of anteroposterior positioning of the condyles were evaluated (normal occlusion, Class II, Division 2 malocclusion, and dual bite malocclusion). A posterior stabilizing splint for each registration position was made. EMG data were obtained from three bilateral muscles (masseter, anterior temporal, and posterior temporal). Clenching in the RCP elicited the lowest masseter muscle activity during full clenching, and the highest anterior temporal and posterior temporal muscle activity during partial clenching. If the relationships of the masticatory muscles are analyzed through a ratio that represents the interaction between biting and positioning muscles (masseter/posterior temporal muscle ratio), the RCP as compared with other positions had the lowest ratio. The RCP required more positioning muscle activity and permitted less biting muscle activity. There was no significant difference in the muscle activity between the IP and MP registrations. Small changes in jaw position (anterior to RCP) are not critical for the masticatory apparatus provided there is good intercuspation. The results of this investigation suggest that intercuspation in RCP is not the optimal position.


Age-Related Changes in the Spatial Variation of Magnetic Susceptibility of Human Articular Cartilage.
Quantitative susceptibility mapping (QSM) has shown great potential for revealing the layer structure of articular cartilage based on the laminar susceptibility difference at different depths. However, more information is needed on the effects of age on the spatial distribution of magnetic susceptibility in human cartilage. To assess the ability of QSM to quantify the age-related differences in depth-wise cartilage susceptibility values in healthy populations. Prospective. A total of 94 healthy asymptomatic subjects in three age cohorts: 19-30 (n = 36, 20 males), 31-50 (n = 45, 27 males), and 51-66 years (n = 13, 7 males). 3D gradient echo sequences at 3.0 T. Four cartilage compartments were analyzed, including the central lateral/medial femur (cLF/cMF) and the lateral/medial tibia (LT/MT). The spatial susceptibility profile and the corresponding 95% confidence interval (CI) of each age cohort were obtained as functions of the normalized distance from the bone-cartilage interface to the cartilage surface (cartilage depth from 0.0 to 1.0). The relationship between age and cartilage thickness of each cartilage subregion was tested by Pearson correlation with P < 0.05 considered significant. Cartilage depths with separations of 95% CIs were considered to have significant susceptibility differences between two age cohorts with a Bonferroni-corrected P < 0.05. The cartilage thickness did not change significantly with age (P value range: 0.06-0.85). Susceptibilities were significantly higher in the 51-66-year-olds compared with the 31-50-year-olds in the deep layer of cMF (cartilage depth: 0.0-0.22) and LT (0.05-0.28). Susceptibilities were significantly higher in the 51-66-year-olds compared with the 19-30-year-olds near the cartilage-bone interface of cMF (0.0-0.34), cLF (0.0-0.28), and LT (0.0-0.58). There were also significantly higher susceptibilities in the 31-50-year-olds compared with the 19-30-year-olds in the deeper regions of cMF (0.26-0.57), cLF (0.0-0.40), and LT (0.07-0.80). Age-related susceptibility changes in the deeper regions of knee cartilage were observed using QSM. 2 TECHNICAL EFFICACY: Stage 2.


Is long-term sonographic followup necessary after uncomplicated ureteral reimplantation in children?
We examined the necessity of postoperative ultrasound following surgical correction of vesicoureteral reflux beyond initial postoperative assessment. The followup among children who have undergone correction of vesicoureteral reflux has varied, and currently there are no standards to document how long postoperative monitoring for hydronephrosis, renal scarring or renal growth should continue. The study population included 128 children who underwent surgical correction of primary vesicoureteral reflux between 1992 and 2002. Data were collected as part of a retrospective chart review and included age at surgery, preoperative grade of reflux, indications for surgery, type of surgical correction, postoperative voiding cystourethrogram and ultrasound results, and postoperative course relative to urinary tract infections, incontinence and other symptoms. Of 128 patients 4 had postoperative reflux on voiding cystourethrogram. In each of these cases reflux either resolved completely or remained stable during postoperative followup. A total of 17 patients had grade 2 or 3 hydronephrosis on the initial 3-month postoperative ultrasound. In all of these cases hydronephrosis remained stable or improved during followup. In no case was there evidence of development of new hydronephrosis or worsening of previously established hydronephrosis beyond the 1-year postoperative ultrasound. Our data indicate that followup of uncomplicated ureteral reimplantation in children more than 1 year postoperatively is not warranted. The elimination of studies beyond 1 year following surgery would result in a significant cost savings.


Development of cell culture (MDCK) live cold-adapted (CA) attenuated influenza vaccine.
Optimal conditions are determined for growing cold-adapted reassortant strains of a live influenza vaccine in MDCK cell line cultivated in a fermenter with a serum-free medium and microcarriers. The studied MDCK cell line meet all national and WHO requirements for the finite cell lines used for the production of biological preparations. CA reassortant vaccine strains grown in such conditions which fully preserve its mutations and the mutations lead to amino acid substitution in all genome segments of the studied CA reassortants. Under optimal cultivation conditions, the output of a monovalent live CA influenza vaccine in a 10-l fermenter may reach 100,000 doses.


Postmeiotic development of pollen surface layers requires two Arabidopsis ABCG-type transporters.
Two Arabidopsis ABC transporters, ABCG1 and ABCG16, are expressed in the tapetal layer, specifically after postmeiotic microspore release, and play important roles in pollen surface development. The male gametophytic cells of terrestrial plants, the pollen grains, travel far before fertilization, and thus require strong protective layers, which take the form of a pollen coat and a pollen wall. The protective surface structures are generated by the tapetum, the tissue surrounding the developing gametophytes. Many ABC transporters, including Arabidopsis thaliana ABCG1 and ABCG16, have been shown to play essential roles in the development of such protective layers. However, the details of the mechanism of their function remain to be clarified. In this study, we show that ABCG1 and ABCG16 are localized at the plasma membrane of tapetal cells, specifically after postmeiotic microspore release, and play critical roles in the postmeiotic stages of male gametophyte development. Consistent with this stage-specific expression, the abcg1 abcg16 double knockout mutant exhibited defects in pollen development after postmeiotic microspore release; their microspores lacked intact nexine and intine layers, exhibited defects in pollen mitosis I, displayed ectopic deposits of arabinogalactan proteins, failed to complete cytokinesis, and lacked sperm cells. Interestingly, the double mutant exhibited abnormalities in the internal structures of tapetal cells, too; the storage organelles of tapetal cells, tapetosomes and elaioplasts, were morphologically altered. Thus, this work reveals that the lack of ABCG1 and ABCG16 at the tapetal cell membrane causes a broad range of defects in pollen, as well as in tapetal cells themselves. Furthermore, these results suggest that normal pollen surface development is necessary for normal development of the pollen cytoplasm.


Prevention of radiation-induced cancers.
The issue of radiation-induced cancers must be taken into consideration during therapeutic irradiations. Risk factors for radiation-induced cancer include: the age of the patients, the volumes irradiated, the presence of risk cofactors and the exposure of critical organs. Those should be part of the therapeutic decision, in terms of indication, as well as choice of the radiotherapy technique (including repositioning systems). We present the update of the recommendations of the French society for radiation oncology on the modalities for preventing radiation-induced cancers.


High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females.
Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min- 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.


A general method for the creation of dilational surfaces.
Dilational structures can change in size without changing their shape. Current dilational designs are only suitable for specific shapes or curvatures and often require parts of the structure to move perpendicular to the dilational surface, thereby occupying part of the enclosed volume. Here, we present a general method for creating dilational structures from arbitrary surfaces (2-manifolds with or without boundary), where all motions are tangent to the described surface. The method consists of triangulating the target curved surface and replacing each of the triangular faces by pantograph mechanisms according to a tiling algorithm that avoids collisions between neighboring pantographs. Following this algorithm, any surface can be made to mechanically dilate and could, theoretically, scale from the fully expanded configuration down to a single point. We illustrate the method with three examples of increasing complexity and varying Gaussian curvature.


Trypanosoma cruzi: surface antigenic determinants.
A fraction (FAd) capable of inhibiting specific agglutination reactions of anti-epimastigote sera (anti-LE) was obtained by extracting the sediment of lyophilized epimastigote lysates (LE) with 0.05 M phosphate buffered saline, at 37 degrees C for 1 h. These conditions favored the action of parasite proteinase whose presence was detected by tandem-crossed immunoelectrophoresis experiments. As expected from the proteinase properties, the addition of 2-mercaptoethanol or sodium iodoacetate to the extracting solution resulted, respectively, in either increased or decreased amounts of protein in the resulting FAd. FAd components could be precipitated by the addition of Concanavalin A, methylated albumins or 0.1 N HCl. This fraction presented a single component when subjected to electrophoresis in 1% agarose gel with an electrophoretic mobility 1.2 times higher than that of human albumin. FAd component(s) were unable to penetrate 15% polycrylamide gel matrix unless 1% SDS was used. Under this condition four glycopeptide components, with Rm of 0.5, 0.55, 0.6 and 0.86, were detected. The antigenic determinants present in FAd resisted heating at 100 degrees C for 30 min and the prolonged action of pronase. However, these determinants were completely destroyed by the action of 25 mM sodium periodate, thus suggesting polysaccharide characteristics. Immunization of rabbits with FAd induced the production of antibodies that were unable to precipitate with either FAd or with parasite proteinase. These antibodies exhibited positive agglutination reactions with epimastigote forms and positive immunofluorescence and immunoperoxidase reactions with trypomastigote and amastigote forms of the different strains tested. FAd was able to inhibit these reactions as well as those obtained with anti-LE and anti-FA immune sera, whereas purified proteinase was unable to inhibit any of these reactions.


SOD3 Is Secreted by Adipocytes and Mitigates High-Fat Diet-Induced Obesity, Inflammation, and Insulin Resistance.
Aims: To study the expression and regulatory role of SOD3 in adipocytes and adipose tissue. Results: SOD3 expression was determined in various tissues of adult C57BL/6J mice, human adipose tissue and epididymal adipose tissue, subcutaneous adipose tissue and brown adipose tissue of high-fat diet (HFD)-induced obese mice. SOD3 expression and release were evaluated in adipocytes differentiated from primary human preadipocytes and murine bone marrow-derived mesenchymal stem cells (BM-MSCs). The regulatory role for SOD3 was determined by SOD3 lentivirus knockdown in human adipocytes and global sod3 knockout (KO) mice. SOD3 was expressed at high levels in white adipose tissue, and adipocytes were the main cells expressing SOD3 in adipose tissue. SOD3 expression was significantly elevated in adipose tissue of HFD-fed mice. Moreover, SOD3 expression and release were markedly increased in differentiated human adipocytes and adipocytes differentiated from mouse BM-MSCs compared with undifferentiated cells. In addition, SOD3 silencing in human adipocytes increased expression of genes involved in lipid metabolic pathways such as PPARγ and SREBP1c and promoted the accumulation of triglycerides. Finally, global sod3 KO mice were more obese and insulin resistant with enlarged adipose tissue and increased triglyceride accumulation. Innovation: Our data showed that SOD3 is secreted from adipocytes and regulates lipid metabolism in adipose tissue. This important discovery may open up new avenues of research for the cytoprotective role of SOD3 in obesity and its associated metabolic disorders. Conclusion: SOD3 is a protective factor secreted by adipocytes in response to HFD-induced obesity and regulates adipose tissue lipid metabolism.


Successful Thrombolysis in the Setting of Marfan Syndrome and Chronic Aortic Dissection.
Thrombolysis is the standard of care in acute ischemic stroke. It is usually contraindicated in patients with aortic dissection. We report a case of Marfan syndrome and chronic aortic dissection presenting with acute ischemic stroke treated with thrombolysis. To our knowledge, this is the first case of Marfan syndrome with chronic aortic dissection undergoing thrombolysis for acute ischemic stroke with a near-complete recovery of neurological deficit and favorable long-term outcome.


[Incidence and characteristics of pancreatic cystic neoplasms].
Cystic neoplasms (CN) of the pancreas represent 10% of cystic lesions and 1% of pancreatic tumors. Mucinous cystic neoplasm (MCN), serous cystadenoma (SC) and intraductal papillary mucinous neoplasm (IPMN) are cystic neoplasms and represent more than 90% of these types of lesion. Few series have been published on these lesions, especially in Spain. To evaluate the incidence, characteristics and survival of patients with cystic neoplasms attended in our hospital in the last 12 years. A retrospective analysis was carried out in all patients diagnosed with CN between January 1997 and December 2008. Diagnosis was made by abdominal computed tomography, pancreatic-magnetic resonance imaging and/or endoscopic ultrasonography. Sex, age, year of diagnosis, symptoms, tumoral location and size, type of surgery, pathology, and survival were evaluated. A total of 117 patients were analyzed. The mean age was 63±14 years and 56% were women. Eighty-eight patients had IPMN, 21 had SC and eight had MCN. Fifty-six per cent were diagnosed in the last 4 years, 42.7% were diagnosed as an incidental finding and 19% had a history of acute pancreatitis. The most frequent location was the pancreatic head (53%). The mean imaging size was 32mm. Surgical resection was performed in 69.2% of the patients. Twenty-three percent of the tumors were malignant, 30% were carcinoma in situ and 70% were invasive. Thirteen percent of the patients died; of these 93.3% had invasive carcinoma. Five-year survival was 94.7% in SC, 76% in IPMN and 60% in MCN. CN were mainly identified as incidental findings, although acute pancreatitis is another possible cause. The most frequent tumor in our environment is IPMN. Surgical treatment of IPMN and MCN, at the right moment, may be useful to prevent the development of pancreatic carcinoma.


Sex and age differences in the association of fatty liver index-defined non-alcoholic fatty liver disease with cardiometabolic risk factors: a cross-sectional study.
Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults. This cross-sectional study included data from 33,216 Spanish adult workers (18-65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression. The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3-28.5%) for men and 6.8% (95% CI 6.4-7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses. Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.


"Evidence-based Tweeting" in Vascular Surgery.
The use of social media for academic or research purposes is still in infancy. However, the potential of dissemination of medical knowledge through these electronic platforms is dynamically increasing. We performed a search on Twitter® collecting tweets containing the keywords "peripheral arterial disease" and "abdominal aortic aneurysm" separately and including 3 types of emitters. Our aim was to assess the dissemination of these 2 major vascular entities across the social networking and their effect on the medical and general population. The results show that people talk about their experiences of hospitals and care quality on Twitter® more than health care providers or commercial industries in critical diseases that arise more concern. Twitter® could become a successful channel through which physicians, patients, and health care providers interact, engage, and disseminate medical knowledge.


Observed deep energetic eddies by seamount wake.
Despite numerous surface eddies are observed in the ocean, deep eddies (a type of eddies which have no footprints at the sea surface) are much less reported in the literature due to the scarcity of their observation. In this letter, from recently collected current and temperature data by mooring arrays, a deep energetic and baroclinic eddy is detected in the northwestern South China Sea (SCS) with its intensity, size, polarity and structure being characterized. It remarkably deepens isotherm at deep layers by the amplitude of ~120 m and induces a maximal velocity amplitude about 0.18 m/s, which is far larger than the median velocity (0.02 m/s). The deep eddy is generated in a wake when a steering flow in the upper layer passes a seamount, induced by a surface cyclonic eddy. More observations suggest that the deep eddy should not be an episode in the area. Deep eddies significantly increase the velocity intensity and enhance the mixing in the deep ocean, also have potential implication for deep-sea sediments transport.


The 3D Genome as a Target for Anticancer Therapy.
The role of 3D genome organization in the precise regulation of gene expression is well established. Accordingly, the mechanistic connections between 3D genome alterations and disease development are becoming increasingly apparent. This opinion article provides a snapshot of our current understanding of the 3D genome alterations associated with cancers. We discuss potential connections of the 3D genome and cancer transcriptional addiction phenomenon as well as molecular mechanisms of action of 3D genome-disrupting drugs. Finally, we highlight issues and perspectives raised by the discovery of the first pharmaceutical strongly affecting 3D genome organization.


Angiogenic activity of classical hematopoietic cytokines.
Hematopoiesis is regulated by several cytokines with pleiotropic activity. Several evidences have clearly demonstrated that these molecules, formerly regarded as specific for the hematopoietic system, also affect certain endothelial cell functions and that hematopoietic factors clearly influence angiogenesis. This review article summarizes the most important literature data concerning this inconvertible relationship.


Efficacy and safety of selenium nanoparticles administered intraperitoneally for the prevention of growth of cancer cells in the peritoneal cavity.
Peritoneal implantation of cancer cells, particularly postoperative seeding metastasis, frequently occurs in patients with primary tumors in the stomach, colon, liver, and ovary. Peritoneal carcinomatosis is associated with poor prognosis. In this work, we evaluated the prophylactic effect of intraperitoneal administration of selenium (Se), an essential trace element and a putative chemopreventive agent, on peritoneal implantation of cancer cells. Elemental Se nanoparticles were injected into the abdominal cavity of mice, into which highly malignant H22 hepatocarcinoma cells had previously been inoculated. Se concentrations in the cancer cells and tissues, as well as the efficacy of proliferation inhibition and safety, were evaluated. Se was mainly concentrated in cancer cells compared to Se retention in normal tissues, showing at least an order of magnitude difference between the drug target cells (the H22 cells) and the well-recognized toxicity target of Se (the liver). Such a favorable selective distribution resulted in strong proliferation suppression without perceived host toxicity. The mechanism of action of the Se nanoparticle-triggered cytotoxicity was associated with Se-mediated production of reactive oxygen species, which impaired the glutathione and thioredoxin systems. Our results suggest that intraperitoneal administration of Se is a safe and effective means of preventing growth of cancer cells in the peritoneal cavity for the above-mentioned high-risk populations.


Osteoporosis knowledge, health beliefs, and self-efficacy in Hong Kong Chinese men.
A total of 277 Hong Kong Chinese men participated in this prospective cohort study. Their osteoporosis knowledge was average. Their perceived susceptibility to osteoporosis was low. Barriers to lifestyle modifications were the strongest predictor for self-efficacy in adopting these activities. These results are useful for planning osteoporosis public awareness campaigns for men. Male osteoporosis had long been neglected despite one-third of fractures occurring in men. Lifestyle modification through education is the main tactic in osteoporosis prevention, but current programs and strategies are designed for postmenopausal women. Understanding men's knowledge, health belief, and self-efficacy in adopting osteoporosis prevention strategies can help to design a specific program for men. A prospective cohort study was conducted in three men's health clinics in Hong Kong from September to October 2020, recruiting 277 men aged ≥ 20 years. They completed a questionnaire consisting of sociodemographic data, 14 general questions from the Facts on Osteoporosis Quiz (FOOQ), Male Osteoporosis Knowledge Quiz (MOKQ), Osteoporosis Health Belief Scale (OHBS), and Osteoporosis Self-Efficacy Scale (OSES). Scores from these scales and their association with sociodemographic data were reported. Correlations between age, knowledge, health beliefs, and self-efficacy were studied using the Health Belief Model. The mean age was 36.4 years old, and 52% had university education. Their mean FOOQ + MOKQ score was 10.8 out of 20; mean OHBS score was 129.2 out of 210; and mean OSE-Exercise and OSE-Calcium scores were 66.4 and 68.9 out of 100 respectively. Self-efficacy of exercise was correlated with young age, perceived exercise benefits, and little barriers to exercise (p < 0.01). Self-efficacy of calcium intake was positively correlated with health motivation and self-efficacy of exercise and negatively correlated with barriers to calcium intake (p < 0.01). Male osteoporosis awareness programs should focus on improving knowledge, enhancing awareness on susceptibility, promoting benefits of lifestyle modification, and helping men overcome perceived barriers.


Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in a case of recurrent carcinoma of the oral cavity.
Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation. The discussed underlying mechanism for this effect is an synergistic cytotoxic and radiosensitizing effect of hyperthermia. In addition, tumor blood-flow and, consequently, tumor oxygenation are increased during hyperthermia. Tumor response to irradiation and chemotherapy of well-oxygenated and vascularized tumors, in general, is superior to that of hypoxic tumors. Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors. Technically, the head-neck area remains outside the hyperthermia chamber during whole-body hyperthermia (WBH) as currently applied in a number of cancer treatment regimens. The aim of this therapeutic approach was to evaluate whether the blood flow during WBH also increased in the head-neck region and, if so, whether tumor oxygenation increase accordingly. A 60-year-old male Caucasian patient, with the original diagnosis of pT3 pN2b M0 squamous cell carcinoma of the oral cavity, who had undergone primary surgery and irradiation (total dose 60 Gy), developed three local recurrences with consecutive surgical resection, presenting now with another recurrent local tumor (histologically confirmed) without surgical or radiotherapeutical options due to lymphangiosis carcinomatosa. WBH was applied under full anaesthesia, using a humidified radiant heat device (Enthermics Medical Systems RHS-7500) in combination with synchronous application of chemotherapy (ifosfamide and carboplatin). Four cycles of this combined treatment (one cycle per month) were given. Tumor oxygenation and temperature were continuously monitored by Licox catheters by means of one point measurement during each treatment (3.5 h). With a latency of 10 min, the increase of intratumoral temperature in the oral cavity was comparable to reference values in the esophagous. Maximum intratumoral temperature (oral cavity) was 41.8 degrees C (F). The average increase of tumor oxygenation was more than 100% in each individual cycle. Clinically, a partial tumor response was observed. During combined WBH and polychemotherapy, oxygenation is also significantly improved in a tumor in the head and neck area despite the fact that head and neck area remains outside the hyperthermia chamber during WBH. Intratumoral temperatures achieved are comparable to esophageal and rectal temperatures obtained during WBH.


Vibration sensory thresholds depend on pressure of applied stimulus.
Vibration sensory thresholds (VSTs) were estimated in 40 healthy subjects and 8 with diabetic peripheral neuropathy. A vibrameter and a biothesiometer were used at four sites and at differing pressures. In normal subjects, with the vibrameter at 200 g, mean VST +/- SE for all sites was 1.87 micron +/- 0.22 and at 400 g dropped to 1.08 micron +/- 0.15 (P less than .0001). In 20 of these subjects with a biothesiometer at 200 and 400 g, mean VST fell from 12.8 +/- 1.5 to 11.1 +/- 1.1 (arbitrary units) (P = .01) when the greater pressure was applied. In the 8 subjects with peripheral neuropathy, with the vibrameter at 200 and 400 g, respectively, mean VST fell from 70.7 +/- 26 to 7.2 +/- 1.8. VST in these subjects was estimated again after 1 mo and showed strong correlations with the previous values. Biothesiometer results correlated with vibrameter results at all sites. Thus, VST decreases as the pressure of the applied stimulus is increased and this effect appears to be more marked in peripheral neuropathy. This has important consequences in monitoring this condition.


Development of a score that predicts survival among patients with bone metastasis revealing solid tumor.
Bone metastases revealing solid tumors require a multidisciplinary treatment that may include aggressive surgery. Nevertheless, decision making is very difficult because of lack of reliable guidance for life expectancy. Therefore, we had conducted a retrospective study to analyze prognostic factors in this vulnerable population. We reviewed the medical charts of 119 consecutive patients with solid tumors treated between August 1999 and December 2007. Survival was estimated using Kaplan-Meier method. Prognostic factors were assessed with Log-rank test and Cox model. There were 77 men and 42 women. The median age was 57 (range, 29-84). The most frequent primaries were lung (51 cases), unknown primary (42 cases), and breast (six cases). The median overall survival was 118 days (1-2,815). Six independent prognostic factors were identified by multivariate analysis: Karnosky index < 80% (HR = 1.92), albuminemia < 38 g/l (HR = 2.60), natremia < 135 mEq/l (HR = 2.78), platelet count > 500,000/mm(3) (HR = 2.71), cutaneous metastasis (HR = 4.6), and pleural metastasis (HR = 4.76). For example, patients with < or =2 of these prognostic factors experienced a median overall survival of 196 days (1-2,875) and their risk of death within the 90 days was 15/77. On the contrary, the patients with more than two poor prognostic factors experienced a median overall survival of about 80 days (1-834) and their risk of early death was 22/32. We had proposed an easily obtained at bedside score that needs further validation on independent cohort.


Type II endoleaks after endovascular repair of abdominal aortic aneurysm are not always a benign condition.
The aim of the study was to determine whether type II endoleak (T2E) after endovascular repair of abdominal aorta (EVAR) is a benign condition (ie, not associated with growth, reintervention, rupture, or death). Data from patients who underwent EVAR for atherosclerotic infrarenal aortic aneurysms between June 1995 and May 2010 in the Vascular Surgery Department of Henri Mondor Hospital were prospectively collected. Data from patients presenting with at least one T2E on computed tomography scan during their follow-up were compared with those with no T2E. Three subcategories of T2E were studied according to time of occurrence (early or late), persistence (persistent or transient), and recurrence (recurrent or not recurrent). Seven hundred patients were included with follow-up ranging from 1 month to 15 years (median, 31.3 months; range, 12.4-61.4); 201 (28.9%) had at least one T2E. Patients with T2Es were significantly older (P < .001), female (P = .015), had larger aneurysms (P = .019), and patent lumbar arteries (P = .003). Patients without T2Es had a higher incidence of current smoking (P < .001) and chronic obstructive pulmonary disease (P < .005). Multivariate analysis showed risk of T2E was increased in older patients (odds ratio [OR], 1.04; confidence interval [CI], 95% 1.02-1.06; P < .001) and in those with patent lumbar arteries (OR, 1.70; CI, 95% 1.16-2.50; P = .007), and was reduced in active smokers (OR, 0.16 CI, 95% 0.04-0.71; P = .015) or patients with coronary artery disease (OR, 0.65; CI, 95% 0.45-0.92; P = .016). Patients with T2Es had more complications (death, rupture, reintervention, or conversion) (P < .001) and greater aneurysm sac enlargement (>5 mm upon follow-up) (P < .001). Multivariate analysis showed T2E was a risk factor for aneurysm diameter growth >5 mm; this risk was increased if T2E persisted more than 6 months (hazard ratio [HR], 3.16; CI, 95% 2.55-6.03; P < .001), was recurrent (HR, 1.88; CI, 95% 1.18-3.01; P = .008), or associated with a type I or III endoleak (HR, 1.96; CI, 95% 1.41-2.73; P < .001). Recurrent T2E was associated with a higher rate of reintervention (P = .04) and conversion to open surgery (P = .028). Not all T2Es are benign. Recurrent as well as persistent T2Es are prone to life-threatening complications.


Interleukin 1 alpha stimulates nuclear phospholipase C in human osteosarcoma SaOS-2 cells.
Interleukin 1 (IL-1) is one of the most potent stimulators of bone resorption. However, the early biochemical events elicited by IL-1 receptor binding are not fully understood. Here we show that in human osteosarcoma SaOS-2 cells the treatment with IL-1 alpha is able to evoke a rapid and transient increase of nuclear phospholipase C (PLC) activity. A parallel decrease of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate is observed. All these events are strictly confined to the nuclear compartment without affecting the cytoplasmatic inositol lipid pool. In addition we show that by Western blot analysis with specific monoclonal antibodies the PLC gamma is located both in the cytoplasm and in the nucleus, while PLC beta appears exclusively localized in the nucleus. Moreover, the increase of PLC activity in response to IL-1 alpha is completely neutralized by monoclonal antibody against the beta-form. While confirming the existence of an autonomous nuclear phosphoinositide signaling system, our data clearly indicate that in SaOS-2 cells one of the earliest events following IL-1 alpha treatment is the breakdown of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate because of the activation of a specific nuclear PLC isoform.


Young women facing multiple and intersecting stressors of modernity, gender orders and youth.
This article aims to explore stressors experienced by Swedish adolescent girls and young women, specifically understood in relation to social context and gender theory. Interviews were conducted with 40 young Swedish women, aged 16-25 years, who had sought help at a youth health centre for stress problems. Using qualitative content analysis we identified three clusters of stressors: "the stressors of modernity", "the stressors of gendered orders", and "the stressors of youth". The results revealed that multiple and intersecting discourse-shaped stressors and demands connected to essential life spheres contribute not only to experiences of distress but also to feelings of constraint. Gendered individualism and healthism proved to be essential in understanding the young women's experienced stress. Failing social support from adults, gendered demands and responsibility taking were also illuminated. This calls for a broad contextualized and gender-sensitive approach to young women's stress and health problems.


A Golgi and electron microscopic study of a dysplastic gangliocytoma of the cerebellum.
The fine structure of a dysplastic gangliocytoma of the cerebellum is studied by means of the Golgi method and electron microscopic examination. Thick proximally unbranched dendrites with terminal arborizations and varicose inflorescences in the form of a basket are stained with the Golgi method. Axons are always descendant to the inner myelinated layer of the redistributed cerebellar cortex, while ascendant collaterals are observed at the level of the outer myelinated layer. Clear and dense-core vesicles and synapses are common in the cellular profiles under electron microscopic examination. From these data and because of the lack of putative connections through the white matter, an organized, self-regulated, catecholamine-mediated complex may be postulated.


Left atrial ablation versus biatrial ablation in the surgical treatment of atrial fibrillation.
The purpose of this study was to compare the clinical and rhythm outcomes between left atrial ablation and biatrial ablation in patients with atrial fibrillation-associated mitral valve diseases. Data were collected on 284 patients who underwent left atrial ablation (n = 85) or biatrial ablation (n = 199) of atrial fibrillation using a cryoablation system combined with mitral operation from 2006 through 2009. Outcomes were compared using a propensity score study design based on 20 baseline patient characteristics. In baseline characteristics, patients in the biatrial group were more likely to have higher risk clinical and echocardiographic profiles than patients in the left atrial group. There were 2 early deaths (0.7%), 1 in each group, and 5 cases of permanent pacemaker implantation (1.8%) only in the biatrial group. Follow-up was complete in 95.1% (n = 270). During a mean follow-up duration of 26.0 ± 13.3 months, there were 12 late deaths (1 in the left atrial group, 11 in the biatrial group). Cumulative incidence of atrial fibrillation in the absence of antiarrhythmic medications at 2 years was 25.9% ± 5.8% in the left atrial group and 14.3% ± 2.8% in the biatrial group (adjusted hazard ratio 3.06, 95% confidence interval: 1.41 to 6.66, p = 0.005). Major adverse events included stroke in 1, cardiac reoperation in 3, and anticoagulation-related hemorrhages in 16, infective endocarditis in 1, and mechanical valve thrombosis in 1, with no significant intergroup differences in major event-free survival rate (p = 0.73). Compared with left atrial ablation, biatrial ablation was more effective in restoration and maintenance of sinus rhythm without increasing the risk of postoperative complications.


Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting.
Despite the recent rise of RNA-seq datasets combining single-cell (sc) resolution with 4-thiouridine (4sU) labelling, analytical methods exploiting their power to dissect transcriptional bursting are lacking. Here, we present a mathematical model and Bayesian inference implementation to facilitate genome-wide joint parameter estimation and confidence quantification (R package: burstMCMC). We demonstrate that, unlike conventional scRNA-seq, 4sU scRNA-seq resolves temporal parameters and furthermore boosts inference of dimensionless parameters via a synergy between single-cell resolution and 4sU labelling. We apply our method to published 4sU scRNA-seq data and linked with ChIP-seq data, we uncover previously obscured associations between different parameters and histone modifications.


Resection of the Portal-Superior Mesenteric Vein in Pancreatic Cancer: Pathological Assessment and Recurrence Patterns.
The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.


Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study.
Alpha-2 adrenergic agonists clonidine and dexmedetomidine, are well known to produce analgesia through an opioid independent mechanism. Alpha-2 agonists are used as an adjuvant to local anesthetic agents to extend the duration of spinal, epidural and brachial plexus blocks. We compared clonidine and dexmedetomidine as an adjuvant to Ropivacaine in cervical epidural anesthesia (CEA) with respect to onset and duration of sensory block, duration of analgesia and adverse effects. A total 150 American Society of Anesthesiologists Class I or II adult female patients who were scheduled to undergo modified radical mastectomy were randomly allocated to the following two groups to receive CEA: Group D receive 15 mL of 0.375% ropivacaine combined with 1 μg/kg of dexmedetomidine; Group C received 15 mL of 0.375% ropivacaine combined with 1.5 μg/kg of clonidine. The onset of sensory block, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), sedation scores, and the incidences of adverse effects, such as hypotension, bradycardia, and oxygen desaturation were recorded. The addition of dexmedetomidine to ropivacaine (Group D) resulted in faster onset of sensory block time compared with the addition of clonidine to ropivacaine (Group C) (95% confidence interval [CI]: 14.53 ± 2.96 vs. 16.72 ± 4.43 P = 0.032). The duration of analgesia block in Group D was significantly longer than that in Group C (95% CI: 234.65 ± 23.76 vs. 286.76 ± 34.65; P = 0.037). The Ramsay sedation score at in Group D were significantly higher between 20 and 60 min as compared to Group C (P < 0.022). MAP level and HR level in Group D and Group C were comparable. The addition of dexmedetomidine to low dose ropivacaine for CEA could shorten the onset of sensory block and extend the duration of analgesia with optimum sedation without episodes of hypoxemia as compared to addition of clonidine to ropivacaine.


Stay Home, Drink at Home? A Daily Diary Study on College Students' Alcohol and Social Media Use during the COVID-19 Pandemic.
COVID-19 and measures to contain it may have impacted college students' behavior, including their drinking behavior. Students' drinking may have decreased-for example, due to the closure of bars-but problematic drinking may have increased-for example, due to (solitary) drinking at home. Another behavior that has increased due to COVID-19 and the accompanying social isolation is students' social networking site (SNS) use. This is worrisome because students' SNS use has been shown to increase their alcohol use. Nevertheless, little research has investigated these behaviors and the possible link between them during a lockdown. Therefore, this study aimed to examine (1) whether students engaged in drinking during a lockdown, (2) whether they displayed their drinking behavior on SNSs, and (3) whether exposure to and posting of alcohol-related content was linked to their daily alcohol use. 337 college students (Mage = 20.63 years, SDage = 1.55 years; 50.3% male) participated in a two-week daily diary study. Descriptive statistical analyses and generalized linear mixed modeling (GLMM) were deployed. Descriptive analysis results showed that during the week, students' drinking occurred with friends in dormitories, while in the weekend, this behavior shifted to drinking with friends and parents at home. Moreover, students mostly saw visual and posted textual posts of this drinking on SNSs. Furthermore, GLMM revealed associations between exposure to alcohol postings, sharing of alcohol postings, and students' probability of drinking on the same day. This study provides important insights into students' alcohol use and its underlying mechanisms during health crises.


Benthic recovery after fish farming cessation: a "beyond-BACI" approach.
The development of a benthic environment after fish-farming cessation was examined. To ascertain whether recovery occurred, several abiotic (granulometry, acid-volatile sulfides, total phosphorus and redox potential) and biotic (polychaete abundance) variables were monitored using a "beyond-BACI" approach. Before the cessation of farming, the geochemical conditions and polychaete assemblages differed among the impacted and control sites. After cessation, an improvement of the geochemical conditions was achieved. A significant tendency toward a recovery of the polychaete assemblage in the impacted area was observed, but significant differences still remained compared with the control sites. The acid-volatile sulfide level was responsible for these differences. The abundance of polychaete families associated with organically enriched sediments diminished at the impacted site after cessation, whereas the abundance of some sensitive and omnivorous families increased. The "beyond-BACI" approach provided a wider framework than other approaches, enabling us to differentiate the natural variability from those changes induced by the fish farm and farming cessation.


Nonintubated-Awake Anesthesia for Uniportal Video-Assisted Thoracic Surgery Procedures.
Nonintubated video-assisted thoracic surgery (VATS) strategies are gaining popularity. This review focuses on noninutbated VATS, and discusses advantages, indications, anesthetic techniques, and approaches to intraoperative crisis management. Advances in endoscopic, endovascular, and robotic techniques have expanded the range of surgical procedures that can be performed in a minimally invasive fashion. The nonintubated thoracoscopic approach has been adapted for use with major lung resections. The need for general anesthesia and endotracheal intubation has been reexamined, such that regional or epidural analgesia may be sufficient for cases where lung collapse can be accomplished with spontaneous ventilation and an open hemithorax.


Gene expression identifies heterogeneity of metastatic propensity in high-grade soft tissue sarcomas.
Metastatic propensity of soft tissue sarcoma (STS) is heterogeneous and may be determined by gene expression patterns that do not correlate well with morphology. The authors have reported gene expression patterns that distinguish 2 broad classes of clear cell renal carcinoma (ccRCC-gene set), and other patterns that can distinguish heterogeneity of serous ovarian carcinoma (OVCA-gene set) and aggressive fibromatosis (AF-gene set); however, clinical follow-up data were not available for these samples. In the current study, gene expression patterns in 73 samples of high-grade STS were examined using spotted cDNA microarray slides that contained ∼16,000 unique UniGene clusters. Approximately 50% of the genes present in the ccRCC-, OVCA-, and AF-gene sets were also represented in the data from this chip set, and these were combined to form a composite gene set of 278 probes. Hierarchical clustering using this composite gene set suggested the existence of subsets of the STS samples. Analysis revealed differences in the time to development of metastatic disease between the clusters defined by the first branch point of the clustering dendrogram (P = .005), and also among the 4 different clusters defined by the second branch points (P = .001). This approach suggests the existence of >2 subsets of high-grade pleomorphic STS, each with distinct clinical behavior. A composite gene set such as that described here may be useful to stratify STS in clinical trials, and may be of practical utility in patient management.


Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell.
Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.


Association between fine particulate matter and atrial fibrillation in implantable cardioverter defibrillator patients: a systematic review and meta-analysis.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with several risk factors. Recent studies have suggested that the exposure to fine particulate matter (PM2.5) increased the incidence of AF, but there is no meta-analysis of AF occurrence due to the exposure to PM2.5 in implantable cardioverter defibrillator (ICD) patients. We conducted a systematic review of publication using PubMed, Embase, the Cochrane library, and Web of Science to explore the association between PM2.5 and AF within ICD patients. The chosen studies were published until June 11, 2020. The I2 statistic and Q test were used to examine statistical heterogeneity across studies. Further sensitivity analyses were carried out to ascertain the reason for heterogeneity. Fixed or random-effect model was used to combine the effects. Final result was presented as the OR with 95% CI of increased incidence of AF for every 10 μg/m3 PM2.5 concentration increased. After screening our analysis contained four studies and involved 1689 AF events from 572 patients. After using the random-effect model to combine the included study result, the overall OR was 1.24 (95% CI 1.00-1.53). Our meta-analysis indicated that PM2.5 exposure had an adverse effect on AF incidence in ICD patients.


Short-term modulation of the renin-angiotensin system does not alter plasma adrenomedullin concentration in humans.
Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are novel hypotensive peptides produced from the same precursor. A relationship between AM and the renin-angiotensin-aldosterone (RAA) axis was reported in several studies, but the response of the above two peptides to short-term modulation of the RAA axis in humans is not yet clear. Here, we assessed the responses of AM and PAMP in patients with varying RAA system status, including renovascular hypertension (RVH) and primary aldosteronism (PA). Essential hypertension (EHT), RVH and PA patients were hospitalized and maintained on a standard diet (NaCl 10 g/day). The patients underwent a captopril (25 mg) loading test. A renin-secretion stimulating test (furosemide 1 mg/kg, i.v. +2 h of walking) and an ACTH loading test were performed for the PA patients. The plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma AM and PAMP levels were monitored before and after the loadings. In the basal state, significantly higher concentrations of AM and PAMP were shown in the RVH patients compared to the other groups. AM and PAMP were significantly correlated with PRA but not PAC in all patients. The AM and PAMP levels were not affected by the captopril loading with or without a hypotensive reaction. The AM and PAMP levels were increased only slightly despite the large increase in PAC induced in the PA patients by the renin-secretion stimulating and ACTH loading tests. The responses of plasma AM and PAMP to a short-term modulation of the RAA system were relatively small, despite the correlations observed between PRA and AM or PAMP.


Dietary L-serine confers a competitive fitness advantage to Enterobacteriaceae in the inflamed gut.
Metabolic reprogramming is associated with the adaptation of host cells to the disease environment, such as inflammation and cancer. However, little is known about microbial metabolic reprogramming or the role it plays in regulating the fitness of commensal and pathogenic bacteria in the gut. Here, we report that intestinal inflammation reprograms the metabolic pathways of Enterobacteriaceae, such as Escherichia coli LF82, in the gut to adapt to the inflammatory environment. We found that E. coli LF82 shifts its metabolism to catabolize L-serine in the inflamed gut in order to maximize its growth potential. However, L-serine catabolism has a minimal effect on its fitness in the healthy gut. In fact, the absence of genes involved in L-serine utilization reduces the competitive fitness of E. coli LF82 and Citrobacter rodentium only during inflammation. The concentration of luminal L-serine is largely dependent on dietary intake. Accordingly, withholding amino acids from the diet markedly reduces their availability in the gut lumen. Hence, inflammation-induced blooms of E. coli LF82 are significantly blunted when amino acids-particularly L-serine-are removed from the diet. Thus, the ability to catabolize L-serine increases bacterial fitness and provides Enterobacteriaceae with a growth advantage against competitors in the inflamed gut.


[A decrease in the level of unscheduled DNA synthesis in preparations of irradiated rat hepatocyte nuclei under the effect of polyamines].
The results obtained show the possibility of polyamine (spermine and spermidine) utilization to stabilize the nuclear chromatin and to protect it against nuclease degradation in the course of isolation of liver cell nuclei. Besides, the inhibition of the unscheduled DNA synthesis induced by nuclease incision and by gamma- or UV-radiation was demonstrated in the presence of polyamines.


Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that arises from lack of expression of paternally inherited genes known to be imprinted and located in the chromosome 15q11-q13 region. PWS is considered the most common syndromal cause of life-threatening obesity and is estimated at 1 in 10,000 to 20,000 individuals. A de novo paternally derived chromosome 15q11-q13 deletion is the cause of PWS in about 70% of cases, and maternal disomy 15 accounts for about 25% of cases. The remaining cases of PWS result either from genomic imprinting defects (microdeletions or epimutations) of the imprinting centre in the 15q11-q13 region or from chromosome 15 translocations. Here, we describe the clinical presentation of PWS, review the current understanding of causative cytogenetic and molecular genetic mechanisms, and discuss future directions for research.


[Effect of glucagon and hydrocortisone on aldolase turnover in the rat liver after total x-irradiation].
A study was made of the effect of glucagon and hydrocortisone on aldolase metabolism in rat liver after total-body X-irradiation. The hormonal regulation of the enzyme metabolism in the exposed rats was shown to vary from that of intact animals.


Plasmodium falciparum and Plasmodium chabaudi: characterization of glycosylphosphatidylinositol-degrading activities.
Merozoites of malaria parasites have a membrane-bound serine protease whose solubilization and subsequent activity depend on a parasite-derived glycosylphosphatidylinositol-phospholipase C (GPI-PLC). The GPI-degrading activities from both Plasmodium falciparum and Plasmodium chabaudi have been characterized and partially purified by phenylboronate chromatography. They are membrane-bound, developmentally regulated, calcium-independent enzymes and as such they resemble GPI-PLC of Trypanosoma brucei. Furthermore, a T. brucei GPI-PLC-specific monoclonal antibody (mAT3) immunoprecipitates the plasmodial GPI-degrading activity. Thin-layer chromatography is suggestive of two activities: a GPI-PLC and a phospholipase A.


Environmentally friendly power generator based on moving liquid dielectric and double layer effect.
An electrostatic power generator converts mechanical energy to electrical energy by utilising the principle of variable capacitance. This change in capacitance is usually achieved by varying the gap or overlap between two parallel metallic plates. This paper proposes a novel electrostatic micro power generator where the change in capacitance is achieved by the movement of an aqueous solution of NaCl. A significant change in capacitance is achieved due to the higher than air dielectric constant of water and the Helmholtz double layer capacitor formed by ion separation at the electrode interfaces. The proposed device has significant advantages over traditional electrostatic devices which include low bias voltage and low mechanical frequency of operation. This is critical if the proposed device is to have utility in harvesting power from the environment. A figure of merit exceeding 10000(10(8)μW)/(mm(2)HzV(2)) which is two orders of magnitude greater than previous devices, is demonstrated for a prototype operating at a bias voltage of 1.2 V and a droplet frequency of 6 Hz. Concepts are presented for large scale power harvesting.