Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.
The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS-/- mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS-/- mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS-/- mice and their wild type controls received alcohol (0.0, 2.2, or 4.4mg/g) daily over postnatal days 4-9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS-/- and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS-/- mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS-/- mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS-/- mice, but not in wild type. Thus, homozygous mutation of the nNOS gene increases vulnerability to alcohol-induced cerebellar dysfunction and neuronal loss. nNOS is the first gene identified whose mutation worsens alcohol-induced cerebellar behavioral deficits.


Quality of life in children with OCD before and after treatment.
Quality of life (QoL) is a well-established outcome measure. In contrast to adult obsessive-compulsive disorder (OCD), little is known about the effects of treatment on QoL in children with OCD. This study aimed to assess QoL after cognitive behavioural therapy (CBT) in children and adolescents with OCD compared with the general population and to explore factors associated with potential changes in QoL after treatment. QoL was assessed in 135 children and adolescents (ages 7-17; mean 13 [SD 2.7] years; 48.1% female) before and after 14 CBT sessions, using self-report and a caregivers proxy report of the Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R). QoL was compared with an age- and gender-matched sample from the general population. Before treatment, QoL was markedly lower in children with OCD compared with the general population. QoL improved significantly in CBT responders (mean score change 7.4), to the same range as QoL in the general population. Non-responders reported no QoL changes after treatment, except for one patient. Comorbidity, family accommodation and psychosocial functioning were not associated with changes in QoL after treatment. To our knowledge, this is the first study of the changes in QoL after treatment of paediatric OCD. The assessment of QoL beyond symptoms and function in children with OCD has been shown to be reliable and informative. The results of this study support the application of QoL assessment as an additional measure of treatment outcome in children and adolescents with OCD.


Uptake of fluorescence-labeled dextrans by 10T 1/2 fibroblasts following permeation by rectangular and exponential-decay electric field pulses.
The uptake of fluorescence-labeled dextrans by adherent 10T 1/2 murine fibroblasts following electric field pulse application was used as a criterion for the efficiency of electropermeation. The cells in monolayers were permeated by immersing a coaxial electrode in culture dishes. The percentage of cells which exhibited fluorescence uptake following electric field pulse application was measured at independently varying pulse field strength and pulse length. Dextrans with molecular weights equal to or higher than 41,000 dalton require higher field strength or longer pulse time to penetrate the cells. There is no detectable advantage of using a rectangular pulse against using an exponential decay pulse of similar power. The uptake was proportional to the product of the pulse amplitude and duration over the experimental range of 40-950 microseconds and 0.1-14.5 kV/cm. Cell survival decreases at the upper end of this range. The result provides a direct comparison of electric parameters which so far have not been standardized with regard to cell electropermeation.


[Effect of platelet reactivity on clinical events in patients using bivalirudin in selective percutaneous coronary intervention].
Objective: To investigate the effect of platelet reactivity and other clinical factors on the postoperative 1-year adverse clinical events in patients who underwent selective percutaneous coronary intervention (PCI) anticoagulated with bivalirudin. Methods: This is a multicenter, retrospective and observational study, enrolling 632 patients at high risk of bleeding adjudicated by operators who underwent selective PCI anticoagulated with bivalirudin and had preoperative thrombelastography (TEG) test results in Fuwai Hospital, Northern Theater General Hospital and Xinxiang Central Hospital between January 2017 and August 2018. Platelet reactivity was tested by TEG and adenosine-induced maximal amplitude (MAADP) was recorded. According to MAADP patients were divided into three groups: low on-treatment platelet reactivity (LTPR) group (MAADP<31 mm, n=229), normal on-treatment platelet reactivity (NTPR) group (31 mm≤MAADP≤47 mm, n=207) and high on-treatment platelet reactivity (HTPR) group (MAADP>47 mm, n=196). The endpoints consisted of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events. The definition of MACCE was the composite of all-cause mortality, myocardial infarction, intrastent thrombosis, stroke and revascularization. Bleeding events were defined by bleeding academic research consortium (BARC) type 2, 3 and 5 bleeding. Using multivariate Cox regression to analyze the factors of MACCE and bleeding events in patients underwent selective PCI anticoagulated with bivalirudin. Results: A total of 632 patients were finally enrolled in the study with age of (68.3±10.0) years and there were 423 (66.9%) males. All of 632 patients finished one-year follow-up, and 48 (7.6%) patients occurred MACCE and 11 (1.7%) patients occurred bleeding events. There was not statistically significant difference in the incidence of MACCE (8.3% (19/229) vs. 6.3% (13/207) vs.8.2% (16/196), P=0.68) and bleeding events (1.8% (4/229) vs. 2.9% (6/207) vs. 0.5% (1/196), P=0.17) in LTPR, NTPR and HTPR group. Multivariate Cox regression showed that HTPR was not the independent factor of MACCE (HR=1.25, 95%CI 0.67-2.30, P=0.49), and the history of peripheral vessel disease was the independent risk factor of MACCE (HR=2.47, 95%CI 1.19-5.11, P=0.02). LTPR was not the independent factor of bleeding events (HR=1.35, 95%CI 0.39-4.66, P=0.64), and the independent factors of bleeding events were history of peripheral vessel disease (HR=3.95, 95%CI 1.03-15.22, P=0.05) and hemoglobin (HR=0.96, 95%CI 0.93-0.99, P=0.01). Conclusions: In patients undergoing selective PCI anticoagulated with bivalirudin, there is no significant association between platelet reactivity and postoperative 1-year MACCE or bleeding events. History of peripheral vessel disease is an independent risk factor of MACCE, and history of peripheral vessel disease and decreased hemoglobin are independent risk factors of bleeding events.


Surviving mothers and lost babies - burden of stillbirths and neonatal deaths among women with maternal near miss in eastern Ethiopia: a prospective cohort study.
Although maternal near miss (MNM) is often considered a 'great save' because the woman survived life-threatening complications, these complications may have resulted in loss of a child or severe neonatal morbidity. The objective of this study was to assess proportion of perinatal mortality (stillbirths and early neonatal deaths) in a cohort of women with MNM in eastern Ethiopia. In addition, we compared perinatal outcomes among women who fulfilled the World Health Organization (WHO) and the sub-Saharan African (SSA) MNM criteria. In a prospective cohort design, women with potentially life-threatening conditions (PLTC) (severe postpartum hemorrhage, severe pre-(eclampsia), sepsis/severe systemic infection, and ruptured uterus) were identified every day from January 1st, 2016, to April 30th, 2017, and followed until discharge in the two main hospitals in Harar, Ethiopia. Maternal and perinatal outcomes were collected using both sets of criteria. Numbers and proportions of stillbirths and early neonatal deaths were computed and compared. Of 1054 women admitted with PTLC during the study period, 594 women fulfilled any of the MNM criteria. After excluding near misses related to abortion, ectopic pregnancy or among undelivered women, 465 women were included, in whom 149 (32%) perinatal deaths occurred: 132 (88.6%) stillbirths and 17 (11.4%) early neonatal deaths. In absolute numbers, the SSA criteria picked up more perinatal deaths compared to the WHO criteria, but the proportion of perinatal deaths was lower in SSA group compared to the WHO (149/465, 32% vs 62/100, 62%). Perinatal mortality was more likely among near misses with antepartum hemorrhage (adjusted odds ratio (aOR) = 4.81; 95% CI = 1.76-13.20), grand multiparous women (aOR = 4.31; 95% confidence interval CI = 1.23-15.25), and women fulfilling any of the WHO near miss criteria (aOR = 4.89; 95% CI = 2.17-10.99). WHO MNM criteria pick up fewer perinatal deaths, although perinatal mortality occurred in a larger proportion of women fulfilling the WHO MNM criteria compared to the SSA MNM criteria. As women with MNM have increased risk of perinatal deaths (in both definitions), a holistic care addressing the needs of the mother and baby should be considered in management of women with MNM.


Modified habitats influence kelp epibiota via direct and indirect effects.
Addition of man-made structures alters abiotic and biotic characteristics of natural habitats, which can influence abundances of biota directly and/or indirectly, by altering the ecology of competitors or predators. Marine epibiota in modified habitats were used to test hypotheses to distinguish between direct and indirect processes. In Sydney Harbour, kelps on pier-pilings supported greater covers of bryozoans, particularly of the non-indigenous species Membranipora membranacea, than found on natural reefs. Pilings influenced these patterns and processes directly due to the provision of shade and indirectly by altering abundances of sea-urchins which, in turn, affected covers of bryozoans. Indirect effects were more important than direct effects. This indicates that artificial structures affect organisms living on secondary substrata in complex ways, altering the biodiversity and indirectly affecting abundances of epibiota. Understanding how these components of habitats affect ecological processes is necessary to allow sensible prediction of the effects of modifying habitats on the ecology of organisms.


GSK-3 Inhibition Modulates Metalloproteases in a Model of Lung Inflammation and Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is mainly characterized by aberrant extracellular matrix deposition, consequent to epithelial lung injury and myofibroblast activation, and inflammatory response. Glycogen synthase kinase 3 (GSK-3) is a serine-threonine kinase involved in several pathways, and its inhibition has been already suggested as a therapeutic strategy for IPF patients. There is evidence that GSK-3 is able to induce matrix metalloproteinase (MMP) expression and that its inhibition modulates MMP expression in the tissues. The aim of our study was to investigate the role of GSK-3 and its inhibition in the modulation of MMP-9 and -2 in an in vivo mouse model of lung fibrosis and in vitro using different cell lines exposed to pro-inflammatory or pro-fibrotic stimuli. We found that GSK-3 inhibition down-modulates gene expression and protein levels of MMP-9, MMP-2, and their inhibitors TIMP-1 and TIMP-2 in inflammatory cells harvested from bronchoalveolar lavage fluid (BALF) of mice treated with bleomycin as well as in interstitial alveolar macrophages and cuboidalized epithelial alveolar cells. To the same extent, GSK-3 inhibition blunted the increased MMP-9 and MMP-2 activity induced by pro-fibrotic stimuli in a human lung fibroblast cell line. Moreover, the αSMA protein level, a marker of fibroblast-to-myofibroblast transition involved in fibrosis, was decreased in primary fibroblasts treated with TGFβ following GSK-3 inhibition. Our results confirm the implication of GSK-3 in lung inflammation and fibrosis, suggesting that it might play its role by modulating MMP expression and activity but also pushing fibroblasts toward a myofibroblast phenotype and therefore enhancing extracellular matrix deposition. Thus, its inhibition could represent a possible therapeutic strategy.


[Pseudotumor focal xanthogranulomatous pyelonephritis in adults. Role of imaging technics in the diagnosis].
Based on 8 personal cases, pseudo-tumoral xanthogranulomatous pyelonephritis is reviewed with emphasis on diagnosis. The condition is a particular form of chronic renal suppuration of histologic definition (combined lesions of chronic pyelonephritis and xanthogranulomatous foam cells). Two forms are recognized: one diffuse, fairly frequent form corresponding to a pyonephrosis, and a pseudo tumoral focal form, the only type discussed in this report, which raises the problem of diagnosis of a renal mass that requires the application of all currently available exploration means to define its true nature. Intravenous urography, ultrasound and CT scan imaging show a non-specific mass of variable character. Selective renal arteriography sometimes shows inflammatory type vascularization, a valuable aid but again non-specific. Puncture biopsy has been used by few authors. However, the presence of a renal mass associated with a chronic pyelonephritis, lithiasis and recurrent episodes of urinary infection should suggest the diagnosis and make use of imaging techniques to detect the affection and adapt therapy, major oncologic surgery being of no utility. Perhaps NMR imaging will provide a step forward in tissue characterization, but it is too early to say.


Dendrimer grafts for delivery of 5-fluorouracil.
Polyamidoamine (PAMAM) dendrimers were prepared by linking methyl methacrylate and ethylenediamine successively on an amine core. Surface modification of PAMAM dendrimer was done by fatty acid grafting converting them to a unimolecular micellar system (Dendrimer grafts). IR, 1H NMR, 13C NMR studies confirmed the structure. The drug 5-fluorouracil (5-FU) was entrapped in dendrimer grafts. The effects of various solvents (ethanol, dichloromethane, tetrahydrofuran), pH and ionic strength on solubilization of 5-FU were determined. Phospholipid was further coated on the dendrimer grafts. The product was lyophilized and obtained as yellowish-white powder. Average particle size was ca. 375 nm as determined by Malvern's Mastersizer 4. Drug loading was ca. 53% by weight. Stability studies were conducted for 1 month at room temperature and 40 degrees C, where the systems were relatively stable. Release rate was sustained across cellulose tubing in PBS. In vivo studies were performed in albino rats and pharmacokinetic parameters and bioavailability were determined from the plasma profile of 5-FU. The phospholipid coated dendrimer graft formulation was found to be more effective orally than free drug. The lymphatic uptake was also increased indicating absorption of the developed formulation through the lymphatic route.


[A phase I study of intraperitoneal plus intravenous paclitaxel against gastric cancer with peritoneal dissemination (HGCG 0301)].
The safety of the intraperitoneal (ip) plus intravenous (iv) paclitaxel against gastric cancer with peritoneal dissemination was evaluated on a phase I dose escalation trial. Patients were treated with ip paclitaxel administered in 500 ml of normal saline before closing the abdomen, using the following dose levels: level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); and level 4, 80 mg/m(2), followed by iv infusion of the same doses of paclitaxel on days 14 and 21. Twelve patients were enrolled in this study: 7 underwent reduction surgery,while 5 had only a laparotomy. ip therapy was well tolerated, and did not bring about any postoperative complications even in patients who underwent gastrectomy. Although multiple NCI/CTC grade 1 toxicities and grade 2 anemia (4 of six patients at dose levels 2 and 3) were observed, there was no dose-limiting toxicity. The overall median survival time was 316 days, and that for patients who underwent gastrectomy was 413 days. Paclitaxel at a dose of 80 mg/m(2) can be delivered by the operative ip route with acceptable toxicity profile.


Inflammasome as a Therapeutic Target for Cancer Prevention and Treatment.
Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli. A primed inflammasome recruits adaptor proteins, activates CASP1 to enhance the proteolytic cleavage of pro-IL-1β and IL-18, and sends the signal to respond to each insult. Depending on stimuli and cell contexts, several inflammasomes are closely associated with the initiation and promotion of carcinogenesis. In contrast, inflammasomes also show an ambivalent effect on carcinogenesis by enhancing inflammatory cell death (pyroptosis) and repairing damaged tissues. Although the inflammasome plays a controversial role in carcinogenesis, it may be a promising target for human cancer prevention and treatment. A more in-depth study on the role of the inflammasome in carcinogenesis, based on stimuli, cell contexts, and cancer stages, can lead to the development of novel therapeutic strategies against malignant human cancers.


[Stress echocardiography: development and significance].
Exercise electrocardiography is still the primary method used in the non-invasive assessment of coronary artery disease. Stress echocardiography is now being increasingly used as a more sensitive adjunct technique to assess ischemia. Ischemia provoked by stress can induce reversible wall motion abnormalities which are disclosed by cross-sectional 2-dimensional echocardiography and standard projections. The types of stress used are physical exercise (bicycle, treadmill), atrial pacing or pharmacologic stimulation. In the latter, the catecholamine dobutamine has emerged as preferable to the vasodilators dipyridamole and adenosine. The diagnostic accuracy of dobutamine stress echocardiography is comparable to that of bicycle or treadmill exercise echocardiography, but dobutamine stress echocardiography is technically simpler and can be performed in patients unable to exercise. Its sensitivity in diagnosing ischemic or viable myocardium is comparable to that of nuclear methods, MRI or PET. In contrast to nuclear methods, stress echocardiography is however free of radiation. In the assessment of patients with coronary artery disease, stress echocardiography has been shown to be valuable for diagnosis, preoperative risk stratification and determination of prognosis. Furthermore, low dose dobutamine echocardiography can be used to detect viable myocardium. Despite these very promising aspects of the method, there are recognized disadvantages and limitations: stress echocardiography is very time-consuming and operator-dependent; its sensitivity correlates strongly with the number of studies performed; analysis of wall motion is performed qualitatively on a purely subjective level, and hence lacks the objectivity of a quantitative approach. These factors emphasize the need for intensive research to render stress echocardiographic analysis more objective. Automatic boundary detection of left ventricular endocardium, color-Doppler-based tissue imaging and three-dimensional reconstruction offer interesting perspectives in rendering the subjective more objective.


Carotenoid intake and asthma prevalence in Thai children.
Several antioxidant nutrients have been described to inversely correlate with asthma. In order to quantify the intake of these substances, it is possible to measure skin levels by Raman spectroscopy, a novel non-invasive technique that can also be used in children. This cross-sectional school-based study involved 423 children from a rural area of Thailand. Asthmatic children were diagnosed according to a Health Interview for Asthma Control questionnaire. Skin carotenoid levels were measured with Raman spectroscopy. Demographic data were obtained by directly interviewing children and their parents, whereas anthropometric parameters were measured by trained staff. Intake of carotenoids, vitamin A and C were evaluated by a food frequency questionnaire. Overall incidence of asthma in Thai schoolchildren (aged 3.5-17.8 years) was 17.3%. There was no significant difference in dietary intake of carotenoids and vitamin A and C, and skin carotenoid level between asthmatic and non-asthmatic children. Skin carotenoid level significantly correlated with all carotenoids and vitamin A intake (P<0.05). Carotenoids and vitamin A and C intakes, and skin carotenoid levels were not associated with the risk of asthma in Thai children. Skin carotenoids correlated with all carotenoids and vitamin A intake in mild to moderate degrees. Raman spectroscopy was confirmed to be a useful tool to determine antioxidant skin levels.


Efficacy generated by afatinib in a lung adenocarcinoma patient harboring HER2 S310Y mutation.
Afatinib exhibits therapeutic efficacy for lung adenocarcinoma patients harboring HER2 exon 20 insertions. HER2 S310Y single site substitution was discovered in recent years and afatinib efficacy for adenocarcinoma patients harboring S310Y mutation has not been reported. We presented a case of a 41-year-old male patient with lung adenocarcinoma harboring the HER2 S310Y mutation obtained clinical response to the treatment of afatinib, an oral HER family blocker. After the treatment of afatinib, the patient achieved partial response (PR) in chest lesions and almost complete response (CR) in intracranial lesions. He experienced progressive disease (PD) with liver metastasis and achieved a progression-free survival (PFS) of 5 months. He continually treated with afatinib after CT guided percutaneous radiofrequency ablation to eradicate the hepatic tumor cells and achieved stable disease (SD). In this study, we reported the first clinical evidence of efficacy generated by afatinib, the irreversible HER family inhibitor, targeting HER2 S310Y single site mutation in lung adenocarcinoma.


Triplets in extended nematic liquid crystals and polarons in their blends.
Photoinduced absorption shows that triplets are the primary photoexcited species in a series of conjugated liquid crystals containing thiophene and fluorene groups. We find that the triplet generation rate can be varied substantially by molecular design. The introduction of extra thiophene groups into the elongated molecules changes the intersystem crossing rate by over two orders of magnitude, while modifying the singlet and triplet energies by only small amounts. This result is attributed to the high spin-orbit coupling constant of sulfur: An increase in the number of sulfur atoms increases the spin-orbit coupling between the singlet and triplet states. These results are relevant to the design of organic light emitting diodes, lasers, and other devices where triplet formation has a major impact on device performance. The molecules are shown to act as effective electron donors when blended with a perylene molecule which acts as an electron acceptor. The electron transfer rate is faster than the singlet lifetime so that the blend shows the efficient charge separation required for a photovoltaic device.


Evaluating the implementation and use of a computerized physician order entry system: a case study.
A study at the urology clinic, Frederiksberg Hospital Denmark, the clinicians working procedures, when prescribing, dispensing and administrating drugs using a computerized physician order entry system (CPOE) showed an overwhelming majority of the clinicians who believed it does support the patient safety and quality of treatment despite the CPOE was not used to the expected degre.


Nanoliter-Scale Oil-Air-Droplet Chip-Based Single Cell Proteomic Analysis.
Single cell proteomic analysis provides crucial information on cellular heterogeneity in biological systems. Herein, we describe a nanoliter-scale oil-air-droplet (OAD) chip for achieving multistep complex sample pretreatment and injection for single cell proteomic analysis in the shotgun mode. By using miniaturized stationary droplet microreaction and manipulation techniques, our system allows all sample pretreatment and injection procedures to be performed in a nanoliter-scale droplet with minimum sample loss and a high sample injection efficiency (>99%), thus substantially increasing the analytical sensitivity for single cell samples. We applied the present system in the proteomic analysis of 100 ± 10, 50 ± 5, 10, and 1 HeLa cell(s), and protein IDs of 1360, 612, 192, and 51 were identified, respectively. The OAD chip-based system was further applied in single mouse oocyte analysis, with 355 protein IDs identified at the single oocyte level, which demonstrated its special advantages of high enrichment of sequence coverage, hydrophobic proteins, and enzymatic digestion efficiency over the traditional in-tube system.


Development of a novel aspherical mirror bender for an active grating.
A novel monolithic mechanical bender has been designed and fabricated to meet the requirements of an active polynomial grating in a new soft X-ray scattering and emission beamline at the National Synchrotron Radiation Research Center, Taiwan. This compact bender achieves nearly fixed center point under different bending conditions. Moreover, the compact bender can be bent to a desirable third-order polynomial surface profile to cancel the defocus and coma aberrations using two PZT actuators. Theoretical analysis reveals that the grating has unprecedented spectral resolving power. A detailed mechanical analysis has been conducted and a prototype bender was fabricated and tested. The results indicate that the performance of the bender is excellent and is therefore suitable to be used in the active grating.


Full superconducting dome of strong Ising protection in gated monolayer WS2.
Many recent studies show that superconductivity not only exists in atomically thin monolayers but can exhibit enhanced properties such as a higher transition temperature and a stronger critical field. Nevertheless, besides being unstable in air, the weak tunability in these intrinsically metallic monolayers has limited the exploration of monolayer superconductivity, hindering their potential in electronic applications (e.g., superconductor-semiconductor hybrid devices). Here we show that using field effect gating, we can induce superconductivity in monolayer WS2 grown by chemical vapor deposition, a typical ambient-stable semiconducting transition metal dichalcogenide (TMD), and we are able to access a complete set of competing electronic phases over an unprecedented doping range from band insulator, superconductor, to a reentrant insulator at high doping. Throughout the superconducting dome, the Cooper pair spin is pinned by a strong internal spin-orbit interaction, making this material arguably the most resilient superconductor in the external magnetic field. The reentrant insulating state at positive high gating voltages is attributed to localization induced by the characteristically weak screening of the monolayer, providing insight into many dome-like superconducting phases observed in field-induced quasi-2D superconductors.


Blood-brain interfaces in vertebrates: a comparative approach.
The neuronal microenvironment in the vertebrate brain is isolated from plasma by a series of selective membranes, including the blood-brain barrier, the choroid plexus, and the meningeal barrier. This review deals with the structure and function of these selective membranes in the different vertebrate classes. Present knowledge indicates that all vertebrates have brain barrier membranes and, further, that functional characteristics of these membranes are basically similar in all the vertebrate classes. The blood-brain barrier (or capillary-glial complex) and the meningeal barrier have many of the properties of a tight epithelium, including the presence of tight junctions and specific transport mechanisms. The choroidal epithelium is a typical secretory epithelium. The functional significance of the specialized membranes located at the blood-brain interface is considered, and we suggest that the phylogenetic development of a blood-brain barrier provided neurons of the vertebrate brain with a unique extracellular milieu optimal both for synaptic communication and for nonsynaptic communication via the entire extracellular space.


Implantable left ventricular assist devices.
The first bridge to transplant with a left ventricular assist device (LVAD) was preformed over 20 years ago. Since that time, the devices have continued to evolve and now patients are being supported with devices as an alternative to transplantation. The primary indication of end-stage heart failure remains the same but increased knowledge about patient selection, the timing of implant, and patient management have contributed to improved outcomes with decreasing adverse events. Multiorgan failure, right ventricular failure, bleeding, infection, thromboembolism, and device malfunction continue to be the most serious threats to long-term survival in these patients. Despite that, patients who do well are now able to be discharged from the hospital and resume relatively normal lives with the devices. The article reviews 3 of the most widely used LVADs for bridge to transplant therapy: the Thoratec; HeartMate vented electric; and the Novacor Left Ventricular Assist System. Indications, mechanism of operation, clinical problems, and out-of-hospital preparation are outlined.


Seroprevalence of Coxiella burnetii in selected populations of domestic ruminants in Newfoundland.
The seroprevalence of Coxiella burnetii among cattle, sheep, and goats in Newfoundland was determined by microimmunofluorescence. Seropositivity to phase II antigen increased in sheep from 3.1% in 1997 to 23.5% in 1999-2000 (P < 0.001). Cows (24%) had antibodies to phase I antigen; goats (15.6%) had antibodies to phase II antigen. Seroprevalence of C. burnetii is increasing among sheep.


[Increased expression of SEMA5B in gastric adenocarcinoma predicts poor prognosis: a study based on TCGA data].
Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio(HR) of 1.042 (95%CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95%CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.


A pica case confused with renal and bladder stones.
Pica is considered as an eating-nutritional disorder in childhood and is generally analysed within obsessive-compulsive disorders. A 15-year-old female patient was admitted to the urology clinic with nausea, vomiting, and stomach-ache. A 23 x 23 mm opacity was identified in left T-11-12 level in direct urinary graph. Full abdomen ultrasonography was reported to be normal. Later, it was learned that the patient had the habit of eating stone. The patient was diagnosed with obsessive-compulsive disorder following psychiatric consultation, and appropriate treatment was given.


Context is everything: Mining the normal and preneoplastic microenvironment for insights into the diet and cancer risk conundrum.
This review highlights the context-dependence of epithelial carcinogenesis in order to illuminate the potential for progress in the field of diet and cancer prevention. Estimates drawn from observational epidemiology imply that diet and lifestyle changes have the potential to prevent 30-40% of cancer cases. However, the application of knowledge gleaned from observational epidemiology applied to randomized clinical trials (RCT) has yielded equivocal or negative results. Resolving this conundrum requires: (i) advances in diet assessment methodologies and the design of clinical trials; (ii) greater knowledge of the active components within foods which may impact cancer risk; and (iii) knowledge about the effects of dietary components on susceptible tissues throughout the disease process (Meyskens, F. L., Jr., Szabo, E., Diet and cancer: The disconnect between epidemiology and RCT. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1366-1369). Explicit consideration of the causal criteria will pay tangible benefits in the design of basic, clinical, and epidemiologic studies in cancer prevention. The rational identification of diet-dependent physiologic targets for cancer prevention is best pursued by appreciating context-dependence of epithelial carcinogenesis. Five contexts, or paradigms useful in understanding the multifactorial nature of carcinogenesis, are offered which describe the potential diet-associated physiologic influences on normal and preneoplastic cells and tumor microenvironments. Taken together with the interactions of systemic, endocrine, and autocrine/paracrine signals that may modulate the process of carcinogenesis, we can appreciate how dietary factors may act collectively in normal tissues or at early stages of carcinogenesis to prevent cancer. Only by understanding the effect of dietary components on the cellular and stromal components of the tissue microenvironment early in the process of epithelial carcinogenesis will yield clues useful for the development of improved strategies for cancer prevention.


Resuscitative endovascular balloon occlusion of the aorta (REBOA): indications: advantages and challenges of implementation in traumatic non-compressible torso hemorrhage.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is regaining popularity in the treatment of traumatic non-compressible torso bleeding. Advances in invasive radiology coupled with new damage control measures assisted in the refinement of the technique with promising outcomes. The literature continues to have substantial heterogeneity about REBOA indications, applications, and the challenges confronted when implementing the technique in a level I trauma center. Scoping reviews are excellent platforms to assess the diverse literature of a new technique. It is for the first time that a scoping review is adopted for this topic. Advances in invasive radiology coupled with new damage control measures assisted in the refinement of the technique with promising outcomes. The literature continues to have substantial heterogeneity about REBOA indications, applications, and the challenges confronted when implementing the technique in a level I trauma center. Scoping reviews are excellent platforms to assess the diverse literature of a new technique. It is for the first time that a scoping review is adopted for this topic. Critical search from MEDLINE, EMBASE, BIOSIS, COCHRANE CENTRAL, PUBMED and SCOPUS were conducted from the earliest available dates until March 2018. Evidence-based articles, as well as gray literature at large, were analyzed regardless of the quality of articles. We identified 1176 articles related to the topic from all available database sources and 57 reviews from the gray literature search. The final review yielded 105 articles. Quantitative and qualitative variables included patient demographics, study design, study objectives, methods of data collection, indications, REBOA protocol used, time to deployment, zone of deployment, occlusion time, complications, outcome, and the level of expertise at the concerned trauma center. Growing levels of evidence support the use of REBOA in selected indications. Our data analysis showed an advantage for its use in terms of morbidities and physiologic derangement in comparison to other resuscitation measures. Current challenges remain in the selective application, implementation, competency assessment, and credentialing for the use of REBOA in trauma settings. The identification of the proper indication, terms of use, and possible advantage of the prehospital and partial REBOA are topics for further research. Level III.


Multiple comparisons.
Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield.


Oleanolic acid and related triterpenoids from olives on vascular function: molecular mechanisms and therapeutic perspectives.
Oleanolic acid and related triterpenoids from olives modulate different signaling pathways, showing a wide range of pharmacological activities against inflammation, cancer or cardiovascular diseases. In particular, emerging evidences reveal the potential of oleanolic acid to restore vascular disorders associated to cardiovascular risk factors, i.e. hypertension, obesity and diabetes, and atherosclerosis. During the previous years, in vitro and in vivo studies with these triterpenoids have positioned them as being mainly responsible for cardiovascular risk protection traditionally associated to olive oil. This review updates recent investigations in olive oil triterpenoids function related to cardiovascular diseases, as well as the underlying mechanisms and structural implications. Important aspects of olive oil triterpenoids such as bioavailability and clinical perspectives on cardiovascular disorder are also extensively analyzed. All these investigations evidence the potential of triterpenoids from olive oil as a promising therapeutic strategy against vascular function, thus efficiently preventing the progression of cardiovascular diseases.


Determinants of Mortality in Patients with Acute Kidney Injury Caused by Coronavirus Disease 2019 Infection in a Tertiary Care Hospital of South India.
Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19), and its severity is linked to the adverse outcomes of multiorgan involvement. We attempted to assess the clinical outcomes and determinants of mortality in patients admitted to our COVID-19 care center from May to November 2020 who developed AKI through a retrospective examination of their case records. The data of those who developed AKI were analyzed for their clinical parameters, clinical presentation, history, laboratory parameters, urine output measurements, requirements for dialysis, treatment, and treatment outcomes (discharge or death). These outcomes were correlated to the comorbidities, laboratory parameters, the Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, sequential organ failure assessment score, and need for dialysis or renal replacement therapy. Of 1890 patients admitted, 132 (6.98%) patients developed AKI. Of 450 deaths from all causes, 67 (14%) were in AKI patients. There were 100 (75.8%) males and 32 (24.8%) females. The mean age was 62.05 ± 11.48 years. The median duration of stay was 7 days (interquartile range: 4--11.75 days). The number of patients in AKI Stages 1, 2, and 3 was 1 (0.75%), 64 (48.48%), and 67 (50.75%), respectively. The most common symptoms were breathlessness (85.6%), fever (84.5%), myalgia (81.19%), and weakness (76.5%). Multivariate analysis showed that the determinants of mortality were a partial pressure of oxygen saturation (pO2) of <75% and of 76%-85% compared with a pO2 of >85%, not receiving remdesivir, and KDIGO Stage >2.


Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid.
As the key producer of cerebrospinal fluid (CSF), the choroid plexus (CP) provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2), as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP) in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic) led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.


Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer.
The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC-MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.


Lamotrigine in the treatment of pain syndromes and neuropathic pain.
Anti-epileptic drugs are increasingly used in the treatment of pain syndromes and neuropathic pain. Sodium channel blockers can be effective in the treatment of pain. The object of our interest is the efficiency of lamotrigine in treating the pain. A MEDLINE search was conducted to identify pertinent studies, case reports, letters, and reviews in English published from 1986 to May 2007. The search has indicated efficiency in treating a number of painful syndromes and neuropathic pain; central pain, trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis, pain in multiple sclerosis, SUNCT syndrome, cluster headache, glossopharyngeal neuralgia, neuropathic pain, allodynia, neuralgia after nerve section, postherpetic neuralgia, HIV-associated neuropathy. Further researches are required on the role of lamotrigine in treating the spinal cord injury pain, neuralgia after nerve section, postoperative analgesic requirement, and in migraine (Tab. 1, Ref. 46). Full Text (Free, PDF) www.bmj.sk.


Positive youth development, life satisfaction, and problem behaviors of adolescents in intact and non-intact families in Hong Kong.
This study investigated whether Chinese adolescents living in intact and non-intact families differed in their positive development, life satisfaction, and risk behavior. A total of 3,328 Secondary 1 students responded to measures of positive youth development (such as resilience and psychosocial competencies), life satisfaction, and risk behavior (substance abuse, delinquency, Internet addiction, consumption of pornographic materials, self-harm, and behavioral intention to engage in problem behavior). Findings revealed that adolescents growing up in intact families reported higher levels of positive developmental outcomes and life satisfaction as compared with adolescents from non-intact families. Adolescents in non-intact families also reported higher levels of risk behaviors than those growing up in intact families.


O-polysaccharide glycosylation is required for stability and function of the collagen adhesin EmaA of Aggregatibacter actinomycetemcomitans.
Aggregatibacter actinomycetemcomitans is hypothesized to colonize through the interaction with collagen and establish a reservoir for further dissemination. The trimeric adhesin EmaA of A. actinomycetemcomitans binds to collagen and is modified with sugars mediated by an O-antigen polysaccharide ligase (WaaL) that is associated with lipopolysaccharide (LPS) biosynthesis (G. Tang and K. Mintz, J. Bacteriol. 192:1395-1404, 2010). This investigation characterized the function and cellular localization of EmaA glycosylation. The interruption of LPS biogenesis by using genetic and pharmacological methods changed the amount and biophysical properties of EmaA molecules in the outer membrane. In rmlC and waaL mutant strains, the membrane-associated EmaA was reduced by 50% compared with the wild-type strain, without changes in mRNA levels. The membrane-associated EmaA protein levels were recovered by complementation with the corresponding O-polysaccharide (O-PS) biosynthetic genes. In contrast, another trimeric autotransporter, epithelial adhesin ApiA, was not affected in the same mutant background. The inhibition of undecaprenyl pyrophosphate recycling by bacitracin resulted in a similar decrease in the membrane-associated EmaA protein. This effect was reversed by removal of the compound. A significant decrease in collagen binding activity was observed in strains expressing the nonglycosylated form of EmaA. Furthermore, the electrophoretic mobility shifts of the EmaA monomers found in the O-PS mutant strains were associated only with the membrane-associated protein and not with the cytoplasmic pre-EmaA protein, suggesting that this modification does not occur in the cytoplasm. The glycan modification of EmaA appears to be required for collagen binding activity and protection of the protein against degradation by proteolytic enzymes.


Overall kinetic mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae.
Kinetic data have been measured for the histidine-tagged saccharopine dehydrogenase from Saccharomyces cerevisiae, suggesting the ordered addition of nicotinamide adenine dinucleotide (NAD) followed by saccharopine in the physiologic reaction direction. In the opposite direction, the reduced nicotinamide adenine dinucleotide (NADH) adds to the enzyme first, while there is no preference for the order of binding of alpha-ketoglutarate (alpha-Kg) and lysine. In the direction of saccharopine formation, data also suggest that, at high concentrations, lysine inhibits the reaction by binding to free enzyme. In addition, uncompetitive substrate inhibition by alpha-Kg and double inhibition by NAD and alpha-Kg suggest the existence of an abortive E:NAD:alpha-Kg complex. Product inhibition by saccharopine is uncompetitive versus NADH, suggesting a practical irreversibility of the reaction at pH 7.0 in agreement with the overall K(eq). Saccharopine is noncompetitive versus lysine or alpha-Kg, suggesting the existence of both E:NADH:saccharopine and E:NAD:saccharopine complexes. NAD is competitive versus NADH, and noncompetitive versus lysine and alpha-Kg, indicating the combination of the dinucleotides with free enzyme. Dead-end inhibition studies are also consistent with the random addition of alpha-Kg and lysine. Leucine and oxalylglycine serve as lysine and alpha-Kg dead-end analogues, respectively, and are uncompetitive against NADH and noncompetitive against alpha-Kg and lysine, respectively. Oxaloacetate (OAA), pyruvate, and glutarate behave as dead-end analogues of lysine, which suggests that the lysine-binding site has a higher affinity for keto acid analogues than does the alpha-Kg site or that dicarboxylic acids have more than one binding mode on the enzyme. In addition, OAA and glutarate also bind to free enzyme as does lysine at high concentrations. Glutarate gives S-parabolic noncompetitive inhibition versus NADH, indicating the formation of a E:(glutarate)2 complex as a result of occupying both the lysine- and alpha-Kg-binding sites. Pyruvate, a slow alternative keto acid substrate, exhibits competitive inhibition versus both lysine and alpha-Kg, suggesting the combination to the E:NADH:alpha-Kg and E:NADH:lysine enzyme forms. The equilibrium constant for the reaction has been measured at pH 7.0 as 3.9 x 10(-7) M by monitoring the change in NADH upon the addition of the enzyme. The Haldane relationship is in very good agreement with the directly measured value.


Mechanism of One-to-Many Molecular Recognition Accompanying Target-Dependent Structure Formation: For the Tumor Suppressor p53 Protein as an Example.
The new type of molecular recognition, in which an intrinsically disordered region (IDR) of a protein binds to many different target proteins with target-dependent structure formation, is indispensable to the expression of life phenomena and also implicated in a number of diseases. According to the prevailing view, the physicochemical factors responsible for the binding are also target dependent. Here we consider an IDR of the tumor suppressor p53 protein, p53CTD, as an important example related to carcinogenesis and analyze its binding to four targets accompanying the formation of target-dependent structures (i.e., helix, sheet, and two different coils) using our statistical-mechanical method combined with molecular models for water. We find that all of the seemingly different binding processes are driven by a large gain of the translational, configurational entropy of water in the system. The gain originates from sufficiently high shape complementarity on the atomic level within the p53CTD-target interface. It is also required that the electrostatic complementarity be ensured as much as possible to compensate for the dehydration. Such complementarities are achieved in harmony with the portion of the target to which p53CTD binds, leading to a large diversity of structures of p53CTD formed upon binding: If they are not achievable, the binding does not occur. This finding is made possible only by calculating the changes in thermodynamic quantities upon binding and decomposing them into physically insightful components.


Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma.
Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma. This is a single institution analysis of all patients with T2-T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models. A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2-109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively. This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved.


Noninvasive Methods for Intracranial Pressure (ICP) Monitoring in Traumatic Brain Injury Using Transcranial Doppler (TCD): A Scoping Review.
Intracranial pressure (ICP) monitoring is necessary for managing patients with traumatic brain injury. Although gold-standard methods include intraventricular or intraparenchymal transducers, these systems cannot be used in patients with coagulopathies or high risk of catheter-related infections nor in resource-constrained settings. Thus, a noninvasive modality that is more widely available, cost-effective, and safe would have tremendous impact. Among such noninvasive choices, transcranial Doppler (TCD) provides indirect ICP estimates through waveform analysis of cerebral hemodynamic changes. The objective of this scoping review is to describe the existing evidence for the use of TCD-derived methods in estimating ICP in adult TBI patients as compared to gold-standard invasive methods. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies conducted in adult TBI patients published in any language between 2012 and 2022. 22 studies were included for analysis, with most being prospective studies conducted in high-income countries. TCD-derived nICP methods are either mathematical or non-mathematical, with the former having slightly better correlation with invasive methods, especially when using time-trending ICP dynamics over one-time estimated values. Nevertheless, mathematical methods are associated with greater cost and complexity in their application. Formula-based methods showed promise in excluding elevated ICP, exhibiting a high negative predictive value. Thus, TCD-derived methods could be useful in assessing ICP changes instead of absolute ICP values for high-risk patients, especially in low-resource settings.


Sound generation in gradient coil structures for MRI.
When supporting plates of plastic material are subjected to alternating transverse Lorentz forces while in a strong magnetic field normal to the plate surface, compressional waves within the solid produce a modulation of the plate surface that launches an acoustic wave in air along the magnetic field axis. We have extended our previous theory describing this process to include a detailed description of the formation of an acoustic interference pattern in air described by Fraunhofer diffraction at a distance from the plate surface. The extended theory predicts that the observed acoustic signal midpoint and normal to the plate surface gives a variation with frequency in approximate agreement with our previous measurements. The acoustic output off axis shows acoustic blazing that produces two main diffraction peaks with a splitting inversely proportional to the velocity of sound in the plate material. The new results could have important ramifications for the minimization of sound output in gradient coil design for MRI. A new arrangement of coils is proposed to ameliorate the acoustic output problem centrally and normal to the plate by extending the frequency response of the supporting plates to much higher frequencies. Also presented are estimates of the compressional wave velocities deduced from frequency response data recorded at the center-point of a number of different plates.


Computerised clinical decision support system for the diagnosis of pulmonary thromboembolism: a preclinical pilot study.
Recommendations for the diagnosis of pulmonary embolism are available for healthcare providers. Yet, real practice data show existing gaps in the translation of evidence-based recommendations. This is a study to assess the effect of a computerised decision support system (CDSS) with an enhanced design based on best practices in content and reasoning representation for the diagnosis of pulmonary embolism. Randomised preclinical pilot study of paper-based clinical scenarios in the diagnosis of pulmonary embolism. Participants were clinicians (n=30) from three levels of experience: medical students, residents and physicians. Participants were randomised to two interventions for the diagnosis of pulmonary embolism: a didactic lecture versus a decision tree via a CDSS. The primary outcome of diagnostic pathway concordance (derived as a ratio of the number of correct diagnostic decision steps divided by the ideal number of diagnostic decision steps in diagnostic algorithms) was measured at baseline (five clinical scenarios) and after either intervention for a total of 10 clinical scenarios. The mean of diagnostic pathway concordance improved in both study groups: baseline mean=0.73, post mean for the CDSS group=0.90 (p<0.001, 95% CI 0.10-0.24); baseline mean=0.71, post mean for didactic lecture group=0.85 (p<0.001, 95% CI 0.07-0.2). There was no statistically significant difference between the two study groups or between the three levels of participants. A computerised decision support system designed for both content and reasoning visualisation can improve clinicians' diagnostic decision-making.


Dr. Yukihiko Nosé: living his dream.
Dr. Yukihiko Nosé made many contributions to medical science and in particular in the area of artificial organ technologies and their clinical applications. His passing was a great loss not only to many individuals but also to the field. His enthusiasm and passion for his work was very positive on those with whom he worked while inspiring others in friendly competition. It is very difficult to recount his many accomplishments. I have outlined those developments that I was directly involved with him at the Cleveland Clinic. These developments may be grouped under the heading of Metabolic and Immunologic Support, the name given to our research team. I hope in some small way this review also gives credit to the contributions of the many scientific and clinical professionals that were part of our teams through the years as noted in the extensive reference list provided and the support of the many industrial and corporate sponsors that we were privileged to be associated with and their developments that we studied, improved on, and applied.


Immunodeficiency due to defects of polymorphonuclear leukocyte function.
Functional defects of polymorphonuclear leukocytes can lead to clinical immunodeficiency. Understanding these conditions requires a knowledge of normal polymorph physiology and the means to analyse various aspects of polymorph function. Primary diseases of polymorph function are rare, whereas disorders secondary to other diseases are more common. Prompt diagnosis of these conditions leads to better patient management.


Influence of Crystal Water on Crystal Structure, Electronic Structure, Band Structure, and Charge Separation of WO3·2H2O Nanosheets.
In this work, we mainly investigate the influence of structure water on crystal structure, electronic structure, band structure, and charge separation of WO3·2H2O. It is found, for the first time, that although water is a weak electron donor, a ligand-to-metal charge transfer (LMCT) from H2O to W occurs. The structure water contributes to the conduction band (CB) of WO3·2H2O, and the band gap of WO3·2H2O is obviously narrowed, thus increasing the light absorption obviously. Moreover, the results of EIS, photocurrent spectra, and PL show that structure water in WO3·2H2O also improves the charge separation and transfer efficiency of the catalyst. This is the first investigation on the LMCT transfer from structure water (a weak electron donor) to tungsten, which obviously improves light absorption and charge separation. Under visible light irradiation (λ ≥ 420 nm), WO3·2H2O nanosheets have a photocatalytic activity 2.3 times higher than that of WO3 for the degradation of methylene blue (MB). The kind number of photochemical materials can be increased greatly, because structure water-contained compounds widely exist in nature.


[Study of rifampicin resistance in L-forms of Mycobacterium tuberculosis, by analyzing rpoB gene mutations].
Twenty-nine Mycobacterium tuberculosis (MBT) L-form strains isolated from biopsy and surgery samples taken in 27 patients with extrapulmonary tuberculosis were studied. Since a direct examination of the resistance of L-forms is impossible due to their in vitro culturing features, it is expedient to use molecular genetic methods, by studying rpoB gene mutations. The study showed a high mutation rate (89.7%) in MBT L-forms associated with rifampicin resistance. The findings correlate with the recent years' monitoring of drug resistance in MBT in extrapulmonary tuberculosis, which has indicated that the total resistance of MBT from the foci of this form of tuberculosis to antituberculous drugs is as high as 90% and multidrug resistance is 30%. Moreover, the mycobacterial population was found to be heterogeneous. The ratio of rifampicin-resistant L-forms to sensitive ones in the established heterogeneity of the mycobacterial population calls for further studies.


Improved sizing of fragile X CCG repeats by nested polymerase chain reaction.
We have developed an improved method for polymerase chain reaction (PCR)-based sizing of the CCG repeat region at the fragile X locus, FMR-1. This method is designed to optimize denaturation and replication of long repeats with high G + C content, which are otherwise refractory to amplification. The method utilizes nested PCR primers to increase sensitivity and specificity. Alkaline denaturation of the genomic template DNA, combined with addition of glycerol and deaza-dGTP, facilitates strand separation. Labeled PCR products are sized on denaturing polyacrylamide gels. For alleles in the normal-to-premutation size range, strong reproducible signals are routinely obtained from small amounts of rapidly prepared DNA. This allows precise determination of the CCG repeat number, providing data related to the expansion potential of the repetitive segment. Detection of large premutations and some full mutations is also enhanced by the improved procedure.


Disambiguation of Isomeric Procyanidins with Cyclic B-Type and Non-cyclic A-Type Structures from Wine and Peanut Skin with HPLC-HDX-HRMS/MS.
Hydrogen/deuterium exchange coupled with high-resolution mass spectrometry was successfully applied for the identification of A-type tetrameric, pentameric, and hexameric procyanidins in peanut skin. This extended a previous study on isomeric cyclic B-type unconventional tetramer, pentamer, and hexamer procyanidins found in wine and cranberries. Not only had the method successfully identified the procyanidins with a single A-linkage (e.g., tetrameric m/z 1153.2608) by means of distinguishing them from their isomeric cyclic B-type analogues, but this method also worked for procyanidins with two or more A-linkages (such as the tetrameric m/z 1151.2452). As a further consequence, B-type cyclic pentamers and hexamers in wine have been elucidated with hydrogen/deuterium exchange (HDX) for the first time. Graphical Abstract .


Pharmaceutical interventions for the management of no-reflow.
A common complication of percutaneous coronary intervention (PCI), no-reflow is predominantly encountered during interventions in degenerated saphenous vein grafts and is associated with a marked increase in short-term mortality risk. Etiologically, no-reflow is complex and multifactorial. Microembolic debris from dilated target sites, sustained diffuse microvascular spasm, and pathophysiologic alterations from initial ischemic insults and subsequent reperfusion injuries result in persistence of myocardial ischemia despite angiographic evidence of restored vessel patency. Treatments to prevent or reverse no-reflow include antiplatelet medications to interfere with platelet aggregation. However, insufficient evidence exists demonstrating benefits with their prophylactic use in humans. Distal protection devices target microemboli, but soluble vasoactive factors may elude capture, contributing to downstream vasospasm. Intracoronary administration of vasodilators during PCI address a root cause of no-reflow. Adenosine, nitroprusside, verapamil, nicardipine and others have been evaluated clinically, showing improvements across a range of surrogate TIMI flow grade and frame count and real endpoints (wall motion indices and elevated CPK). Nicardipine may be particularly well-suited for prevention or reversal of no-reflow, demonstrating pharmacologic protection equal or superior to mechanical distal protection devices. The consistent and often dramatic mitigation of no-reflow by adjunctive use of vasodilators supports the role of microvascular spasm as a major, modifiable cause of the syndrome and a critical therapeutic target. A further large-scale, prospective, randomized, controlled clinical study is warranted to confirm prior findings, determine the optimal dosing regimen, and whether treatment or prevention of no-reflow confers clinically relevant outcome benefits.


Mechanistic variations in the oxidation of Piloty's acid by metal complexes.
The reactions of N-hydroxybenzenesulfonamide (Piloty's acid, PA) with a variety of metal oxidants are reported. Either nitric oxide or nitrite is the final reaction product, along with benzenesulfinate and the reduced metal compound. The nitrogen product depends on the oxidation potential of the metal oxidant and its ability to further oxidize NO to nitrite. The observation and preliminary interpretation of unusual kinetic behavior of Piloty's acid as a reductant is also described. Analogues of PA were also prepared and found to show similar reactivity.


Monte Carlo simulation of genome viability with paralog replacement.
Recent analyses of genome content have revealed that many single functions, even in haploid organisms, can be executed by more than one gene. As a result, experimental disruption of many individual genes does not exert lethal effects on the organism or even any visible change in the phenotype of the organism with a knockedout gene. Our analysis shows that such genetic redundancy allows for an appreciably higher mutation load in the genome simulations before the viability of the whole organism is destroyed.


Probing the buried C60/Au(111) interface with atoms.
To characterize the C(60)/Au(111) interface, we send Au atoms "diving" through the C(60) layer and observe their behavior at the interface. Our observations show that the interfacial diffusion of gold atoms and the nucleation of small Au islands at the interface are strongly dependent on the local C(60)-Au(111) bonding which varies from one domain to another. The contrast-disordered domain consisting of a large fraction of molecules bonded to Au vacancies has a special structure at the interface allowing Au atoms to be inserted beneath the bright-looking molecules while the dim molecules present a much stronger resistance to the diffusing Au atoms. This leads to the formation of isolated Au islands with discrete sizes, with the smallest island just about 1 nm across.


Insights into genetic and epigenetic determinants with impact on vitamin d signaling and cancer association studies: the case of thyroid cancer.
Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer (TC), we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR) in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signaling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the revaluation of the potential preventive and anticancer properties of vitamin D in TC.


Diaphragmatic breathing exercises in recovery from fatigue-induced changes in spinal mobility and postural stability: a study protocol.
Prolonged periods of sitting at work can increase trunk muscle fatigue from the continuous contraction of deep trunk muscles. Insufficient activity of these muscles can decrease muscular support to the spine and increases stress on its passive structures. This can lead to reduced spinal mobility and impaired postural stability. It may also stimulate nociceptor activity leading to pain. However, frequently used recovery modalities such as muscle strengthening and stretching exercises, can be time-consuming, impractical, and difficult to implement in the workplace. Diaphragmatic breathing exercises, which increase the activity of the deep trunk muscles by raising intra-abdominal pressure, seem to be a suitable alternative. However, little is known as to what extent diaphragmatic breathing exercises contribute to the reduction of fatigue induced by prolonged sitting. This paper presents a study protocol that aims to investigate the acute effect of diaphragmatic breathing exercises on recovery of fatigue-induced changes in spinal mobility and postural stability in sedentary middle-aged adults at risk of developing non-specific low back pain. Twenty sedentary adults aged between 25 and 44 years will perform Abt's fatigue protocol, followed by 1) active recovery using diaphragmatic breathing exercises and 2) passive recovery in the form of lying on the bed, respectively. There will be 1 week of rest in-between. Pre-fatigue, post-fatigue, and after the active and passive recovery, spinal mobility and postural stability will be evaluated using the spinal mouse device and a posturography system, respectively. The electromyography will be used to determine the muscle-fatigue conditions. We hypothesize that active recovery in a form of diaphragmatic breathing exercises would be more effective in restoring spinal mobility and postural stability followed by the fatigue of back and hamstring muscles compared to passive recovery in sedentary adults. Increasing core and respiratory muscle strength via these exercises could be beneficial for overall mobility and stability of the spine. Reducing compressive stress on the passive structures of the spine may be also beneficial for lowering low back pain. Therefore, we believe that diaphragmatic breathing exercises have the possibility to be incorporated into the workplace and contribute to better back health in sedentary middle-aged adults. Clinical Trial Registration: [https://www.irct.ir/trial/67015], identifier [IRCT20221126056606N1].


[Analysis of detection rate and compliance of colorectal cancer screening with colonoscopy in urban areas of Henan Province, 2013-2019].
Objective: To evaluate the compliance of colonoscopy screening and the detection rate of colorectal lesions with colonoscopy in urban areas of Henan province from 2013 to 2019. Methods: The study objects were derived from the Cancer Screening Program in Urban Henan Province, China. From October 2013 to October 2019, 282 377 residents, who had lived in the local area for more than three years, were recruited from Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Puyang and Xinxiang. The cancer risk assessment questionnaire was used to collect basic demographic characteristics, eating habits, living environment and habits, psychology and emotions, past disease history and family history of cancer, and women's physiological and reproductive history. The cancer risk assessment model was used for evaluating the risk of colorectal cancer. The data related to colonoscopy screening was obtained from the participating hospitals. Chi-square test was used to analyze the compliance rate among different groups. Results: The 282 377 subjects were (55.26±8.68) years old, of which 44.80% (126 505) were males, and 67.63% (190 694) had junior/senior/tertiary education background. A total of 39 834 (14.11%) subjects were assessed to be at high risk for colorectal cancer, of which 7 454 took the following colonoscopy screening, yielding a participation rate of 18.71%. The screening rate was higher in those aged 50 to 54 (20.42%) and 55 to 59 (20.43%) years, and lowest in those aged 70 years and older (12.30%) (P<0.001). A total of 17 colorectal cancer cases were detected, with a detection rate of 0.23% (17/7 454). Conclusion: Colonoscopy as a means of screening for colorectal cancer is helpful for early detection of colorectal lesions, but the participation rate is poor.


The catalytic cycle of cytochrome P-450scc and intermediates in the conversion of cholesterol to pregnenolone.
Cytochrome P-450scc as isolated is a cholesterol-depleted low-spin haemoprotein; addition of cholesterol results in formation of a high-spin complex. Cytochrome P-450scc--cholesterol is a one-electron acceptor on titration with NADPH. Cytochrome P-450scc--cholesterol can be anaerobically reduced to the ferrous state which, on oxygenation, forms an oxygenated cytochrome P-450scc--cholesterol complex. This oxygenated complex in the absence of adrenodoxin autoxidises to ferric cytochrome P-450scc--cholesterol without oxidation of cholesterol. The decay of the oxygenated complex is first-order, k = 9.3 X 10(-3) S-1 at 4 degrees C. The rate of autoxidation is influenced by pH, ionic strength and the chemical nature of bound sterol. The activation energy of autoxidation is 75 kJ mol-1. Addition of equimolar amounts of adrenodoxin to cytochrome P-450scc--cholesterol followed by stoichiometric reduction under anaerobic conditions and subsequent oxygenation, allows single catalytic turnover cycles of cytochrome P-450scc to be observed. This has led to detection of intermediates in the conversion of cholesterol to pregnenolone and a precursor/product sequence of cholesterol----22-hydroxycholesterol----20,22-dihydroxy-cholesterol ----pregnenolone has been established. Addition of oxidised adrenodoxin to oxygenated cytochrome P-450scc--cholesterol results in formation of 22-hydroxycholesterol.


[Evaluation of the effectiveness of endovascular embolization for the treatment of ruptured cerebral aneurysms].
Endovascular embolization of ruptured intracranial aneurysms is a relatively new and still developing technique, therefore its efficiency and risks should be assessed recurrently, including also results obtained in national centers. The aim of the study was to present a synthetic review of the literature, which, including the data published by the Polish centers, typify the global assessment of the effectiveness and early complication of endovascular embolization in patients with ruptured brain aneurysms. Our review of the literature includes 24 papers listed in PubMed and Medline, including also two Polish case series. The following data were extracted from the publications and compiled into global characteristics of a case series: basic characteristic of the study group, neurological status on admission, feasibility of procedure, incidence of complications and their type, outcome at discharge and intraoperative morbidity and mortality. Effective embolization was feasible in 94.4% of patients. Total occlusion of the cerebral aneurysm (99-100%) during initial procedure was achieved in 60.7% of patients. Intraoperative complications occurred in 12.6% of individuals. The most frequent type of intraoperative complication was thromboembolism, which occurred in 6%. As much as 65.2% of patients scored 4 or 5 in GOS on discharge. Endovascular embolization is highly effective in the treatment of ruptured cerebral aneurysms, featured also by a low rate of intra-procedural complications. The majority of patients are discharged in good shape and neurological status, scoring 4-5 in GOS.


Tissue-microarray based immunohistochemical analysis of survival pathways in nodular sclerosing classical Hodgkin lymphoma as compared with Non-Hodgkin's lymphoma.
Neoplastic cells rely on key oncogenic pathways for their gain of proliferative and/or loss of apoptotic potential. Therapy targeted at specific points in these pathways has the potential to eliminate cancer cells by inducing differentiation or apoptosis. Concurrent immunophenotypic evaluation of survival pathways in nodular sclerosing classical Hodgkin lymphoma (cHL-NS) tissues has not previously been undertaken. We took the tissue microarray (TMA)-based approach to retrospectively evaluate the activation state of key oncogenic pathways by immunohisto-chemistry (IHC) in a series of 6 cases of cHL-NS (with predominantly syncitial areas). For comparison, 2 cases of diffuse large B-cell lymphoma (DLBCL), and 1 case of follicular hyperplasia (FH) were included in the study. Infiltration of T regulatory cells (Tregs) in the tumor microenvironment was assessed by expression of the Foxp3 transcription factor. Differential upregulation of the mitogen-activated protein kinase (MAPK)-extracellular signal related kinase (ERK), signal transducers and activators of transcription (STAT)3, and protein kinase c - alpha (PKC-alpha) pathways was seen among the cHL cases, whereas nuclear factor - kappa B (NF-kB) and phosphoinositide 3 kinase (PI3 K)-AKT-mammalian target of rapamycin (mTOR) pathways were equally activated in the neoplastic Reed-Sternberg cells of the 6 cHL-NS cases. Marked difference in the morphoproteomic profile was seen amongst the two cases of DLBCL. The amount of Foxp3+ T regulatory cells (Tregs) in the tumor microenvironment was highly variable ranging from 6/hpf to 120/hpf in cHL-NS, and 1/hpf to 82/hpf in DLBCL. In this pilot study, concurrent evaluation of oncogenic pathways in cHL-NS and DLBCL offers powerful insights in the putative therapeutic targets for an individualized approach to diagnosis and therapy.


lncRNA H19 Promotes Ox-LDL-Induced Dysfunction of Human Aortic Endothelial Cells through the miR-152/VEGFA Axis.
lncRNA H19 (H19) elevation is related to the risk of coronary artery disease. DIANA-lncBase database analysis suggested that microRNA-152 (miR-152) and H19 have binding sites. Here, the effect and mechanism of H19 and miR-152 in the oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) were explored. The expression of H19, miR-152, and vascular endothelial growth factor (VEGF)-A in the HAECs treated with 5 μg/mL ox-LDL was detected by qRT-PCR. MTT, wound-healing assay, and tube formation assay were analyzed to evaluate the angiogenic activity of H19 and miR-152 in the HAECs cells knocked down H19. Dual-luciferase assay was performed to verify the targeting relationship of miR-152 to either H19 or VEGFA, respectively. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and vimentin) and VEGFA protein in the cells. After ox-LDL treatment, the expression of H19 and VEGFA was significantly increased, miR-152 expression was remarkably decreased. H19 was mainly expressed in the cytoplasm of HAECs. Knocking down H19 or overexpression of miR-152 significantly inhibited the cellular proliferation, migration, tube formation, and EMT trend of the HAECs. On the contrary, miR-152 interference reversed H19 silencing-mediated effects in the ox-LDL-induced HAECs. The dual-luciferase assay showed that miR-152 had a targeting relationship with H19 and VEGFA. MiR-152 was negatively corrected with the VEGFA expression. Ox-LDL negatively regulates miR-152 via H19, promotes the expression of VEGFA, and induces the dysfunction of HAECs.


Review: hepatitis B and liver transplantation.
Liver transplantation in hepatitis B virus (HBV)-infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in non-immuno-compromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti-HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that and potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine (2',3',dideoxy,3',thiacytidine) and famciclovir (a guanosine analogue). Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post-transplant HBV recurrence.


Congenital lower lip pits and bilateral clefting of the upper lip.
An apparently sporadic case of congenital lower lip pits in association with upper lip bilateral clefts is described in an 11-month-old boy. The presentation, mode of inheritance, aetiology and genetic significance are briefly reviewed.


The effectiveness of silver-containing hydrofiber dressing compared with topical silver sulfadiazine cream in pediatric patients with deep partial-thickness burns: a retrospective review.
Deep partial-thickness (DPT) burns are a common pediatric burn injury and involve the limbs and trunk. Initial management of a pediatric burn is conservative and consists of wound dressings and creams to optimize the environment for reepithelialization. Silver-containing Hydrofiber dressings (SHDs) and silver sulfadiazine (SS) cream are used widely to treat burn wounds. However, the effectiveness of the 2 methods when applied to pediatric DPT burn wounds is unclear. This study was performed to compare the effectiveness of SHD versus SS cream in pediatric patients with DPT burns. The authors conducted a retrospective review of data collected from 92 pediatric patients (mean age, 51.44 months; range, 2 months to 18 years) with DPT burns to the limbs and trunk involving 5% to 10% of total body surface area who were admitted to a burn center from January 2018 through January 2020; more than 75% of these burns were scald injuries. Of the patients included in this analysis, 40 were treated with topical SS cream, whereas SHDs were used in 52 patients. Outcomes included time to complete healing, number of dressing changes, nursing care time, hospitalization expenses, complications, and patient primary caregiver satisfaction score using a 4-point Likert scale. The complete healing time was significantly shorter in the SHD group compared with the SS group (18.98 ± 2.21 days vs 22.45 ± 2.25 days, respectively; P < .05). There were fewer dressing changes in the SHD group than in the SS group (4 ± 0.74 vs 11.55 ± 0.88, P < .05). Overall, caregivers of patients in the SHD group reported better satisfaction than caregivers in the SS group. When compared with SS cream, the use of SHD was found to be a safe, effective, and economical therapeutic method for treating DPT burns in the pediatric patients included in this study..


Non-Hodgkin's lymphomata: clinical and immunological data in relation to histology.
Two hundred and forty-four previously untreated patients seen since 1964 in the department of haematology at Saint-Louis hospital were analysed. Clinical data included results of initial work-up and prognosis evaluated by survival rate matched with principal variables: age, sex, histopathology, staging, incidence of clinical and biological systemic symptoms. Immunological data included results of systematic studies made in each category of non-Hodgkin's lymphomata. Hyperbasophilic lymphoma, a special group recently characterized, is discussed.


Dynamical model for assessment of anti-angiogenic therapy of cancer.
Different experimental models have substantially established that the anti-angiogenic (AAG)group of drugs are able to control the growth of tumor mass by cutting down the nutritive supply to the cancer cells. The mechanism of action of this group of drugs acts on the cells of the vascular endothelium. Recently, different AAG drugs have been in clinical trials. Initial clinical trials showed that application of AAG drugs produced different sorts of toxicity in patients,so calibration of the doses and drug application schedules are very important at present.Hence, development of analytical models would definitely help in this respect, particularly atthe individual level. The analytical model presented here may help to make a judicious choice of drug doses and drug schedule to control the growth of the tumor system under the condition of malignancy.


THE EVOLUTION OF MATERNAL CHARACTERS.
We develop quantitative-genetic models for the evolution of multiple traits under maternal inheritance, in which traits are transmitted through non-Mendelian as well as Mendelian mechanisms, and maternal selection, in which the fitness of offspring depends on their mother's phenotype as well as their own. Maternal inheritance results in time lags in the evolutionary response to selection. These cause a population to evolve for an indefinite number of generations after selection ceases and make the rate and direction of evolution change even when the strength of selection and parameters of inheritance remain constant. The rate and direction of evolution depend on the inheritance of traits that are not under selection, unlike under classical Mendelian inheritance. The models confirm earlier findings that the response to selection can be larger or smaller than what is possible with simple Mendelian inheritance, and even in a direction opposite to what selection favors. Maternal selection, in which a mother's phenotype influences her offspring's fitness, is frequency-dependent and can cause a population to evolve maladaptively away from a fitness peak, regardless of whether traits are transmitted by Mendelian or maternal inheritance. Maternal selection differs from other forms of selection in that its force depends not only on the fitness function but also on the phenotypic resemblance of parents and offspring.


What does tumour necrosis factor excess do to the immune system long term?
Members of the tumour necrosis factor (TNF)/TNF-receptor (TNF-R) superfamily coordinate the immune response at multiple levels. For example, TNF, LTalpha, LTbeta and RANKL provide signals required for lymphoid neogenesis, CD27, OX-40, 4-1BB and CD30 deliver costimulatory signals to augment immune responses, while pro-apoptotic members such as TNF, CD95L and TRAIL may contribute to the termination of the response. Biological identity of individual family members has been revealed through studies of gain of function or gene deficient mutants. Most notable are the development of spontaneous inflammatory polyarthritis in human TNF-globin transgenic mice, the auto-inflammatory syndromes resulting from mutations in the 55-kDa TNF-R, and, in particular, the obligatory role for the RANKL/RANK axis in osteoclastogenesis and bone remodelling. A growing appreciation of the molecular basis of signalling pathways transduced by TNF-R has provided a framework for better understanding the biology of this expanding family. For while the rapid and robust activation of NF-kappaB and MAPK pathways is typical of acute TNF-R engagement, the molecular basis of sustained receptor signalling remains a mystery, in spite of its relevance to chronic inflammatory and immune responses. Focusing on T cells, this report describes some of the molecular footprints of sustained TNF-R engagement and illustrates how these may influence immune function. A common theme arising is that prolonged TNF stimulation alters signalling thresholds over time. The authors propose that one major outcome of long term exposure to TNF is a state of localised IL-2 deficiency at sites of inflammation. The implications of this deficiency are discussed.


Racial influence on biochemical disease-free survival in men treated with external-beam radiotherapy for localized prostate cancer.
We retrospectively analyzed the clinical characteristics and outcomes of various racial and ethnic groups who underwent radiotherapy alone for localized or locally advanced prostate cancer. From April 1987 to January 1998, 964 patients underwent full-dose, external-beam radiotherapy alone for localized or locally advanced prostate cancer and were included in the study. The patients' medical records were reviewed for pertinent information. Of the 964 patients, 810 were non-Hispanic white, 86 were African-American, 54 were Hispanic, and 14 were Asian. The most significant difference between groups was in the proportion of patients who presented with initial PSA levels > 20 ng/ml. More than 20% of men in all minority groups presented with a serum PSA > 20 ng/ml, compared to only 11% of whites (p = 0.0012). Similarly, 14% of minorities presented with Gleason scores > or = 8 compared to only 11% of whites (p = 0.0265). Hispanic and Asian patients exhibited a higher incidence of Gleason score > or = 8 prostate cancer. When comparing the time intervals of 1995-1998 vs. 1987-1994, the number of men presenting for EBRT with PSA levels < 10 ng/ml increased to 74% from 57% for Caucasians (p < 0,001), 71% from 40% for African Americans (p = 0.012), 67% from 49% for Hispanics (p = 0.1 18), and no change (50%) for Asians. The number of African-American patients presenting with favorable characteristics (PSA < 10 ng/ml) is increasing. These findings suggest that the message of screening and early detection may be reaching the African-American community. Continued diligence in screening and early detection may improve prostate cancer outcome for other minority populations.


Endoscopic Removal of a Cervical Esophageal Duplication Cyst.
A 6-month-old female presented for 2 months of noisy breathing. Flexible laryngoscopy showed limited bilateral vocal fold abduction. Computed tomography revealed a non-enhancing 3.6 × 2.3 × 3.5 cystic prevertebral mass spanning C2-T. Using an endoscopic approach, the overlying mucosa was incised, and the cyst was freed and fully excised from the surrounding mucosa with blunt microlaryngeal instruments without complication. Three months postoperatively she had no respiratory issues and was eating well. Flexible laryngoscopy revealed bilateral vocal fold mobility. We propose that endoscopic removal of a cervical esophageal duplication cyst in selected cases is an alternative to open excision. Laryngoscope, 130:2053-2055, 2020.


Business continuity, emergency planning and special needs: How to protect the vulnerable.
Emergencies and disasters affect all segments of the population. Some segments are more at risk during the emergency response and recovery efforts owing to vulnerabilities that increase the risk of harm. These vulnerabilities are due to individuals' disabilities, which must be incorporated into emergency and business continuity planning. Some disabilities are obvious, such as impaired vision, hearing or mobility, while other are less evident, but equally disabling, such as cognitive disorders, geographical or language isolation, and numerous age-related factors. Taken together when creating emergency or business continuity plans, the issues identified as disabilities can be grouped by functionality and termed as special needs. This paper will detail the identification of special needs populations, explain how these persons are vulnerable during the emergency or disaster response and recovery process, and provide examples of how to partner with individuals within identified special needs populations to improve the planning process.