[Dynamic changes in the response of molluscan neurons to cyclic AMP with repeated injections].
Microiontophoretic injection of cAMP (but not of non-cyclic AMP) into Helix snail neurons induces rapid reversible membrane depolarization. The reversa potential of the cAMP response varies between +10 and -30 mV in different cells. The amplitude of the responses gradually increases (15 experiments), decreases (4 experiments) or remains unchanged (40 experiments) when the interval between the injections is less than 5 minutes. The identified neurons of the different preparations exhibit different types of dynamic changes in the amplitude of the responses to repeated cAMP injections. The possible role of the retaining current in the origin of the potentiation of cAMP responses was investigated. Potentiation of cAMP responses was preserved after the retaining current was switched off only in cases with no membrane depolarization due to spontaneous leakage of the substance from the microelectrode. It is suggested that potentiation or depression of cell responses to repeated cAMP injections is caused by dynamic changes in the cell cAMP system.


Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles.
Golgi membranes and Golgi-derived vesicles are associated with multiple cytoskeletal proteins and motors, the diversity and distribution of which have not yet been defined. Carrier vesicles were separated from Golgi membranes, using an in vitro budding assay, and different populations of vesicles were separated using sucrose density gradients. Three main populations of vesicles labeled with beta-COP, gamma-adaptin, or p200/myosin II were separated and analyzed for the presence of actin/actin-binding proteins. beta-Actin was bound to Golgi cisternae and to all populations of newly budded vesicles. Centractin was selectively associated with vesicles co-distributing with beta-COP-vesicles, while p200/myosin II (non-muscle myosin IIA) and non-muscle myosin IIB were found on different vesicle populations. Isoforms of the Tm5 tropomyosins were found on selected Golgi-derived vesicles, while other Tm isoforms did not colocalize with Tm5 indicating the association of specialized actin filaments with Golgi-derived vesicles. Golgi-derived vesicles were shown to bind to F-actin polymerized from cytosol with Jasplakinolide. Thus, newly budded, coated vesicles derived from Golgi membranes can bind to actin and are customized for differential interactions with microfilaments by the presence of selective arrays of actin-binding proteins.


The effect of fluid flow on selective protein adsorption on polystyrene-block-poly(methyl methacrylate) copolymers.
The effect of fluid flow on protein patterning and the stability of the adsorbed protein array templated by polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) has been investigated. Protein nanoarrays can be formed on a PS-b-PMMA copolymer surface by physisorption and rinsing with an open flow. The protein arrays inherit the original hexagonal pattern generated by the phase separation of PS-b-PMMA with the proteins only residing on the PS domains. Subsequent analysis of the protein array stability under confined flow field reveals that the array integrity is strongly dependent on the flow velocity and the duration time. The interplay between the intermolecular forces and the hydrodynamic shear force has been discussed in detail. A simplified model has been proposed to explain the site-selective adsorption and protein migration under the shear of fluid flow. This study provides valuable information on the formation mechanism and stability of physisorbed protein nanopatterns under conditions concerning biosensing applications. It also represents an explorative study of protein adsorption under hydrodynamic flow conditions, which may assist in better designs of fluidic devices relevant to protein studies.


Polyphenolic characterisation and bioactivity of an Oxalis pes-caprae L. leaf extract.
The present work is focused on the characterisation of the polyphenolic content of an Oxalis pes-caprae L. leaf extract and on the evaluation of its bioactivity with particular interest on its vascular activity and antioxidant potential. The polyphenolic content was characterised by HPLC-DAD and LC-MS/MS. The vascular activity was evaluated according to the influence on the serotonergic and adrenergic systems of the human internal mammary artery (HIMA). Antioxidant and neuroprotective studies were also conducted. Several luteolin and apigenin derivatives were identified as main constituents of the extract, which did not present any contractile effect nor had any effect on the serotonergic system of HIMA. However, it showed antagonistic effect on the adrenergic system, inhibiting the contraction to noradrenaline (reduction of 58.44% of maximum contraction). The extract showed antioxidant activity and standardised luteolin and apigenin derivatives showed neuroprotective potential, particularly homoorientin.


Treatment for patients with rectal cancer and a clinical complete response to neoadjuvant therapy: a decision analysis.
A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility <0.81), or if the relative reduction in recurrence risk with surgery was <43 percent when compared with observation. Our model outlines the issues associated with surgery vs. observation, and suggests that surgery is beneficial for the average patient with rectal cancer with a clinical complete response after neoadjuvant therapy. Current limitations in the clinical assessment of patient response to chemoradiation constitute an important factor influencing our results, and therefore warrant further investigation.


The catalyst-assisted synthesis of high quality CdS single-crystal nanowires through an epitaxy mechanism.
High quality wurtzite CdS nanowires have been synthesized by thermal evaporation of CdS powder onto Si substrate in the presence of Au catalyst at 650 degrees C by using pure H2 as a carrier gas. The nanowires were 10 nm in diameter and a few tens of micrometers in length. XRD patterns demonstrated that as prepared CdS is a pure crystalline material. High-resolution transmission electron microscopy of the materials showed that all CdS nanowires grew along (0001). According to analysis of selective area electron diffraction patterns taken from the interface, we proposed that there is a kind of epitaxy relationship in the interface region between Au catalyst and CdS grown, i.e., (0001)CdS // (111)Au, and [1210]CdS // [011]Au.


Ultraviolet radiation and melanoma.
Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. This article will review the extensive epidemiologic data demonstrating that ultraviolet radiation (UVR) exposure, from the sun or artificial tanning beds, is the most important environmental risk factor for melanoma; the multiple detrimental effects of UVR on human skin, including DNA damage through the formation of dimeric photoproducts, gene mutations, oxidative stress, inflammation, and immunosuppression, all of which contribute to melanomagenesis; and the evidence that protection from UVR exposure, whether by melanin or by sunscreen, reduces the risk of developing melanoma.


Eating disorder age of onset in males: distribution and associated characteristics.
The objective of this study was to determine the distribution of age of onset of eating disorders in males as well as the relationship between age of onset and various clinical and demographic characteristics. The medical records of 70 males consecutively admitted to an inpatient eating disorders unit between June of 1992 and June of 2002 were retrospectively reviewed. Age of onset did not significantly differ by admission diagnosis and appeared to have a single peak at about age 14. Inpatients with older ages of onset reported lower percentage of mean matched population weight (r=-0.35, p=0.005) and longer duration of illness (r=0.26, p=0.03) than inpatients with younger ages of onset. This study confirms the findings of previous investigations performed on female samples and also finds some unique aspects of males with eating disorders important to consider in prevention and treatment programs targeting male populations.


SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing.
Trimethylation of histone H3K36 is a chromatin mark associated with active gene expression, which has been implicated in coupling transcription with mRNA splicing and DNA damage response. SETD2 is a major H3K36 trimethyltransferase, which has been implicated as a tumor suppressor in mammals. Here, we report the regulation of SETD2 protein stability by the proteasome system, and the identification of SPOP, a key subunit of the CUL3 ubiquitin E3 ligase complex, as a SETD2-interacting protein. We demonstrate that SPOP is critically involved in SETD2 stability control and that the SPOP/CUL3 complex is responsible for SETD2 polyubiquitination both in vivo and in vitro ChIP-Seq analysis and biochemical experiments demonstrate that modulation of SPOP expression confers differential H3K36me3 on SETD2 target genes, and induce H3K36me3-coupled alternative splicing events. Together, these findings establish a functional connection between oncogenic SPOP and tumor suppressive SETD2 in the dynamic regulation of gene expression on chromatin.


Potent stimulation of myofilament force and adenosine triphosphatase activity of canine cardiac muscle through a direct enhancement of troponin C Ca++ binding by MCI-154, a novel cardiotonic agent.
In the present study we have analyzed a likely biochemical mechanism underlying the Ca++-sensitizing action of MCI-154 (6-[4-(4'-pyridyl)aminophenyl)-4,5-dihydro-3(2H)-pyridazinone hydrochloride), a novel cardiotonic agent, on the contractile protein system. MCI-154 (10(-7) to 10(-4) M) enhanced the tension development induced by -log molar-free Ca++ concentration (pCa) 5.8 in chemically skinned fiber from the canine right ventricular muscle in a concentration-dependent manner. At pCa 7.0, MCI-154 (10(-7) to 10(-4) M) markedly increased adenosine triphosphatase (ATPase) activities of canine myofibrils and reconstituted actomyosin. In myofibrils and reconstituted actomyosin, MCI-154 (10(-7) to 10(-4) M) caused a parallel shift of the pCa-ATPase activity relation curve to the left without affecting the maximum activity, suggesting an increase in Ca++ sensitivity. MCI-154 (10(-8) to 10(-4) M) had little effect on actin-activated, Mg++, Ca++ and (K+, EDTA)-ATPase activities of myosin. Ca++ binding to cardiac myofibrils or purified cardiac troponin was increased by 10(-4) M MCI-154. These results suggest that MCI-154 enhances Ca++ binding to cardiac troponin C to elevate the Ca++ sensitivity of myofilaments and thus may cause a positive inotropic action in cardiac muscle. MCI-154 may provide a valuable tool for studying the molecular mechanism by which Ca++ regulates the contractile system.


HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors.
The HIV-1 trans-activator Tat increases the rate of transcription from the HIV-1 LTR promoter through the stem-loop-containing TAR RNA. To analyze the mechanisms of Tat action, a cell-free trans-activation system with no preincubation has been developed. Recombinant Tat specifically increased the level of a long runoff transcript but not a promoter-proximal transcript in a TAR-dependent fashion. These observations and the result of pulse-chase experiments support strongly the hypothesis that Tat enhances the ability of RNA polymerase to elongate over longer distances. Increased levels of the purified cellular factor TFIIF, essential for initiation and also implicated in elongation of transcription, obviated trans-activation by Tat by increasing the basal (Tat-independent) activity. However, another elongation factor, ATN/TFIIS, showed synergistic activation with Tat. An antiserum against a recombinant form of the large subunit of TFIIF (RAP 74) preferentially suppressed the activated level of transcription exerted by Tat. We propose the hypothesis that Tat acts as a processivity factor on RNA polymerase II in an analogous manner to TFIIF.


Medical Education During the Coronavirus Disease-2019 Pandemic: Learning From a Distance.
As paradigms of clinical care delivery have been significantly impacted by the novel coronavirus disease-2019 pandemic, so has the structure, delivery, and future of medical education. Both undergraduate and graduate medical education have seen disruptions ranging from fully virtual delivery of educational content and limited clinical care for medical students to increased clinical demands with redeployment for residents and fellows. Adherence to social distancing has led to the adoption and implementation of already available technologies in medical education, including video conferencing softwares and social media platforms. Efficient and effective use of these technologies requires an understanding not only of these platforms and their features but also of their inherent limitations. During a time of uncertainty and increased clinical demands, the approach to medical education must be thoughtful with attention to wellness of both the educator and learner. In this review, we discuss the influence of the pandemic on the existing medical education landscape, outline existing and proposed adaptations to social distancing, and describe challenges that lie ahead.


Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver failure.
Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF.


Adriamycin alters the alkaline phosphatase activity in hamster molars during development in vitro.
The effect of a 2 hour exposure to adriamycin (1 mg/litre) on alkaline phosphatase (ALPase) activity of the golden hamster 4-5 day old second maxillary molars (M2) was investigated in vitro. The molars were grown in BGJb medium containing 15% fetal bovine serum, glutamine (200 micrograms/ml), vitamin C (250 micrograms/ml), penicillin G (50 micrograms/ml), and streptomycin sulphate (30 micrograms/ml). The gas phase contained 50% O2 + 5% CO2 + 45% N2. The molars were supported on cellulosic membrane filters and grown for 3, 5, and 7 days at the medium-gas interface in a closed humidified chamber. Biochemical analysis indicated a steady increase in ALPase activity throughout this study in the control samples. However, after adriamycin treatment no increase in ALPase activity could be observed. The histochemical data showed that the increased activity in the control was confined to the peripheral pulp, sub-odontoblastic layer, stratum intermedium, ameloblasts and odontoblasts. Although these layers showed a decreased activity after adriamycin treatment, the ameloblasts showed an increase in activity over the control. The data has shown that adriamycin caused a reduction in total ALPase activity in developing molars in vitro; osteodentin production by pulp cells; and appeared to produce an acceleration in the differentiation of ameloblasts.


Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.
Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.


Inhibition of human and rat pancreatic proteinases by crude and purified soybean proteinase inhibitors.
Effects of proteinase inhibitors on total proteolytic activity and trypsin and chymotrypsin activity in human pancreatic juice were determined separately. Purified inhibitors as well as crude extracts of raw soybeans completely inhibited trypsin and chymotrypsin activity while 40 to 50% of the total proteolytic activity remained. Inhibition experiments with 1,10-o-phenanthroline showed that this residual proteolytic activity was due mainly to carboxypeptidase A and B. Comparative studies with rat pancreatic enzymes demonstrated certain similarities between the corresponding enzymes from rat and man. However, differences were revealed which indicate that the rat enzymes must be used with great caution when applied as models for the human proteinases when studying effects of soybean inhibitors.


Transconjunctival oxygen monitoring as a predictor of hypoxemia during helicopter transport.
As the use of helicopters for air transport of critically ill patients increases, the availability of monitoring devices for physiological parameters during flight becomes important. It has long been known that arterial PO2 (PaO2) decreases during unsupplemented, non-pressurized flight. In this study, the authors examined the use of the transconjunctival oxygen (cjO2) monitor for assessing the adequacy of arterial oxygenation during helicopter flight in four healthy volunteers. Arterial PaO2 as measured by conventional blood gas analysis was compared with cjO2 at ground level, 5,000 feet, and 10,000 feet altitude. Mean PaO2 dropped significantly from 93.5 to 81.5 to 58.5 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Mean cjO2 also decreased significantly from 63.8 to 52.0 to 34.8 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Within individual subjects, cjO2 was an accurate predictor of PaO2 (P less than 0.001, multiple regression analysis). The relationship between cjO2 and PaO2 was linear with a regression coefficient of 1.147. The authors conclude that the transconjunctival O2 monitor may be useful for monitoring the adequacy of arterial oxygenation during helicopter flight in hemodynamically stable patients. The results of study also support the use of supplemental oxygen in all patients subjected to helicopter transport.


Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children.
With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important during interpretation.


Enhanced renal IGF-I expression following partial kidney infarction.
Renal insulin-like growth factor (IGF)-I expression is enhanced in tissue that remains following removal of kidney mass. To characterize the expression of renal IGF-I after reduction of kidney mass by partial unilateral infarction, we measured levels of IGF-I extracted from noninfarcted (remnant) renal tissue that remained after one-half unilateral kidney infarction that was performed without (1/2NX) or with (1 1/2NX) contralateral nephrectomy. Levels of IGF-I extracted from remnant renal tissue after 1/2NX increased significantly, peaking on day 3 after renal mass reduction, and then returned toward baseline. Steady-state levels of IGF-I mRNA were also elevated on day 3, suggesting that the increase in IGF-I results from enhanced synthesis. A similar pattern of increased extracted IGF-I and elevated IGF-I mRNA occurred after 1 1/2NX. Levels of IGF-I extracted from remnant renal tissue 3 days after 1 1/2NX were not higher than levels extracted from remnant tissue 3 days after 1/2NX, and both were higher than levels of IGF-I extracted from contralateral kidneys 3 days after unilateral nephrectomy. Therefore, levels of IGF-I did not correlate with the extent of reduction of renal mass per se. We conclude that partial renal infarction provides a stimulus to enhance IGF-I expression. Increased renal IGF-I must be considered in the interpretation of findings originating from use of remnant kidney models of chronic renal failure.


Regeneration of Burnt Bridges on a DNA Catenane Walker.
DNA walkers are molecular machines that can move with high precision onthe nanoscale due to their structural and functional programmability. Despite recent advances in the field that allow exploring different energy sources, stimuli, and mechanisms of action for these nanomachines, the continuous operation and reusability of DNA walkers remains challenging because in most cases the steps, once taken by the walker, cannot be taken again. Herein we report the path regeneration of a burnt-bridges DNA catenane walker using RNase A. This walker uses a T7RNA polymerase that produces long RNA transcripts to hybridize to the path and move forward while the RNA remains hybridized to the path and blocks it for an additional walking cycle. We show that RNA degradation triggered by RNase A restores the path and returns the walker to the initial position. RNase inhibition restarts the function of the walker.


[A century of neurotransplantation in mammals].
The transplantation of neural tissue into the mammalian brain has been studied for a century. Although the experimental foundations of neurotransplantation were limited to basic biological issues, the progress made over the last decade in the use of foetal neurotransplants to replace interrupted neuronal pathways or to correct induced functional deficit of the central nervous system (C.N.S.), has opened a new field of research for repair of the damaged C.N.S. This review summarizes three major topics: (1) the major developments in the field of neurotransplantation since the first attempt in 1890, (2) the global field of application of grafting techniques of autologous, homologous and heterologous transplants to particular neuroaxonal systems in animal models (sensory, endocrine, motor, cognitive systems), (3) the specific applications of neurotransplantation to experimental forms of human neurological disorders in rodents and non human primates as a potential treatment for neurodegenerative diseases, and the future directions of neural grafting techniques (in vitro and transgenic techniques, artificial substrates) in the context of the scientific and the ethical problems which have been recently addressed.


Three-wave mixing mediated femtosecond pulse compression in β-barium borate.
Nonlinear pulse compression mediated by three-wave mixing is demonstrated for ultrashort Ti:sapphire pulses in a type II phase-matched β-barium borate (BBO) crystal using noncollinear geometry. 170 μJ pulses at 800 nm with a pulse duration of 74 fs are compressed at their sum frequency to 32 fs with 55 μJ of pulse energy. Experiments and computer simulations demonstrate the potential of sum-frequency pulse compression to match the group velocities of the interacting waves to crystals that were initially not considered in the context of nonlinear pulse compression.


Dissociation of pulse wave velocity and aortic wall stiffness in diabetic db/db mice: The influence of blood pressure.
Introduction: Vascular stiffness is a predictor of cardiovascular disease and pulse wave velocity (PWV) is the current standard for measuring in vivo vascular stiffness. Mean arterial pressure is the largest confounding variable to PWV; therefore, in this study we aimed to test the hypothesis that increased aortic PWV in type 2 diabetic mice is driven by increased blood pressure rather than vascular biomechanics. Methods and Results: Using a combination of in vivo PWV and ex vivo pressure myography, our data demonstrate no difference in ex vivo passive mechanics, including outer diameter, inner diameter, compliance (Db/db: 0.0094 ± 0.0018 mm2/mmHg vs. db/db: 0.0080 ± 0.0008 mm2/mmHg, p > 0.05 at 100 mmHg), and incremental modulus (Db/db: 801.52 ± 135.87 kPa vs. db/db: 838.12 ± 44.90 kPa, p > 0.05 at 100 mmHg), in normal versus diabetic 16 week old mice. We further report no difference in basal or active aorta biomechanics in normal versus diabetic 16 week old mice. Finally, we show here that the increase in diabetic in vivo aortic pulse wave velocity at baseline was completely abolished when measured at equivalent pharmacologically-modulated blood pressures, indicating that the elevated PWV was attributed to the concomitant increase in blood pressure at baseline, and therefore "stiffness." Conclusions: Together, these animal model data suggest an intimate regulation of blood pressure during collection of pulse wave velocity when determining in vivo vascular stiffness. These data further indicate caution should be exerted when interpreting elevated PWV as the pure marker of vascular stiffness.


Acceptability of Telelactation Services for Breastfeeding Support Among Black Parents: Semistructured Interview Study.
While breastfeeding rates have increased in the United States in recent years, racial and ethnic disparities persist. Telelactation may help reduce disparities by increasing access to lactation consultants, but there is limited research on acceptability among minoritized individuals. We aimed to explore experiences with telelactation among Black parents and identify strategies to make services more culturally appropriate. We selected 20 Black parents who were given access to telelactation services from an ongoing National Institutes of Health-funded randomized controlled trial (the Tele-MILC trial) to participate in semistructured interviews. Interviews addressed birth experiences, use and opinions about telelactation, comparison of telelactation to in-person lactation support, and recommendations to improve telelactation services. The thematic analysis was informed by a previously reported theoretical framework of acceptability and RAND Corporation's equity-centered model. Users appreciated the convenience of telelactation and reported that lactation consultants were knowledgeable and helpful. Participants wanted more options to engage with lactation consultants outside of video visits (eg, SMS text messaging and asynchronous resources). Users who had a lactation consultant of color mentioned that racial concordance improved the experience; however, few felt that racial concordance was needed for high-quality telelactation support. While Black parents in our sample found telelactation services to be acceptable, telelactation could not, in isolation, address the myriad barriers to long-duration breastfeeding. Several changes could be made to telelactation services to increase their use by minoritized populations.


Substrate specificity of thiamine pyrophosphate-dependent 2-oxo-acid decarboxylases in Saccharomyces cerevisiae.
Fusel alcohols are precursors and contributors to flavor and aroma compounds in fermented beverages, and some are under investigation as biofuels. The decarboxylation of 2-oxo acids is a key step in the Ehrlich pathway for fusel alcohol production. In Saccharomyces cerevisiae, five genes share sequence similarity with genes encoding thiamine pyrophosphate-dependent 2-oxo-acid decarboxylases (2ODCs). PDC1, PDC5, and PDC6 encode differentially regulated pyruvate decarboxylase isoenzymes; ARO10 encodes a 2-oxo-acid decarboxylase with broad substrate specificity, and THI3 has not yet been shown to encode an active decarboxylase. Despite the importance of fusel alcohol production in S. cerevisiae, the substrate specificities of these five 2ODCs have not been systematically compared. When the five 2ODCs were individually overexpressed in a pdc1Δ pdc5Δ pdc6Δ aro10Δ thi3Δ strain, only Pdc1, Pdc5, and Pdc6 catalyzed the decarboxylation of the linear-chain 2-oxo acids pyruvate, 2-oxo-butanoate, and 2-oxo-pentanoate in cell extracts. The presence of a Pdc isoenzyme was also required for the production of n-propanol and n-butanol in cultures grown on threonine and norvaline, respectively, as nitrogen sources. These results demonstrate the importance of pyruvate decarboxylases in the natural production of n-propanol and n-butanol by S. cerevisiae. No decarboxylation activity was found for Thi3 with any of the substrates tested. Only Aro10 and Pdc5 catalyzed the decarboxylation of the aromatic substrate phenylpyruvate, with Aro10 showing superior kinetic properties. Aro10, Pdc1, Pdc5, and Pdc6 exhibited activity with all branched-chain and sulfur-containing 2-oxo acids tested but with markedly different decarboxylation kinetics. The high affinity of Aro10 identified it as a key contributor to the production of branched-chain and sulfur-containing fusel alcohols.


Therapeutic options to manage bleeding in a dentist's office
This manuscript provides an overview of therapeutic options for the problem of bleeding in a dentist's office. Bleeding after tooth extraction is a very common finding in dental medicine and persistent blood in the mouth is obviously uncomfortable and sometimes terrifying for the patient. Most bleedings can be stopped simply with compression, in some cases a homeostatic therapy is necessary. For local compression, a swab with tranexamic acid is useful. If local compression is not sufficient, sutures are often an option. A very effective therapy would also be Tabotamp®, a local hemostypticum which is placed onto the bleeding and should increase the thrombocytic aggregation. In the worst case Floseal®, a human Thrombin, can be placed locally. It stops the bleeding very fast and sufficiently.


Structural insight into the activation mechanism of human pancreatic prophospholipase A2.
Pancreatic phospholipase A2 (phospholipase A2 group 1B, G1B) belongs to the superfamily of secreted phospholipase A2 (PLA2) enzymes. G1B has been proposed to be a potential target for diseases such as hypertension, obesity, and diabetes. Human pancreatic prophospholipase A2 (pro-hG1B) is activated by cleavage of the first seven-residue propeptide (phospholipase A2 propeptide, PROP). However, questions still remain on the mode of action for pro-hG1B. In this work, we expressed pro-hG1B in Pichia pastoris and determined the crystal structure at 1.55-A resolution. The x-ray structure demonstrates that pro-hG1B forms a trimer. In addition, PROP occupies the catalytic cavity and can be self-cleaved at 37 degrees C. A new membrane-bound surface and activation mechanism are proposed based on the trimeric model of pro-hG1B. We also propose a new autoproteolytic mechanism for pro-hG1B by the reaction triad Asp49-Arg0-Ser(-2) that is similar to the serine protease catalytic triad.


Low-Lying Tegmen and Surgical Outcomes Following the Middle Cranial Fossa Repair of Superior Canal Dehiscence.
To compare treatment response from the middle cranial fossa repair of superior canal dehiscence (SCD) between cases with and cases without low-lying tegmen (LLT). Cohort study. Single tertiary care institution. Two investigators independently reviewed preoperative high-resolution temporal bone computed tomography images and classified the ipsilateral tegmen as either "low-lying" or "control." Patients completed a symptom questionnaire and underwent audiometric testing pre- and post-operatively. Multivariable regression models assessed for symptomatic resolution and audiometric improvement following surgery with tegmen status as the primary predictor. Models controlled for patient age, sex, bilateral SCD disease, dehiscence location, prior ear surgery status, surgery duration, and follow-up duration. Among a total of 410 cases included, we identified 121 (29.5%) LLT cases. Accounting for all control measures, patients with LLT were significantly less likely to experience overall symptom improvement (adjusted odds ratio: 0.32, 95% confidence interval [CI]: 0.18-0.57, p < .001) and reported a significantly lower proportion of preoperative symptoms that resolved following surgery (adjusted β: -25.6%, 95% CI: -37.0% to -14.3%, p < .001). However, audiometric outcomes following surgery did not differ significantly between patients with and patients without LLT. This is the first investigation on the relationship between LLT and surgical outcomes following the middle fossa repair of SCD. Patients with LLT reported less favorable symptomatic response but exhibited a similar degree of audiometric improvement.


Molecular-dynamics studies of bending mechanical properties of empty and C60-filled carbon nanotubes under nanoindentation.
This paper utilizes molecular-dynamics simulations to investigate the mechanical characteristics of a suspended (10, 10) single-walled carbon nanotube (SWCNT) during atomic force microscopy (AFM) nanoindentation at different temperatures. Spontaneous topological transition of the Stone-Wales (SW) defects is clearly observed in the indentation process. The present results indicate that under AFM-bending deformation, the mechanical properties of the SWCNT, e.g., the bending strength, are dependent on the wrapping angle. In addition, it is also found that the radial dependence of the reduced formation energy of the SW defects is reasonably insensitive only for the small tubes. However, for tube diameters greater than 2.4 nm [corresponding to the (18, 18) CNT], the SW defects tend to be more radius sensitive. The results indicate that the bending strength decreases significantly with increasing temperature. This study also investigates the variation in the mechanical properties of the nanotube with the density of C60 encapsulated within the nanotube at various temperatures. It is found that, at lower temperatures, the bending strength of the C60-filled nanotube increases with C60 density. However, the reverse tendency is observed at higher temperatures. Finally, the "sharpest tip" phenomena between the probe and the tube wall and the elastic recovery of the nanotube during the retraction process are also investigated.


Role of murine leukemia virus nucleocapsid protein in virus assembly.
The retroviral nucleocapsid protein (NC) originates by cleavage of the Gag polyprotein. It is highly basic and contains one or two zinc fingers. Mutations in either the basic residues or the zinc fingers can affect several events of the virus life cycle. They frequently prevent the specific packaging of the viral RNA, affect reverse transcription, and impair virion assembly. In this work, we explore the role of NC in murine leukemia virus (MLV) particle assembly and release. A panel of NC mutants, including mutants of the zinc finger and of a basic region, as well as truncations of the NC domain of Gag, were studied. Several of these mutations dramatically reduce the release of virus particles. A mutant completely lacking the NC domain is apparently incapable of assembling into particles, although its Gag protein is still targeted to the plasma membrane. By electron microscopy on thin sections of virus-producing cells, we observed that some NC mutants exhibit various stages of budding defects at the plasma membrane and have aberrant particle morphology; electron micrographs of cells expressing some of these mutants are strikingly similar to those of cells expressing "late-domain" mutants. However, the defects of NC mutants with respect to virus release and infectivity could be complemented by an MLV lacking the p12 domain. Therefore, the functions of NC in virus budding and infectivity are completely distinct from viral late-domain function.


Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation.
An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.


Renal water channel expression in newborns: measurement of urinary excretion of aquaporin-2.
Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.


Collaborative design and use of an agency feedback form for student clinical practicum experience in community/public health nursing.
Evaluation of students in community and public health (C/PH) nursing clinical practica is a challenge, especially when preceptors are expected to evaluate students from different academic nursing programs. The need for a standardized student evaluation tool was identified during federally funded collaborative meetings held between C/PH academic and practice partners in Northeastern Wisconsin. This article focuses on the development and appraisal of the standardized Agency Feedback Form (AFF) for Student Practicum Experience in Community/Public Health Nursing, which was designed to meet the identified need. Four baccalaureate nursing programs implemented the AFF for 3 purposes: (1) to provide a consistent and easy evaluation form for preceptors to complete; (2) to communicate useful information about students' individual professional behaviors observed during practicum; and (3) to increase students' and preceptors' understanding of the population-based nursing interventions, using the Public Health Intervention Wheel. Future uses and implications of the AFF are also discussed.


[Central hemodynamics and prognostic significance of circulatory hyperdynamics after interventions for esophageal cancer].
Central hemodynamic parameters were studied by direct catheterization of the pulmonary artery in 70 patients with cancer of the esophagus and cardial portion of the stomach during the early postoperative period after extensive or extensive-combined interventions through the thoracoabdominal access. Analysis of the mean initial and intraoperative parameters at different stages of the operation showed no essential deviations from the norm. Studies of heart production at different stages showed that during transfer of patients from the operation room into intensive care ward, one-third of patients developed low ejection syndrome and another one-third hyperdynamic syndrome, while the mean values looked satisfactory. On days 3-5, circulatory hyperdynamia was detected in 60% patients, which was observed over the entire period of observation in 75% patients. It is noteworthy that polyorgan failure was 4-fold more often observed in patients with normal cardiac output than in those with the hyperdynamic syndrome. Probable causes of this phenomenon are discussed.


DIABETES MELLITUS IN THE SAND RAT INDUCED BY STANDARD LABORATORY DIETS.
During an attempt to establish a laboratory colony of the sand rat (Psammomys obesus) we found that this animal invariably became obese and developed severe diabetes mellitus when fed on commercial laboratory rat feed, but remained normal when fed on fresh vegetables only. The signs of diabetes included elevated blood glucose, excessive glucose and ketone bodies in the urine, and cataracts. The diabetic animals showed degeneration of the pancreatic insulin producing tissue (beta-cells).


Neonatal hemochromatosis: management, outcome, and prevention.
Neonatal hemochromatosis (NH) is a rare disorder but the most common cause of acute liver failure in neonates. NH is characterized by severe hepatic injury and iron overload and is associated with high perinatal mortality and morbidity rates. NH is often preceded by oligohydramnios and intrauterine growth restriction, suggesting an important impact of NH during fetal life. Stillbirth and prematurity are not uncommon. During the last decade, major discoveries on the etiology of NH have radically changed the management and outcome of this disease. NH is now regarded as an alloimmune disease and is, as such, often referred to as gestational alloimmune liver disease. Antenatal treatment with intravenous immunoglobulins starting at 14 weeks' gestation has been shown to prevent the development of NH in subsequent pregnancies. Postnatal treatment, previously based on the use of anti-oxidants and chelation therapy, has now successfully been replaced by exchange transfusions and intravenous immunoglobulins substitution. This review summarizes the latest discoveries on the etiology of NH and the new recommendations concerning its management and prevention.


Lung separation in the morbidly obese patient.
Lung separation techniques in the morbidly obese patient undergoing thoracic or esophageal surgery may be at risk of complications during airway management. Access to the airway in the obese patient can be a challenge because they have altered airway anatomy, including a short and redundant neck, limited neck extension and accumulation of fat deposition in the pharyngeal wall contributing to difficult laryngoscopy. Securing the airway is the first priority in these patients followed by appropriate techniques for lung separation with the use of a single-lumen endotracheal tube and a bronchial blocker or another alternative is with the use of a double-lumen endotracheal tube. This review is focused on the use of lung isolation devices in the obese patient. The recommendations are based upon scientific evidence, case reports or personal experience. Fiberoptic bronchoscopy must be used to place and confirm proper placement of a single-lumen endotracheal tube, bronchial blocker or double-lumen endotracheal tube.


CT-guided fine-needle aspiration and core needle biopsies of pulmonary lesions: a single-center experience with 750 biopsies in Japan.
CT-guided lung biopsy is a well-established diagnostic method for pulmonary lesions. The aim of our study was to evaluate the diagnostic outcomes and safety profile of conventional CT-guided lung biopsies. We retrospectively analyzed the results of CT-guided lung biopsies for 750 patients to determine the diagnostic accuracy, complication rates, and independent risk factors for diagnostic failure and severe pneumothorax. Diagnostic accuracy was 92.9%. Independent risk factors for diagnostic failure were malignant lesions (odds ratio [OR], 4.20; 95% CI, 1.66-14.1; p = 0.001), lesions in the lower lobe (OR, 2.01; 95% CI, 1.17-3.47; p = 0.011), lesions 2.0 cm or smaller (OR, 2.87; 95% CI, 1.59-5.48; p < 0.001), and the presence of pneumothorax during the procedure (OR, 2.18; 95% CI, 1.27-3.78; p = 0.004). Pneumothorax requiring drainage occurred in 7% of patients. Independent risk factors for pneumothorax requiring drainage were age of 73 years or older (OR, 2.19; 95% CI, 1.21-4.05; p = 0.009), the presence of emphysema (OR, 4.29; 95% CI, 2.05-8.82; p < 0.001), benign lesions (OR, 2.33; 95% CI, 1.20-4.40; p = 0.012), supine positioning of the patient (OR, 2.61; 95% CI, 1.44-4.84; p = 0.001), and length from the pleura to the lesion of 1.5 cm or greater (OR, 3.08; 95% CI, 1.63-6.17; p < 0.001). CT-guided lung biopsy has a high diagnostic accuracy. Complication rates were acceptable and comparable to those of previous studies.


General practice in Gloucestershire, Avon and Somerset: explaining variations in standards.
Variations in standards are found in all health services. The method and amount of funding are thought to be important reasons for these variations. A cross sectional survey of all general practices in three counties in south west England was undertaken in order to explain variations in the level of development. A development score for each practice was calculated. There was wide variation in standards as described by the level of development. Multiple regression analysis showed that being a training practice, having a practice manager, the partners having a younger mean age, a larger total number of patients registered with the practice and a lower Jarman underprivileged area score were all independently related to a higher level of practice development. In addition, the responsible family health services authority was also related to the level of development. A combination of professional factors such as the decision to become a training practice, environmental factors such as the family health services authority or the underprivileged area score and economic factors reflected in the total list size determine the level of practice development. The most easily corrected factor is the employment of a practice manager. It is suggested that differences in standards in general practice may be increased rather than decreased by the fundholding scheme.


Molecular crowding and RNA catalysis.
RNA enzymes or ribozymes catalyze some of the most important reactions in biology and are thought to have played a central role in the origin and evolution of life on earth. Catalytic function in RNA has evolved in crowded cellular environments that are different from dilute solutions in which most in vitro assays are performed. The presence of molecules such as amino acids, polypeptides, alcohols, and sugars in the cell introduces forces that modify the kinetics and thermodynamics of ribozyme-catalyzed reactions. Synthetic molecules are routinely used in in vitro studies to better approximate the properties of biomolecules under in vivo conditions. This review discusses the various forces that operate within simulated crowded solutions in the context of RNA structure, folding, and catalysis. It also explores ideas about how crowding could have been beneficial to the evolution of functional RNAs and the development of primitive cellular systems in a prebiotic milieu.


Che-1 inhibits oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis associated with inhibition of the p53-mediated proapoptotic signaling pathway.
Accumulating evidence suggests that Che-1 is a strong antiapoptotic protein and can protect cells against various insults. However, whether Che-1 is involved in the protection of neurons against cerebral ischemia/reperfusion injury remains unclear. In this study, we aimed to investigate the potential role of Che-1 in regulating cerebral ischemia/reperfusion injury-induced neuronal injury using the oxygen-glucose deprivation and reoxygenation (OGD/R) model in vitro. We found that Che-1 expression was induced in neurons following OGD/R treatment. Functional experiments showed that Che-1 knockdown aggravated OGD/R-induced neuronal apoptosis. In contrast, Che-1 overexpression exerted a protective effect against OGD/R-induced neuronal apoptosis. Moreover, our results showed that the protective effect of Che-1 was associated with the inhibition of p53-mediated proapoptotic genes, including Puma, Noxa, and Bax. In addition, we showed that Che-1 impeded the transcript activity of p53 toward apoptosis. Taken together, our results indicate that Che-1 alleviates OGD/R-induced neuronal apoptosis in-vitro through inhibition of p53-mediated proapoptotic signaling. Our study suggests that Che-1 may serve as a potential therapeutic target for the treatment of cerebral ischemic/reperfusion injury in vivo.


Influence of ion size and charge on osmosis.
Osmosis is fundamental to many processes, such as in the function of biological cells and in industrial desalination to obtain clean drinking water. The choice of solute in industrial applications of osmosis is highly important in maximizing efficiency and minimizing costs. The macroscale process of osmosis originates from the nanoscale properties of the solvent, and therefore an understanding of the mechanisms of how these properties determine osmotic strength can be highly useful. For this reason, we have undertaken molecular dynamics simulations to systematically study the influence of ion size and charge on the strength of osmosis of water through carbon nanotube membranes. Our results show that strong osmosis occurs under optimum conditions of ion placement near the region of high water density near the membrane wall and of maintenance of a strong water hydration shell around the ions. The results in turn allow greater insight into the origin of the strong osmotic strength of real ions such as NaCl. Finally, in terms of practical simulation, we highlight the importance of avoiding size effects that can occur if the simulation cell is too small.


Surveillance of Antibiotic Resistance of Maltose-Negative Staphylococcus aureus in South African Dairy Herds.
Antibiotic resistance has been reported since the 1940s in both human and veterinary medicine. Many years of monitoring milk samples in South Africa led to identification of a novel maltose-negative Staphylococcus aureus (S. aureus) strain, which appears to be an emerging pathogen. In this study, the susceptibility of this strain to antibiotics was evaluated over time, during diverse seasons in various provinces and according to somatic cell count (SCC) categories. A data set of 271 maltose-negative S. aureus isolates, from milk samples of 117 dairy herds, was examined using the disk diffusion method, between 2010 and 2017. This study also compared the susceptibility testing of 57 maltose-negative and 57 maltose-positive S. aureus isolated from 38 farms, from three provinces using minimum inhibitory concentration (MIC). The MIC results for the maltose-negative S. aureus isolates showed highest resistance to ampicillin (100%) and penicillin (47.4) and lowest resistance (1.8%) to azithromycin, ciprofloxacin and erythromycin. The maltose-negative S. aureus isolates showed overall significantly increased antibiotic resistance compared to the maltose-positive strains, as well as multidrug resistance. Producers and veterinarians should consider probability of cure of such organisms (seemingly non-chronic) when adapting management and treatment, preventing unnecessary culling.


Teratomas, neoplasia and differentiation: a biological overview. I. The natural history of teratomas.
In this paper I have attempted to outline the natural history of spontaneously occurring teratomas and associated tumours, but without introducing any preconceptions or assumptions as to their histogenesis or mechanisms of internal differentiation. The justification for this omission is that there is presently no direct evidence in respect of either process in human tumours of this type, with the exception of recent work by LINDER et al. (1975a, b). The various histopathological classifications of teratoid lesions have not been discussed in detail either, because for the most part they have been evolved to serve a specific prognostic purpose on either an empirical basis or on certain histogenetic assumptions. In either case there is an inevitable tendency to emphasize extremes of morphological appearance at the expense of possible continuities of structure and behaviour across the spectrum of teratoid lesions. The purpose of this paper, on the contrary, has been to discern features common to these tumours whenever and wherever they occur. Thus, human teratomas are uniquely puritissular lesions composed, potentially at least, of virtually every recognizable (and probably some as yet unrecognizable), type of embryonic, foetal and adult cell and tissue, together with, in some cases, frankly malignant cells of no obvious derivation or differentiation. In spite of the occasional appearance of structures resembling pre-somite embryos (embryoid bodies), there is no compelling evidence that human teratomatous histogenesis recapitulates embryogenesis in any strict fashion. Histologically, the overwhelming impression is of a more or less random association of cells and tissues at different stages of development and differentiation that proceed up to but not beyond organogenesis. Such teratomas are found at a number of well-defined sites, of which the sacrococcyx is the most prominent in infancy and the gonads during adult life. Both gonadal and extragonadal sites are also associated with apparently homogeneous neoplasms containing cells with features reminiscent of early stages of germinal differentiation which evoke, in many cases, a marked stromal and lymphocytic response, the so-called germinomas. In 'mixed' tumours, which are recognized in an increasing proportion of cases, there is karyological evidence of a conjoint rather than separate origin of teratomatous and germinomatous elements in at least some tumours, challenging a long held belief in their invariably separate character (e.g. HALLEY, 1963).


Engineering cobalt oxide by interfaces and pore architectures for enhanced electrocatalytic performance for overall water splitting.
The development of efficient electrocatalysts for overall water splitting is important for future renewable energy systems. Herein, macroporous CoO covered by Co/N-doped graphitic carbon nanosheet arrays (mac-CoO@Co/NGC NSAs) were constructed by engineering a mesoporous CoO nanowire (mes-CoO NWAs) core with highly conductive Co nanoparticles coated by a N-doped graphitic carbon (Co/NGC) shell. The in situ derived Co/NGC shell not only introduces electrocatalytic active sites for the hydrogen evolution reaction (HER) but also promotes the oxygen evolution reaction (OER) through the strong interaction between the CoO core and the Co/NGC shell. Moreover, the highly conductive Co/NGC shell crosslinks the isolated mesoporous CoO nanowires into a nanosheet rich in macropores, ensuring effective electron and mass transfer. Furthermore, the chemically stable N-doped graphitic carbon layer and physically stable hierarchical nanosheet arrays ensure the stability of the catalyst. Owing to the desirable interfaces and pore architecture, the as-prepared mac-CoO@Co/NGC NSAs can serve as highly effective, binder-free electrocatalysts for overall water splitting with a stable cell voltage of 1.62 V at 10 mA cm-2 for 35 h.


Copper-catalyzed synthesis of allenylboronic acids. Access to sterically encumbered homopropargylic alcohols and amines by propargylboration.
Tri- and tetrasubstituted allenylboronic acids were prepared via a new versatile copper-catalyzed methodology. The densely functionalized allenylboronic acids readily undergo propargylboration reactions with ketones and imines without any additives. Catalytic asymmetric propargylborylation of ketones is demonstrated with high stereoselectivity allowing for the synthesis of highly enantioenriched tertiary homopropargyl alcohols. The reaction is suitable for kinetic resolution of racemic allenylboronic acids affording alkynes with adjacent quaternary stereocenters.


Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids.
Ten (3 percent) of 287 patients receiving combination chemotherapy developed severe bleomycin-induced pneumonitis. The course and the response to therapy in these patients are summarized in this report. The dose of bleomycin received varied from 136 to 588 units, with toxic effects occurring in six patients who had received less than 200 units. Dyspnea and dry cough were the presenting symptoms in nine patients; one was asymptomatic. Roentgenograms were abnormal in nine cases, with five showing bilateral infiltrates. Four patients had asymmetric abnormalities, with radiographic involvement of only a single lung in two of these. Pulmonary function tests were abnormal, with a decreased diffusing capacity. Seven patients were treated with corticosteroid therapy, and significant clinical and radiographic improvement was noted; however, pulmonary function tests remained abnormal and could not be used to monitor the response. Prolonged therapy with corticosteroids was required over many months to maintain improvement. Tapering of the steroid dosage led to recurrence of clinical symptoms and radiographic infiltrates in five patients. Mortality was 60 percent, with three early deaths in untreated patients and three late deaths which occurred 12 to 15 months after diagnosis. In this study, patients with severe bleomycin-induced pneumonitis had symptomatic improvement and roentgenographic clearing following corticosteroid therapy.


Classification and survival rate of patients with serous cystadenocarcinoma of the ovaries.
The comparative evaluation of two stage classifications including USSR Ministry of Health stage classification and TNM system was performed on the base of studies of the end results of 419 patients with serous cystadenocarcinoma of the ovaries. It has been established that TNM system is of a greater importance in establishing more accurate prognosis than the stage classification of the Ministry of Health. In TNM system four variants of the degree of extension correspond to each stage that allows to evaluate not only the extent of the primary tumor that also of the metastatic spread. The achieved results point to the superiority of the TNM system and serve as a base for transition to the TNM system in the classification of ovarian carcinoma.


Matrix-implanted laser desorption/ionization mass spectrometry.
The implantation of low-velocity massive gold clusters is shown to be a method of choice for homogeneous incorporation of a metallic matrix into the near-surface region of a solid biopolymer for subsequent laser desorption/ionization (LDI) MS analysis. Matrix implanted (MI)LDI spectra from cluster-implanted pure test peptide or tissue exhibit molecular ion peaks similar to those observed by matrix-assisted LDI. Moreover, the ion emission is very reproducible from any spot on the surface of these test samples. MILDI promises to be a powerful technique for mass spectrometric analysis of native biological samples as demonstrated by the first results on rat brain tissues.


Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency.
Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.


Cyclic AMP regulation of calcium mobilization and amylase release from isolated permeabilized rat parotid cells.
This study examined the mechanistic basis of the synergistic interaction between the cyclic AMP (cAMP) and phosphoinositide pathways in salivary amylase secretion. cAMP produced a concentration-dependent increase in Ca++ mobilization from saponin-permeabilized rat parotid acinar cells. A threshold concentration of cAMP (50 microM) significantly increased the peak Ca(++)-releasing activity of submaximal concentrations of inositol 1,4,5-trisphosphate (IP3) but did not augment the Ca++ mobilization induced by a maximal stimulating concentration of IP3 (30 microM). A maximal stimulating concentration of cAMP (500 microM) failed to modify the Ca++ releasing action of IP3. IP3-induced Ca++ release was also augmented by catalytic subunit of cAMP-dependent protein kinase. A specific protein kinase inhibitor reversed this effect. The cAMP-induced Ca++ release was blocked by ryanodine but not by heparin, by contrast with the IP3-induced Ca++ release. Thapsigargin only partially depressed the cAMP response but completely abolished the IP3 response. The amylase release elicited by fixed concentrations of Ca++ was not further enhanced by either cAMP or forskolin. Thus, unlike diacylglycerol, which decreases the Ca++ requirement for secretion by inducing activation of protein kinase C, cAMP appears to mediate salivary amylase secretion by regulating the sensitivity of parotid cells to the Ca++ mobilizing action of IP3. In addition, cAMP possesses a second action, i.e., directly eliciting Ca++ mobilization from an IP3-insensitive pool.


Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times.
The aim of the study is to investigate whether platelet activity is increased by hyperprolactinemia during pregnancy as reflected by beta-thromboglobulin level. Forty-eight healthy, pregnant, and 30 healthy, non-pregnant women were investigated with respect to platelet count, collagen/ADP and collagen/epinephrine closure times, beta-thromboglobulin and prolactin levels. The comparison of the variables between the two groups was made by Mann-Whitney U test. The correlation analyses were performed by Spearman's rank correlation test. Our results revealed that platelet counts, collagen/ADP and collagen/epinephrine closure times and beta-thromboglobulin showed no statistically significant differences between pregnant and non-pregnant women. We found no significant correlation between prolactin and collagen/ADP closure time (r = 0.175), between prolactin and collagen/epinephrine closure time (r = -0.112) and between prolactin and beta-thromboglobulin (r = 0.220) in pregnant women. Our findings suggest that platelet activity is comparable during pregnant and non-pregnant states and there is no significant effect of prolactin on platelet function in vivo as reflected by beta-thromboglobulin level.


Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) in a temperate re-connected floodplain.
The relative magnitudes of, and factors controlling, denitrification and dissimilatory nitrate reduction to ammonium (DNRA) were measured in the soil of a re-connected temperate floodplain divided into four different land management zones (grazing grassland, hay meadow, fritillary meadow and a buffer zone). Soil samples were collected from each zone to measure their respective potentials for nitrate attenuation using 15N both at the surface and at depth in the soil column and additional samples were collected to measure the lability of the organic carbon. Denitrification capacity ranged between 0.4 and 4.2 (μmol N g(-1) dry soil d(-1)) across the floodplain topsoil and DNRA capacity was an order of magnitude lower (0.01-0.71 μmol N g(-1) d(-1)). Land management practice had a significant effect on denitrification but no significant effects were apparent for DNRA. In this nitrogen-rich landscape, spatial heterogeneity in denitrification was explained by differences in lability and the magnitude of organic carbon associated with different management practices (mowing and grazing). The lability of organic carbon was significantly higher in grazing grassland in comparison to other ungrazed areas of the floodplain, and consequently denitrification capacity was also highest in this area. Our results indicate that bacteria capable of DNRA do survive in frequently flooded riparian zones, and to a limited extent, compete with denitrification for nitrate, acting to retain and recycle nitrogen in the floodplain. Exponential declines in both denitrification and DNRA capacity with depth in the floodplain soils of a hay meadow and buffer zone were controlled primarily by the organic carbon content of the soils. Furthermore, grazing could be employed in re-connected, temperate floodplains to enhance the potential for nitrate removal from floodwaters via denitrification.


Factors That Influence the Judgment of Oral Management Necessity in Preoperative Oral Screening.
Oral management during the perioperative period is important to prevent the development of postoperative complications. However, there are no unified systems to examine the oral status of patients and very few studies have focused on preoperative oral screening. In this study, we examined the oral status of patients who underwent oral screening at a University Hospital. A total of 1173 patients who underwent oral screening for perioperative management from April 2020 to July 2021 were enrolled. The subjects' medical data were retrospectively extracted from the dental records, and finally, the data of 1081 patients aged ≥20 years were analyzed. Oral screening based on seven categories was performed by dentists or dental hygienists. Our cumulative results determined whether patients required oral management during the perioperative period. "Poor oral hygiene" was the most frequent category (24%) of all oral categories examined. Logistic analysis revealed that tooth mobility had the highest odds ratio (21.476; 95% confidence interval: 11.462-40.239; p < 0.001) for oral management necessity during the perioperative period. Our study suggests that poor oral hygiene is most frequently observed in preoperative oral screening. Moreover, tooth mobility in preoperative oral screening may influence the judgment of oral management necessity during the perioperative period.


Densified biomass can cost-effectively mitigate greenhouse gas emissions and address energy security in thermal applications.
Regional supplies of biomass are currently being evaluated as feedstocks in energy applications to meet renewable portfolio (RPS) and low carbon fuel standards. We investigate the life cycle greenhouse gas (GHG) emissions and associated abatement costs resulting from using densified switchgrass for thermal and electrical energy. In contrast to the large and positive abatement costs for using biomass in electricity generation ($149/Mg CO(2)e) due to the low cost of coal and high feedstock and power plant operation costs, abatement costs for replacing fuel oil with biomass in thermal applications are large and negative (-$52 to -$92/Mg CO(2)e), resulting in cost savings. Replacing fuel oil with biomass in thermal applications results in least cost reductions compared to replacing coal in electricity generation, an alternative that has gained attention due to RPS legislation and the centralized production model most often considered in U.S. policy. Our estimates indicate a more than doubling of liquid fuel displacement when switchgrass is substituted for fuel oil as opposed to gasoline, suggesting that, in certain U.S. locations, such as the northeast, densified biomass would help to significantly decarbonize energy supply with regionally sourced feedstock, while also reducing imported oil. On the basis of supply projections from the recently released Billion Ton Report, there will be enough sustainably harvested biomass available in the northeast by 2022 to offset the entirety of heating oil demand in the same region. This will save NE consumers between $2.3 and $3.9 billion annually. Diverting the same resource to electricity generation would cost the region $7.7 billion per year. While there is great need for finding low carbon substitutes for coal power and liquid transportation fuels in the U.S., we argue that in certain regions it makes cost- (and GHG mitigation-) effective sense to phase out liquid heating fuels with locally produced biomass first.


Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H.
In 2005 the commonality of sarcotubular myopathy (STM) and limb girdle muscular dystrophy type 2H (LGMD2H) was demonstrated, as both are caused by the p D487N missense mutation in TRIM32 originally found in the Manitoba Hutterite population. Recently, three novel homozygous TRIM32 mutations have been described in LGMD patients. Here we describe a three generation Swedish family clinically presenting with limb girdle muscular weakness and histological features of a microvacuolar myopathy. The two index patients were compound heterozygotes for a frameshift mutation in TRIM32 (c.1560delC ) and a 30 kb intragenic deletion, encompassing parts of intron 1 and the entire exon 2 of TRIM32. In these patients, no full-length or truncated TRIM32 could be detected. Interestingly, heterozygous family members carrying only one mutation showed mild clinical symptoms and vacuolar changes in muscle. In our family, the phenotype encompasses additionally a mild demyelinating polyneuropathic syndrome. Thus STM and LGMD2H are the result of loss of function mutations that can be either deletions or missense mutations.


A qualitative exploration of Thai alcohol policy in regulating availability and access.
Despite abundant alcohol control regulations and measures in Thailand, prevalence of alcohol consumption has been relatively steady for the past decade and alcohol-related harm remains high. This study aims to explore, through the perspectives of key public health stakeholders, the current performance of regulations controlling alcohol availability and access, and the future directions for the implementation of Thai alcohol policy. Semi-structured interviews were conducted with public health stakeholders from three sectors; the government, academia and civil society. Their perceptions about the current alcohol situation, gaps in the current policies, and future directions of alcohol policy were discussed. Audio data were transcribed verbatim, systematically coded and analysed. The three key concerning issues were physical availability, economic availability and commercial access, which referred to outlet density, taxation and pricing, and compliance to stipulated regulations, respectively. First, Thailand failed to control the number of alcohol outlets. The availability problem was exacerbated by the increased numbers of liquor licences issued, without delineating the need for the outlets. Second, alcohol tax rates, albeit occasionally adjusted, are disproportionate to the economic dynamic, and there is yet a minimum pricing. Finally, compliance to age and time restrictions was challenging. The lack of robustness of enforcement and disintegration of government agencies in regulating availability and access hampers effectiveness of alcohol policy. Comprehensive regulations for the control of availability of and access to alcohol are required to strengthen alcohol policy. Consistent monitoring and surveillance of the compliances are recommended to prevent significant effects of the regulations diminish over time.


Restricted immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia.
Between 10% and 25% of chronic lymphocytic leukemia (CLL) patients have episodes of autoimmune hemolytic anemia (AIHA) during the course of their disease. The anti-erythrocyte autoantibodies in most cases are polyclonal and express a different heavy chain isotype than the malignant clone, indicating that they are secreted by normal autoreactive B lymphocytes. To further investigate the pathogenesis of the AIHA in CLL, we analyzed the lg heavy (H) chain variable region genes expressed by leukemic cells from CLL patients with and without AIHA. Two VH genes were preferentially expressed by the leukemic cells in the CLL cases with AIHA and were present in 9 of the 12 investigated cases. The 51p1/DP-10 gene was expressed in 5 of these cases and was absent in the control group of 12 consecutive CLL cases without AIHA, whereas the DP-50 gene was present in 4 CLL-AIHA cases and only once in the control CLL group. A strikingly similar H-chain CDR3 region that contained a single reading frame of the DXP4 DH gene segment, and N-encoded proline at the DH/JH boundary, and a tyrosine-rich region encoded by the JH6 gene segment was observed in four CLL-AIHA cases. The preferential expression of two VH gene segments and a particular CDR3 region by the leukemic cells of patients with AIHA suggests that the antibodies produced by the CLL cells are directly involved in the pathogenesis of the hemolytic anemia.


Cardiac function and histological changes after non-dynamic cardiomyoplasty and preliminary study of dynamic cardiomyoplasty.
By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4 +/- 11.7% in Group I (3 weeks after operation), and 78.4 +/- 11.6% atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P < 0.05), but the difference between two groups was non- significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-resistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.


Determinants of major cardiovascular risk factors among participants of the South Carolina WISEWOMAN program, 2009-2012.
Cardiovascular disease (CVD) is the leading cause of death among US women, accounting for 25% of all deaths in this population. Approximately 65% of these deaths occur in asymptomatic women. Hypertension, hypercholesterolemia, and diabetes mellitus (diabetes) are major risk factors for CVD and can be treated effectively if identified at an early stage. Data were available from 3,572 uninsured first-time female participants aged 40 to 65 years, referred by their health professional to the South Carolina Well-Integrated Screening and Evaluation for Women Across the Nation (SC WISEWOMAN), 2009-2012. All women completed a structured health-risk and behavior questionnaire. Anthropometric measures were recorded and data on clinical risk-factors were collected. Prevalence-ratios (PRs) were obtained by predictive multivariable log-linear modeling. The prevalence of risk factors was 34.7% for uncontrolled hypertension, 9.3% for hypercholesterolemia, and 21% for diabetes. Prevalence of untreated hypertension was 15.6%; hypercholesterolemia, 8%; and diabetes, 4%. The greatest significant predictor of hypercholesterolemia was hypertension (PR = 4.37) and vice versa (PR = 2.39). The greatest significant predictors of diabetes were obesity (PR = 2.23), family history of diabetes (PR = 2.02), and hypercholesterolemia (PR = 1.85). Being obese (PR = 1.36), overweight (PR = 1.23), aged 60 years or more (PR = 1.26), and black (PR = 1.14) were significant predictors of having at least one CVD risk factor. Being black (PR = 1.09) was the only significant predictor of having comorbid conditions. Prevalence of uncontrolled CVD risk factors was high among participants in the SC WISEWOMAN program. These findings confirm that the program is reaching high-risk women who are in need of interventions to reduce their risk for CVD through lifestyle changes.


Determinants of high-grade anal intraepithelial lesions in HIV-positive MSM.
To assess determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive men who have sex with men (MSM), a population at high-risk of HPV-related anal cancer. APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged at least 35 years in six centres across France. At baseline, participants underwent high-resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression. Baseline hHSIL prevalence was 10.4% and did not differ significantly by age, sexual behaviour or HIV/immunodeficiency markers. hHSIL prevalence was significantly elevated in participants who smoked (ORadj = 2.6, 95% CI 1.3-5.5) or who, in concurrent anal swabs, had ASCUS/LSIL (3.6, 95% CI 1.4-9.3) or ASC-H/HSIL (22.2, 95% CI 6.8-72.6) cytologic abnormalities, p16/Ki67 dual positivity (3.4, 95% CI 1.5-7.5), or non-HPV16 HR (13.0, 95% CI 1.7-102), but most notably, HPV16 (46.3, 95% CI 6.1-355) infection. Previous diagnosis of low-grade (2.3, 95% CI 1.0-5.4) or high-grade (3.8, 95% CI 1.5-9.9) anal lesion also conveyed higher hHSIL risk. After controlling for patient-specific determinants, there remained significant centre-specific effects, most clearly in higher risk groups (HPV16-positive participants: 31.3% hHSIL in centres A-D versus 5.1% in centres E and F, P < 0.01). Anal cytology and HPV16 infection are potentially useful determinants of hHSIL risk in HIV-positive MSM, but HIV/immunodeficiency-related variables appear not to be. Controlling for patient-specific hHSIL determinants highlights variability in HRA practice across diverse clinical settings and the need for better standardization of this difficult procedure.


Osteoarthritis-Related Knee Pain Treated With Genicular Artery Embolization: A Systematic Review and Meta-analysis.
Genicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee osteoarthritis (OA). To evaluate the current evidence on the effectiveness and safety of GAE for OA-related knee pain. Systematic review; Level of evidence, 4. A systematic literature search was conducted in the PubMed, Web of Science, EMBASE, and Scopus databases to identify studies related to knee OA treated with GAE. Treatment agents were categorized as Embozene, imipenem/cilastatin, resorbable microspheres, and polyvinyl alcohol. The main outcomes were the mean difference (MD) in pre- and postembolization pain based on the visual analog scale (VAS) or the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores as well as changes in the need for pain medication. Random- and fixed-effects models were applied for data analysis. Of 379 initially inspected publications, 11 (N = 225 patients; 268 knees) were included in the final review. The quality of the studies was fair in 8 and poor in 3-categorized according to the National Institutes of Health quality assessment tool. Overall, 119, 72, 13, and 21 patients were treated with imipenem/cilastatin, Embozene, resorbable microspheres, and polyvinyl alcohol, respectively. Symptomatic improvement was reported in all studies. The pooled effect size, characterized by MD, showed a significant improvement in the VAS and WOMAC pain scores, with better functional status after GAE. Pre- versus postembolization MDs in VAS scores ranged from 32 within the first week to 58 after a 2-year follow-up (equivalent to 54% and 80% improvement, respectively). There was a similar trend in the overall WOMAC scores, with MDs ranging from 28.4 to 36.8 (about 58% and 85% improvement, respectively). GAE resulted in a decreased need for pain medication for knee OA, with a 27%, 65%, and 73% decline in the number of patients who used opioids, nonsteroidal anti-inflammatory drugs, and intra-articular hyaluronic acid injection, respectively (P < .00001 for all). No significant difference between embolic agents was seen with regard to post-GAE pain reduction. No severe or life-threatening complications were reported. OA treated by GAE using different embolic particles can be considered generally safe, with good efficacy and no reported serious complications.


Cationic double chained metallosurfactants: synthesis, aggregation, cytotoxicity, antimicrobial activity and their impact on the structure of bovine serum albumin.
Bovine serum albumin (BSA) is one of the most copious and significant blood proteins with dynamic structure. The understanding of the structural functionality of BSA and its interaction with metal ions is desired for various biological functions. Herein, three different metallosurfactants containing different transition metals and the same hydrophobic tail were engaged to investigate the structural transition of BSA. The metallosurfactants have been prepared by a combination of metal ions (M = Fe, Co and Ni) with cetylpyridinium chloride surfactant via the ligand insertion method and were characterized by elemental, FTIR, 1H-NMR, and thermogravimetric analysis (TGA). The obtained results reveal that insertion of a metal ion perturbs the aggregation behavior of the surfactant. Incorporation of a metal-ion has been found to decrease the CMC value of the surfactant, which has been supported by conductivity, surface tension and small angle X-ray scattering (SAXS). These metallosurfactants were employed to study the interaction and binding mechanism of BSA under physiological conditions. SDS-PAGE analysis points out a weak effect of metallosurfactants on the primary structure of BSA, whereas CD spectra implied a significant change in secondary structure with the decreased α-helical content of BSA. Fluorescence spectroscopy indicates the effect of metallosurfactants on the tertiary structure of BSA, whereas absorption spectra demonstrated static quenching with a blue shift in the presence of metallosurfactants. Moreover, unfolding of BSA in the presence of metallosurfactants has also been confirmed by SAXS studies. The overall results indicate that insertion of the metal ion into the framework of the surfactant structure enhances its protein binding/folding/unfolding abilities, which would be helpful in clinical as well as in life sciences.


Long Noncoding RNAs in the Prediction of Survival of Patients with Digestive Cancers.
Long noncoding RNAs have been known to be involved in various cancers. This study aimed to find a long noncoding RNA signature to predict the prognostic risk of patients with digestive cancers, including esophageal carcinoma, stomach adenocarcinoma, liver hepatocellular carcinoma, and pancreatic adenocarcinoma. After screening differentially expressed long noncoding RNAs in 4 digestive cancers from The Cancer Genome Atlas database, the prognostic significance of the above differentially expressed long noncoding RNAs was evaluated by Kaplan-Meier analysis. Target genes of the corresponding differentially expressed long noncoding RNAs were predicted by StarBase. We performed bioinformatics methods, including gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, to explore the role and molecular mechanisms of differentially expressed long noncoding RNAs and predicted target genes in tumor progression. A total of 4 differentially expressed long noncoding RNAs (AC093895.1, CASC9, LINC01980, and HOXC-AS2) with a significant prognostic value were identified. Moreover, 6 target genes were obtained. Also, functional enrichment analysis showed that these 4 DELs were mainly related to the regulation of mRNA metabolic process, regulation of RNA stability, mRNA binding, RNA localization, and spliceosome. The prognostic differentially expressed long noncoding RNAs and target genes in the digestive cancers were obtained, which may provide a novel direction for treatment and prognosis improvement of digestive cancers.


Event-based prospective remembering in a virtual world.
Most laboratory-based prospective memory (PM) paradigms pose problems that are very different from those encountered in the real world. Several PM studies have reported conflicting results when comparing laboratory- with naturalistic-based studies (e.g., Bailey, Henry, Rendell, Phillips, & Kliegel, 2010 ). One key contrast is that for the former, how and when the PM cue is encountered typically is determined by the experimenter, whereas in the latter case, cue availability is determined by participant actions. However, participant-driven access to the cue has not been examined in laboratory studies focused on healthy young adults, and its relationship with planned intentions is poorly understood. Here we report a study of PM performance in a controlled, laboratory setting, but with participant-driven actions leading to the availability of the PM cue. This uses a novel PM methodology based upon analysis of participant movements as they attempted a series of errands in a large virtual building on the computer screen. A PM failure was identified as a situation in which a participant entered and exited the "cue" area outside an errand related room without performing the required errand whilst still successfully remembering that errand post test. Additional individual difference measures assessed retrospective and working memory capacity, planning ability and PM. Multiple regression analysis showed that the independent measures of verbal working memory span, planning ability, and PM were significant predictors of PM failure. Correlational analyses with measures of planning suggest that sticking with an original plan (good or bad) is related to better overall PM performance.


Long-Term Changes in the Distributions of Larval and Adult Fish in the Northeast U.S. Shelf Ecosystem.
Many studies have documented long-term changes in adult marine fish distributions and linked these changes to climate change and multi-decadal climate variability. Most marine fish, however, have complex life histories with morphologically distinct stages, which use different habitats. Shifts in distribution of one stage may affect the connectivity between life stages and thereby impact population processes including spawning and recruitment. Specifically, many marine fish species have a planktonic larval stage, which lasts from weeks to months. We compared the spatial distribution and seasonal occurrence of larval fish in the Northeast U.S. Shelf Ecosystem to test whether spatial and temporal distributions changed between two decades. Two large-scale ichthyoplankton programs sampled using similar methods and spatial domain each decade. Adult distributions from a long-term bottom trawl survey over the same time period and spatial area were also analyzed using the same analytical framework to compare changes in larval and adult distributions between the two decades. Changes in spatial distribution of larvae occurred for 43% of taxa, with shifts predominately northward (i.e., along-shelf). Timing of larval occurrence shifted for 49% of the larval taxa, with shifts evenly split between occurring earlier and later in the season. Where both larvae and adults of the same species were analyzed, 48% exhibited different shifts between larval and adult stages. Overall, these results demonstrate that larval fish distributions are changing in the ecosystem. The spatial changes are largely consistent with expectations from a changing climate. The temporal changes are more complex, indicating we need a better understanding of reproductive timing of fishes in the ecosystem. These changes may impact population productivity through changes in life history connectivity and recruitment, and add to the accumulating evidence for changes in the Northeast U.S. Shelf Ecosystem with potential to impact fisheries and other ecosystem services.


Formation peculiarities of radiation-induced aberrations of chromosomes in human cells under the modifying influence of chemical agents (comparative aspects).
The study objective was to determine and provide a comparative analysis of frequency and spectrum of the induced aberrations of chromosomes in culture of the human peripheral blood lymphocytes under the combined impact of radiation, co-mutagen, and chemical mutagen. Culture of human peripheral blood lymphocytes and cytogenetic methods have been used. A co-mutagenic effect of the drug verapamil was established under the testing γ-irradiation of human peripheral blood lymphocytes in the dose range of 0.3-2.0 Gy at the expense of increased frequency of chromosomal aberrations (dicentrics). The combined effect of γ-irradiation and S-Nitrosoglutathione is directed on the induction and storage of chemical markers of exposure - the chromatid-type aberrations. A co-mutagenic effect of verapamil under the low-dose γ-irradiation as a 2-fold increase of the chromosome-type aberrations (radiation markers) incidence was revealed at a chromosomal level in human peripheral blood lymphocytes. Phenomenon of synergism of low-dose γ-irradiation and mutagen S-Nitrosoglutathione as a ~3-fold increased frequency of chromatid-type aberrations (chemical markers) was detected compared to the sole radiation effect.


Different strategies of differential display: areas of application.
The main goal of this review is to provide some guide-lines for choosing a proper method when searching for differentially expressed transcripts. The choice of an approach should depend upon particular features of the experiment and project requirements. We outline some general considerations to help decide between differential display-related techniques and subtractive hybridization. While discussing advantages and problems of differential display, special attention is given to several recently developed methods based on alternative principles of fingerprint production, which provide a possibility for complete systematic investigation of RNA samples.


Functional goal achievement in post-stroke spasticity patients: the BOTOX® Economic Spasticity Trial (BEST).
Evaluate changes in active and passive function with onabotulinumtoxinA + standard of care within goal-oriented rehabilitation programmes in adults with focal post-stroke spasticity. Prospective, 24-week double-blind study with an open-label extension. Subjects were randomized to onabotulinumtoxinA + standard of care or placebo + standard of care, at baseline and at 12 weeks, if judged appropriate, with follow-up to 52 weeks. The primary endpoint was the number of patients achieving their principal active functional goal at 24 weeks (or 10 weeks after an optional second injection). Secondary endpoints included achievement of a different active or a passive goal at this timepoint. The intent-to-treat population comprised 273 patients. The proportion of patients achieving their principal active functional goal and secondary active functional goal with onabotulinumtoxinA + standard of care was not statistically different from placebo + standard of care. Significantly more patients achieved their secondary passive goal with onabotulinumtoxinA + standard of care (60.0%) vs. placebo + standard of care (38.6%) (odds ratio, 2.46; 95% confidence interval, 1.18-5.14) as well as higher Goal Attainment Scaling levels for upper limb and ankle flexor subgroups. Addition of onabotulinumtoxinA to standard of care as part of goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function.