Dietary recommendations of magnesium for cardiovascular prevention and treatment. A position paper of the Israel Heart Society and the Israel Dietetic Association.
Modern life and the Western industrial diet has enhanced the reduction of magnesium in our food, which may contribute to a marginal or absolute magnesium deficiency. Magnesium deficiency is evident in, among others, the elderly population, those after myocardial infarction and/or chronic heart failure, and diabetics. In Israel, over 60% of the drinking water originates from desalinated seawater lacking magnesium, which may cause hypomagnesemia. Magnesium deficiency can easily be treated by magnesium supplementation if we are aware of the situation. This paper summarizes the magnesium chapter in a position paper published in April 2021 by the Israeli Cardiology Society together with the Israeli Dietetic Association. It summarizes evidence-based nutritional recommendations for prevention and treatment of cardiovascular disease, with emphasis on the level of evidence and practical recommendations according to the European Society of Cardiology definitions. The best recommendation is to increase consumption of magnesium-rich food, such as leafy green vegetables (mainly spinach), nuts, avocado, whole grains, legumes (e.g., beans, peas and soy beans), chocolate and certain seafood. However, for people who do not get sufficient magnesium from their diet completing the daily amount, as needed, with supplements of up to 600 mg/day should be considered. In addition, serum magnesium levels should be checked at least every six months in patients with heart failure, people taking diuretic therapy, and people taking proton-pump inhibitors. In addition, it may be beneficial to add magnesium following myocardial infarction in people with hypertension and in heart failure patients in order to reduce cardiovascular morbidity and mortality (class of recommendation IIa, level of evidence B).


Sex chromosomal and autosomal aneuploidy in the fragile X syndrome.
To date, the evidence to establish the association between aneuploidy and fragile sites, albeit thought-provoking, has been anecdotal and for the most part hypothetical. Studies with larger sample size and the use of RFLP analyses to establish parental origin of aneuploid states will undoubtedly resolve the issue. If an association between aneuploidy and fragile X and fragile site families is proved, this would have substantial impact on the counseling and management of these families. A confirmed association would direct investigators to determine common underlying biological factors leading to meiotic and mitotic nondisjunction.


Anatomy, immunology, digestive physiology and microbiota of the salmonid intestine: Knowns and unknowns under the impact of an expanding industrialized production.
Increased industrialized production of salmonids challenges aspects concerning available feed resources and animal welfare. The immune system plays a key component in this respect. Novel feed ingredients may trigger unwarranted immune responses again affecting the well-being of the fish. Here we review our current knowledge concerning salmon intestinal anatomy, immunity, digestive physiology and microbiota in the context of industrialized feeding regimes. We point out knowledge gaps and indicate promising novel technologies to improve salmonid intestinal health.


Effects of Nanodomains on Local and Long-Range Phase Transitions in Perovskite-Type Eu0.8Ca0.2TiO3-δ.
The determination of reversible phase transitions in the perovskite-type thermoelectric oxide Eu0.8Ca0.2TiO3-δ is fundamental, since structural changes largely affect the thermal and electrical transport properties. The phase transitions were characterized by heat capacity measurements, Rietveld refinements, and pair distribution function (PDF) analysis of the diffraction data to achieve information on the phase transition temperatures and order as well as structural changes on the local level and the long range. On the long-range scale, Eu0.8Ca0.2TiO3-δ showed a phase transition sequence during heating from cubic at 100 < T < 592 K to tetragonal and finally back to cubic at T > 846 K. The phase transition at T = 592 K (diffraction)/606 K (thermal analysis) was reversible with a very small thermal hysteresis of about 2 K. The local structure at 100 K was composed of a complex nanodomain arrangement of Amm2- and Pbnm-like local structures with different coherence lengths. Since in Eu0.8Ca0.2TiO3-δ the amount of Pbnm domains was too small to percolate, the competition of ferroelectrically distorted octahedra (Amm2 as in BaTiO3) and rigid, tilted octahedra (Pbnm as in CaTiO3) resulted in a cubic long-range structure at low temperatures.


Characteristics of patients undergoing medication-assisted -treatment for opioid use disorder and their interest in Tai Chi practice.
(1) To explore the characteristics of patients with opioid use disorder (OUD) maintained on either methadone or buprenorphine and (2) to determine the relative acceptability of integrating Tai Chi (TC) practice into an ongoing medication-assisted treatment for opioid use disorder (MOUD) program. Survey study. The University of Arkansas for Medical Sciences Center for Addiction Services and Treatment Program. 97 patients receiving MOUD treatment. Drug use history, treatment status, physical limitation, mental health, pain, and whether participants were interested in using TC to improve health outcomes. At least 30.9 percent of the sample reported moderate or higher level of limitation in performing rigorous physical activities, pain intensity, and pain interference. Between 37.1 and 61.5 percent of the sample reported various psychiatric symptoms. Methadone patients reported higher levels of physical limitations, especially in rigorous activities (p = .012), climbing several flights of stairs (p = .001), and walking more than a mile (p = .011), but similar levels of pain (ps = .664-.689) and psychiatric symptoms (ps = .262-.879) relative to buprenorphine patients. At least 40.2 percent of participants expressed moderate or higher level of interest in TC for improving health outcomes, with methadone patients more interested in participating to ease mental and sleep problems (p = .005) and improve physical fitness (p = .015) compared to buprenorphine patients. High prevalence of physical limitation, pain, and psychiatric comorbidities were found in OUD patients. Since patients were interested in TC to improve their health outcomes, this low-cost intervention, if proven effective, can be integrated into ongoing MOUD programs to improve health in this population.


Robust small molecule-aided cardiac reprogramming systems selective to cardiac fibroblasts.
Direct cardiac reprogramming to induce cardiomyocyte-like cells, e.g., by GMT (Gata4, Mef2c and Tbx5), is a promising route for regenerating damaged heart in vivo and disease modeling in vitro. Supplementation with additional factors and chemical agents can enhance efficiency but raises concerns regarding selectivity to cardiac fibroblasts and complicates delivery for in situ cardiac reprogramming. Here, we screened 2000 chemicals with known biological activities and found that a combination of 2C (SB431542 and Baricitinib) significantly enhances cardiac reprogramming by GMT. Without Gata4, MT (Mef2c and Tbx5) plus 2C could selectively reprogram cardiac fibroblasts with enhanced efficiency, kinetics, and cardiomyocyte function. Moreover, 2C significantly enhanced cardiac reprogramming in human cardiac fibroblasts. 2C synergistically enhances cardiac reprogramming by inhibiting Alk5, Tyk2 and downregulating Oas2, Oas3, Serpina3n and Tgfbi. 2C enables selective and robust cardiac reprogramming that can greatly facilitate disease modeling in vitro and advance clinical therapeutic heart regeneration in vivo.


Developmental Disruptions of the Dorsal Striatum in Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental condition characterized by social and communication deficits as well as patterns of restricted, repetitive behavior. Abnormal brain development has long been postulated to underlie ASD, but longitudinal studies aimed at understanding the developmental course of the disorder have been limited. More recently, abnormal development of the striatum in ASD has become an area of interest in research, partially due to overlap of striatal functions and deficit areas in ASD, as well as the critical role of the striatum in early development, when ASD is first detected. Focusing on the dorsal striatum and the associated symptom domain of restricted, repetitive behavior, we review the current literature on dorsal striatal abnormalities in ASD, including studies on functional connectivity, morphometry, and cellular and molecular substrates. We highlight that observed striatal abnormalities in ASD are often dynamic across development, displaying disrupted developmental trajectories. Important findings include an abnormal trajectory of increasing corticostriatal functional connectivity with age and increased striatal growth during childhood in ASD. We end by discussing striatal findings from animal models of ASD. In sum, the studies reviewed here demonstrate a key role for developmental disruptions of the dorsal striatum in the pathogenesis of ASD. Directing attention toward these findings will improve our understanding of ASD and of how associated deficits may be better addressed.


Effects of simulated high altitude (3800 m) on reproductive function in the pregnant rat.
Ovarian appearance, uterine contents (including numbers of fetuses, size and weight), and levels of gonadotropic hormones were studied in pregnant rats exposed to simulated altitude (3800 m). Comparisons were made at 11, 20 and 21 days of gestation between sea level controls rats bred at sea level and placed at reduced barometric pressure on confirmation of pregnancy (SHA). Although fewer fetuses were present in SHA rats on day 11 of gestation, litter size at days 20 and 21 was similar to controls. Body weight and length of SHA fetuses were significantly reduced by day 21 of gestation while placental weights remained similar to controls. The follicle-stimulating hormone (FSH) content in the pituitaries of SHA rats was significantly reduced at days 11 and 21 of pregnancy as compared with controls; luteinizing hormone (LH) content was lower at day 20 than at day 11 among SHA rats. Plasma gonadotropin levels were similar between SHA and control rats all all three stages of gestation. It is suggested that, despite lack of placental adaptation and altered endocrine functions, exposure of rats to hypoxic conditions only during gestation permits better maintenance of pregnancy than reported in rats with longer exposure to high altitude.


Interband recombination dynamics in resonantly excited single-walled carbon nanotubes.
Wavelength-dependent pump-probe spectroscopy of micelle-suspended single-walled carbon nanotubes reveals two-component dynamics. The slow component (5-20 ps), which has not been observed previously, is resonantly enhanced whenever the pump photon energy coincides with an absorption peak and we attribute it to interband carrier recombination, whereas we interpret the always-present fast component (0.3-1.2 ps) as intraband carrier relaxation in nonresonantly excited nanotubes. The slow component decreases drastically with decreasing pH (or increasing H+ doping), especially in large-diameter tubes. This can be explained as a consequence of the disappearance of absorption peaks at high doping due to the entrance of the Fermi energy into the valence band, i.e., a 1D manifestation of the Burstein-Moss effect.


Detachment of RAW264.7 macrophages from a culture dish using ultrasound excited by a Langevin transducer.
To study the relationship between macrophages and antigens, an efficient culture method for macrophages is important. During culture, macrophages adhering to the culture surface are difficult to harvest by general trypsinization. Thus, prolonged trypsinization or cell scraping has been used to detach macrophages. However, prolonged trypsinization has a negative effect on cell viability, and the detachment efficiency with cell scrapers depends highly on the skill of a technician. Therefore, we developed a macrophage-detaching method by combining trypsin-EDTA and ultrasonic vibration to detach cells from a ubiquitous culture vessel. We fabricated a device that propagated ultrasound to a φ-35-mm culture dish from underneath. To demonstrate our concept, RAW264.7 cells were used as model cells and exposed to several detaching conditions to evaluate the effects of our developed method. In addition to the proposed method, as traditional detaching methods, simple trypsinization with trypsin-EDTA and manual cell scraping were performed. Furthermore, to determine the optimal intensity of the ultrasound, input voltages into the ultrasound transducer of 200, 225, and 250 V were used. As a result, the number of live cells detached by the developed method with an input amplitude of 225 V was approximately 4.8 times more than that by simple trypsinization and approximately 4.3 times more than that by scraping. Furthermore, the proliferation and phagocytosis level of the cells were increased by the developed method at 225 V, while no significant difference was found in metabolism. Thus, the developed method improves culture efficiency and cell functions without causing metabolic disorders.


Grandparents Providing Care to Grandchildren: A Population-Based Study of Continuity and Change.
This study examines transitions in grandchild care and the characteristics of grandparents making these transitions, using longitudinal data from a nationally representative sample of 13,626 grandparents in the 1998-2008 Health and Retirement Study. More than 60% of grandparents provided grandchild care over the 10-year period; more than 70% of those did it for 2 years or more. Grandparents with fewer functional limitations and more economic resources were more likely to start or continue nonresidential care, whereas relatively disadvantaged grandparents were more likely to start and continue coresidential care. Grandparents who were African American, younger, married, living with fewer minor children of their own, or had more grandchildren were more likely to start care, particularly nonresidential care. African Americans and Hispanics were more likely than Whites to start and continue coresidential care. These findings demonstrate the heterogeneity of caregiving and point to the lack of resources among those who provide coresidential care.


Propagation of guided waves through weak penetrable scatterers.
The scattering of a scalar wave propagating in a waveguide containing weak penetrable scatterers is inspected in the Born approximation. The scatterers are of arbitrary shape and present a contrast both in density and in wavespeed (or bulk modulus), a situation that can be translated in the context of SH waves, water waves, or transverse electric/transverse magnetic polarized electromagnetic waves. For small size inclusions compared to the waveguide height, analytical expressions of the transmission and reflection coefficients are derived, and compared to results of direct numerical simulations. The cases of periodically and randomly distributed inclusions are considered in more detail, and compared with unbounded propagation through inclusions. Comparisons with previous results valid in the low frequency regime are proposed.


Distribution and histopathological changes induced by cysts of Taenia solium in the brain of pigs from Tanzania.
Neurocysticercosis (NCC) caused by Taenia solium cysts is a frequent but neglected parasitic disease of the central nervous system (CNS) worldwide. The aim of this study was to describe anatomical locations of cysts in the CNS and the corresponding inflammation. A total of 17 naturally infected pigs were used to evaluate the distribution of cysts and, of these, seven were used to evaluate the corresponding inflammation further, through histopathology. Clinical signs in the pigs included dullness, sluggishness, somnolence, apathy and loss of consciousness. Cysts were distributed in all cerebral lobes, i.e. 39.7% in the frontal lobe, 20.3% in the parietal lobe, 20.0% in the occipital lobe and 19.7% in the temporal lobe, and only 0.4% in the cerebellum. No cysts were found in the spinal cord. Cysts were localized as follows: 47.9% in the dorsal subarachnoid, 46.9% in the parenchyma, 4.4% in the subarachnoid base and 0.9% in the ventricles. The results of the histopathology revealed lesions in an early inflammatory stage, i.e. stage I, in all anatomical locations except for two, which showed more of an inflammatory reaction, stage III, in one pig. It was concluded that clinical signs in pigs were neither pathognomonic nor consistent. These signs, therefore, cannot be used as a reliable indicator of porcine NCC. Furthermore, T. solium cysts were found to be in abundance in all cerebral lobes, and only a few were found in the cerebellum. Regarding the inflammatory response, no significant differences were found in the location and total number of cysts. Thus, further studies are needed to explain the determinants of cyst distribution in the CNS and assess in detail clinical signs associated with porcine NCC.


Fast Thermoresponsive Poly(oligoethylene glycol methacrylate) (POEGMA)-Based Nanostructured Hydrogels for Reversible Tuning of Cell Interactions.
Reactive electrospinning is demonstrated as a viable method to create fast-responsive and degradable macroporous thermoresponsive hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA). Hydrazide- and aldehyde-functionalized POEGMA precursor polymers were coelectrospun to create hydrazone cross-linked nanostructured hydrogels in a single processing step that avoids the need for porogens, phase separation-driving additives, or scaffold postprocessing. The resulting nanostructured hydrogels can respond reversibly and repeatedly to changes in external temperature within seconds, in contrast to the minutes-to-hours response time observed with bulk hydrogels. Furthermore, nearly quantitative cell delamination can be achieved within 2 min of incubation at 4 °C, resulting in the recovery of as many or more (as well as more proliferatively active) cells from the substrate relative to the conventional trypsinization protocol. The combined macroporosity, nanoscale feature size, and interfacial switching potential of these nanostructured hydrogels thus offer promise for manipulating cell-hydrogel interactions as well as other applications in which rapid responses to external stimuli are desirable.


Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions.
Dendritic cells (DC) are potent antigen-presenting cells capable of inducing T and B responses and immune tolerance. We have characterized some aspects of energy metabolism accompanying the differentiation process of human monocytes into DC. Compared to precursor monocytes, DC exhibited a much larger number of mitochondria and consistently (i) a higher endogenous respiratory activity and (ii) a more than sixfold increase in ATP content and an even larger increase in the activity of the mitochondrial marker enzyme citrate synthase. The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability. Rotenone inhibited DC differentiation, as revealed by the observation that the expression of CD1a, which is a specific surface marker of DC differentiation, was strongly reduced. Cells cultured in the presence of rotenone displayed a lower content of growth factor-induced, mitochondrially generated, hydrogen peroxide. A similar drop in ROS was observed upon addition of catalase, which caused functional effects similar to those produced by rotenone treatment. These results suggest that ROS play a crucial role in DC differentiation and that mitochondria are an important source of ROS in this process.


[Circulation studies and transcranial Doppler sonography in orthostatic regulation disorders].
The effect of postural blood pressure changes on the blood flow velocity in the middle cerebral artery (MCA) was studied with transcranial Doppler sonography in 45 patients with intact circulatory reflexes and in 30 cases with postural hypotension. In an upright position on the tilt-table the patients with intact cardiovascular reflexes showed a small decrease of the MCA flow velocity of 3% (1.5 cm/sec), whereas there was found a marked reduction in the cases with postural hypotension. In the group with an asympathicotonic response (n = 14) there was an average decrease of 24% (13 cm/sec) and a 28% drop of mean arterial blood pressure. The lower percentage of reduction of the cerebral blood flow velocity can be explained as an effect of cerebral autoregulation. In the group with a sympathicotonic response (n = 16) a surplus reduction of the flow velocity of 17% (7 cm/sec) was seen, compared to a 7% decrease in blood pressure. This corresponds with the results of experimental animal studies which showed an impaired cerebral autoregulation during increased sympathico-adrenal discharge.


Detection of benz[j]aceanthrylene in urban air and evaluation of its genotoxic potential.
Benz[j]aceanthrylene (B[j]A) is a cyclopenta-fused polycyclic aromatic hydrocarbon with strong mutagenic and carcinogenic effects. We have identified B[j]A in air particulate matter (PM) in samples collected in Stockholm, Sweden and in Limeira, Brazil using LC-GC/MS analysis. Determined concentrations ranged between 1.57 and 12.7 and 19.6-30.2 pg/m(3) in Stockholm and Limeira, respectively, which was 11-30 times less than benzo[a]pyrene (B[a]P) concentrations. Activation of the DNA damage response was evaluated after exposure to B[j]A in HepG2 cells in comparison to B[a]P. We found that significantly lower concentrations of B[j]A were needed for an effect on cell viability compared to B[a]P, and equimolar exposure resulted in significant more DNA damage with B[j]A. Additionally, levels of γH2AX, pChk1, p53, pp53, and p21 proteins were higher in response to B[j]A than B[a]P. On the basis of dose response induction of pChk1 and γH2AX, B[j]A potency was 12.5- and 33.3-fold higher than B[a]P, respectively. Although B[j]A levels in air were low, including B[j]A in the estimation of excess lifetime cancer risk increased the risk up to 2-fold depending on which potency factor for B[j]A was applied. Together, our results show that B[j]A could be an important contributor to the cancer risk of air PM.


[Influence of imipramine on arousal from winter hibernation].
Imipramine (20 and 50 mg/kg intraperitoneally) is shown to delay the arousal of gophers from hibernation. This effect is similar to the action of serotonin (5 mg/kg) and 5-oxytryptophan (50 mg/kg). In the latter, however, the action on the thermogenesis is most pronounced and, because of this the warming up of the gophers is inhibited, while imipramine acts on the arousal. Tranylcypromine (20 mg/kg) failed to exert any substantial effect on the worming up and arousal of gophers from hibernation and attenuated the action of imipramine.


Synaptopathic mechanisms of neurodegeneration and dementia: Insights from Huntington's disease.
Dementia encapsulates a set of symptoms that include loss of mental abilities such as memory, problem solving or language, and reduces a person's ability to perform daily activities. Alzheimer's disease is the most common form of dementia, however dementia can also occur in other neurological disorders such as Huntington's disease (HD). Many studies have demonstrated that loss of neuronal cell function manifests pre-symptomatically and thus is a relevant therapeutic target to alleviate symptoms. Synaptopathy, the physiological dysfunction of synapses, is now being approached as the target for many neurological and psychiatric disorders, including HD. HD is an autosomal dominant and progressive degenerative disorder, with clinical manifestations that encompass movement, cognition, mood and behaviour. HD is one of the most common tandem repeat disorders and is caused by a trinucleotide (CAG) repeat expansion, encoding an extended polyglutamine tract in the huntingtin protein. Animal models as well as human studies have provided detailed, although not exhaustive, evidence of synaptic dysfunction in HD. In this review, we discuss the neuropathology of HD and how the changes in synaptic signalling in the diseased brain lead to its symptoms, which include dementia. Here, we review and discuss the mechanisms by which the 'molecular orchestras' and their 'synaptic symphonies' are disrupted in neurodegeneration and dementia, focusing on HD as a model disease. We also explore the therapeutic strategies currently in pre-clinical and clinical testing that are targeted towards improving synaptic function in HD.


Hepatotoxicity of paracetamol and related fatalities.
Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion. Repeated supratherapeutic misuse, non-intentional misuse, and intentional ingestion may all result in hepatic toxicity, the main cause of acute liver failure (ALF) in the United States and Europe. Since paracetamol is responsible for nearly half of the cases in the US of acute liver failure and remains the leading cause of liver transplantation, continued awareness promotion, education and research should be constantly undertaken. We herein review the literature on paracetamol toxicity with particular attention to aspects of liver damage and related fatalities.


Analysis of the factors affecting school attendance in pediatric fractures.
This study aimed to examine the average duration of school absence according to the type of fracture and the factors affecting the duration of absence in children who had difficulty going to school after an acute orthopedic injury. Patients between the ages of 6 and 17 who applied to the emergency department of our hospital and were treated for orthopedic trauma during a teaching period between September 2022 and December 2022 were examined. This study was designed prospectively. All school-aged patients with upper or lower extremity fractures requiring hospitalization or outpatient treatment were included in this study. Information about school absences and school starting dates were recorded at the outpatient clinical presentations of these patients. A total of 126 patients were included in this study. The mean age of the patients was 11.7 (range=6-17) years. The gender ratio was determined as F/M=20/106. The average time absent from school was 14.7 (range=2-61) days. Distal radius fractures were the most common upper extremity fractures; the mean time away from school was 7.9 days. In lower extremity fractures, lateral malleolar fracture was the most common complaint, and the mean duration of absence was calculated as 21.8 days. The periods of absence were mainly determined by the family or the child. One of the critical findings in this study was that rest periods were primarily determined by the parents and/or the child and not by the physician. The need to use crutches and/or transportation difficulties were other reasons for the absence. For these reasons, teachers and school management should be sensitive to the adverse effects of absenteeism on the child's success and provide facilitating support and home education opportunities when necessary. Level II, Prognostic study.


Major and minor depression in Alzheimer's disease: prevalence and impact.
One hundred nine outpatients with Alzheimer's disease (AD) were neuropsychiatrically evaluated and rated on standardized measures of depression, activities of daily living (ADL), nonmood behavioral disturbance, and burdensome events such as serious wandering, falls, and accidents. Distribution of depression scores revealed three patient groups: very few depressive symptoms (51%), minor depression (27%), and major depression (22%). Major depression was associated with substantially greater impairment in ADL, worse nonmood behavioral disturbance (such as aggression), and more frequent serious wandering, even after adjusting for severity of dementia or comorbid health problems. Minor depression was also associated with nonmood behavioral disturbance and wandering. The authors conclude that both major and minor depression are common in AD and produce considerable mood and nonmood morbidity affecting both patients and caregivers. Efforts are warranted to identify and treat depression in AD.


Clinical impact of patients with ruptured esophageal varices with death outcome.
High hemostasis rates for ruptured esophageal varices have been acquired, but many patients die of liver failure afterwards. The aim of the current study is to find clinical information about the patients with ruptured esophageal varices who died during an early period after acquiring a hemostasis. Forty-five patients with ruptured esophageal varices, including 17 who died during two months after acquiring a hemostasis by an initial endoscopic therapy, were investigated in the current study. The relationship between the clinical data and the prognosis of the patients were examined. The proportion of cases with Child-Pugh C in patients who died after therapy significantly higher than that in survivors (P < 0.01). The level of hemoglobin in patients who died was significantly lower than that in the survivors (P < 0.01). Moreover the proportion of an elevation of serum C-reactive protein in patients who died was significantly higher than that of the survivors (P < 0.05). Our investigation suggested that the elevation of serum C-reactive protein level and a devastated liver function influenced by hemorrhage may be indicators of unfavorable outcomes of the patients with ruptured esophageal varices.


Robust laser frequency stabilization by serrodyne modulation.
We report the relative frequency stabilization of a distributed feedback erbium-doped fiber laser on an optical cavity by serrodyne frequency shifting. A correction bandwidth of 2.3 MHz and a dynamic range of 220 MHz are achieved, which leads to a strong robustness against large disturbances up to high frequencies. We demonstrate that serrodyne frequency shifting reaches a higher correction bandwidth and lower relative frequency noise level compared to a standard acousto-optical modulator based scheme. Our results allow us to consider promising applications in the absolute frequency stabilization of lasers on optical cavities.


Proof of the patent subcutaneous fibrous tract in children with V-P shunt malfunction.
A connective tissue sheath that forms around the peritoneal catheter of silicone ventriculo-peritoneal (V-P) shunt tubing is quite often observed in children with V-P shunts. However, proof of the passage of cerebrospinal fluid (CSF) through these sheaths has been reported in only one published study to date. We present four cases associated with chronic malfunction of the V-P shunt peritoneal catheter. In these cases, CSF passage through the subcutaneous fibrous tract, which had a pericatheter connective tissue sheath, was demonstrated around the V-P shunt peritoneal catheter. In the first case the patient suffered intermittent headache attacks over a long period of time; abdominal migration of the peritoneal catheter was detected. The second patient, who had been asymptomatic in the follow-up period with an outgrown peritoneal catheter, was admitted with acute hydrocephalus symptoms. A peritoneal catheter disconnection was detected in another patient, who had had multiple shunt revisions previously. In the last case, an obstruction of the peritoneal catheter was detected. The existence of the subcutaneous fibrous tract and its function were demonstrated by radio-opaque shuntogram in two cases and radionuclide shuntogram in the other two cases. In all four cases V-P shunt revision was performed. Within this study, the possible passage of CSF through a fibrous tract in cases of migration, outgrowth, disconnection or obstruction of the peritoneal shunt catheter was demonstrated. In conclusion, patients with shunt malfunction with a well-grown pericatheter fibrous sheath who are either asymptomatic or minimally symptomatic and show no evidence of active ventricular dilatation on their cranial CT scan should not be regarded as having arrested hydrocephalus until radio-opaque or radionuclide shuntogram studies have been done.


"The Lower Threshold" phenomenon in tumor cells toward endogenous digitalis-like compounds: Responsible for tumorigenesis?
Since their first discovery as potential anti-cancer drugs decades ago, there is increasing evidence that digitalis-like compounds (DLC) have anti-tumor effects. Less is known about endogenous DLC (EDLC) metabolism and regulation. As stress hormones synthesized in and secreted from the adrenal gland, they likely take part in the hypothalamo-pituitary-adrenal (HPA) axis. In a previous study, we revealed reduced EDLC concentrations in plasma and organs from immune-compromised animals and proposed that a similar situation of a deregulated HPA axis with "adrenal EDLF exhaustion" may contribute to tumorigenesis in chronic stress situations. Here, we put forward the hypothesis that a lowered EDLC response threshold of tumor cells as compared with normal cells increases the risk of tumorigenesis, especially in those individuals with reduced EDLC plasma concentrations after chronic stress exposure. We will evaluate this hypothesis by (a) summarizing the effects of different DLC concentrations on tumor as compared with normal cells and (b) reviewing some essential differences in the Na/K-ATPase of tumor as compared with normal cells (isoform pattern, pump activity, mutations of other signalosome receptors). We will conclude that (1) tumor cells, indeed, seem to have their individual "physiologic" EDLC response range that already starts at pmolar levels and (2) that individuals with markedly reduced (pmolar) EDLC plasma levels are predisposed to cancer because these EDLC concentrations will predominantly stimulate the proliferation of tumor cells. Finally, we will summarize preliminary results from our department supporting this hypothesis.


Early experience with a modified preloaded system for fenestrated endovascular aortic repair.
Preloaded endovascular delivery systems expand the anatomic eligibility for complex aortic repair by requiring only one iliac access vessel and providing a stable platform for guiding sheaths into challenging target vessels. This article reports the lessons learned and early clinical outcomes using a modified preloaded delivery system for fenestrated endovascular aneurysm repair (FEVAR) in three aortic centers in Europe. From October 2015 to March 2016, consecutive patients presenting with extensive aortic aneurysm treated with a modified preloaded FEVAR were prospectively enrolled from three high volume European aortic centers. The new design is a modification of previous designs of preloaded fenestrated stent grafts and of the p-branch device platform. The technical details of implantation are described and perioperative outcomes, including the learning curve, are collected and reported. All patients (30 patients; 80% men; 70.2 years old) presented for nonurgent repair of either a type Ia endoleak (3/30; 10%), a type I-II-III thoracoabdominal (8/30; 27%), or a type IV thoracoabdominal or pararenal (19/30; 63.%) aneurysm repair of a mean size of 64 ± 13 mm using a custom made device. Primary technical success was achieved in 28 of 30 patients (93%) and assisted primary technical success in 29 of 30 patients (97%). The two technical failures included open conversion to repair a ruptured iliac artery and restenting of a dissected superior mesenteric artery which was recognized hours after the index procedure had finished. The mean procedure time was 277 ± 153 minutes, fluoroscopy time 79 ± 36 minutes, dose area product 112 ± 90 Gy cm2, and contrast volume 87 ± 46 mL. All renal fenestrations were successfully stented without type III endoleak on completion angiogram; the preloaded guiding sheaths were used for 53 of 58 renal arteries (91%). Challenges related to learning to the use of the modified preloaded system were experienced early and had no clinical consequences. Major complications occurred in seven cases (23%), including two perioperative deaths because of stroke and sepsis following primary conversion attributable to iliac rupture. There were no target vessel occlusions or type I/III endoleaks found on postoperative imaging. Based on early experience, the modified preloaded system can be safely and effectively used during FEVAR, with good technical result and a short period of learning. This device expands treatment to patients with compromised iliac access, thus, additional patients and more follow-up will be required to determine unique risks of operating in this patient population.


[Action of vitamin E on the normal myocardial energy balance and in ischemia and reoxygenation].
The energy mechanisms of formation of anti-ischemic myocardial resistance have been studied by means of vitamin E, administered to rats 24 hours before modelling ischemia in a dose of 200 mg/kg, in which the antioxidant activity of the preparation is pronounced. At the stage of ischemia, myocardial energy was studied by the differential calorimetry method, in the pre- and postischemic periods on a functioning heart in a stand according to Neely. It is shown, that vitamin E in ischemic and postischemic periods enhances the power and efficiency of myocardial energy consumptions: decreases irrational energy consumptions in the initial period of ischemia (the first 15 minutes) and supports a higher level of energy production further on, increasing thus the admissible periods of myocardial ischemia from 20-25 to 30-35 minutes, maintains in the postischemic period a higher level of total useful energy consumptions and coefficients of the oxygen utilization efficiency as compared with the experiments without preliminary administration of vitamin E. It is shown, that the anti-ischemic defence of the myocardium by vitamin E is formed already in the preischemic period and conditioned by redistribution of energy consumptions and growth of the share of energy consumptions aimed at the maintenance of the initial structural-functional homeostasis of myocardial cells.


Trauma and posttraumatic stress disorder in an urban Xhosa primary care population: prevalence, comorbidity, and service use patterns.
Despite increased awareness of the prevalence and morbidity of psychiatric illnesses, relatively few studies have been undertaken in primary care settings in the African context. The authors determined the prevalence of trauma exposure and posttraumatic stress disorder (PTSD) in a South African township primary health care clinic and assessed associated demographic factors, comorbidity, service use, service satisfaction, and quality of life. Subjects were directly interviewed using translated, standardized instruments to assess variables described. Retrospective chart analysis assessed clinician case identification and psychotropic drug-prescribing habits. Of the 201 participants, 94% reported exposure to traumatic events (mean, 3.8). Trauma was associated with single status (p =.01), and PTSD was associated with poverty and single status (p =.04). Both sexes were equally likely to develop PTSD. PTSD (current; 19.9%), depression (37%), and somatization disorder (18.4%) were the most common diagnoses. Comorbidity with PTSD was high and included depression (75%, p <.01), somatization (35%, p <.01), and panic disorder (25%, p <.01). Levels of functional impairment were higher for subjects with PTSD, depression, and somatization than for those without (p <.05). PTSD comorbid with depression compounded impairment (p =.04). Levels of trauma, PTSD, and depression did not increase service use or dissatisfaction with services. Clinicians did not identify trauma (0%) or psychopathology (0%), and psychotropic medication was prescribed for only 1% of participants. In this population, trauma and PTSD were highly prevalent and associated with significant unidentified morbidity and comorbidity. Patients remain untreated for years in the current system of primary care consultations.


Evaluation of Supranormal Spirometry Values With an Obstructive Ratio for Airway Hyperreactivity.
Published guidelines on spirometry interpretation suggest an elevated FVC and FEV1 > 100% of predicted with an obstructive ratio may represent a physiological variant. Further evidence is needed on whether this finding indicates symptomatic airways obstruction and what additional evaluation should be done. Participants were prospectively enrolled to undergo additional testing for a technically adequate spirometry study with an FEV1 > 90% of predicted, and FEV1/FVC below the lower limit of normal, based on 95th percentile confidence intervals. Further testing consisted of full pulmonary function testing, impulse oscillometry (IOS), post-bronchodilator testing, fractional exhaled nitric oxide (FeNO), and methacholine challenge testing (MCT). A total of 49 patients meeting entry criteria enrolled and completed testing. Thirty-three were considered symptomatic based on clinical indications for initial testing and 16 were considered asymptomatic. Baseline pulmonary function test values were not different between groups while IOS R5 values (% predicted) were higher in the symptomatic group (126.5 ± 0.37 vs 107.1 ± 0.31). Bronchodilator responsiveness on PFT or IOS was infrequent in both groups. There was a 29% positivity rate for MCT in the symptomatic group compared to one borderline study in asymptomatic participants. FeNO was similar for symptomatic, 26.17 ± 31.3 ppb, compared to asymptomatic, 22.8 ± 13.5 ppb (p = 0.93). The dysanapsis ratio was higher in the symptomatic (0.15 ± 0.03) compared to the asymptomatic (0.13 ± 0.02) (p < 0.05). Normal FEV1 > 90% of predicted and obstructive indices may not represent a normal physiological variant in all patients. In symptomatic patients, a positive MCT and elevated baseline IOS values were more common than in asymptomatic patients with similar PFT characteristics. These findings suggest that clinicians should still evaluate for airway hyperresponsiveness in patients with exertional dyspnea with airway obstruction and FEV1 > 90% of predicted and consider alternative diagnoses to include a normal physiologic variant if non-reactive.


The site-specific ribosomal DNA insertion element R1Bm belongs to a class of non-long-terminal-repeat retrotransposons.
Two types of insertion elements, R1 and R2 (previously called type I and type II), are known to interrupt the 28S ribosomal genes of several insect species. In the silkmoth, Bombyx mori, each element occupies approximately 10% of the estimated 240 ribosomal DNA units, while at most only a few copies are located outside the ribosomal DNA units. We present here the complete nucleotide sequence of an R1 insertion from B. mori (R1Bm). This 5.1-kilobase element contains two overlapping open reading frames (ORFs) which together occupy 88% of its length. ORF1 is 461 amino acids in length and exhibits characteristics of retroviral gag genes. ORF2 is 1,051 amino acids in length and contains homology to reverse transcriptase-like enzymes. The analysis of 3' and 5' ends of independent isolates from the ribosomal locus supports the suggestion that R1 is still functioning as a transposable element. The precise location of the element within the genome implies that its transposition must occur with remarkable insertion sequence specificity. Comparison of the deduced amino acid sequences from six retrotransposons, R1 and R2 of B. mori, I factor and F element of Drosophila melanogaster, L1 of Mus domesticus, and Ingi of Trypanosoma brucei, reveals a relatively high level of sequence homology in the reverse transcriptase region. Like R1, these elements lack long terminal repeats. We have therefore named this class of related elements the non-long-terminal-repeat (non-LTR) retrotransposons.


A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative.
While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette-Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.


Claims-Based Reporting of Post-Operative Visits for Procedures with 10- or 90-Day Global Periods: Updated Results Using Calendar Year 2019 Data.
Medicare payments for most surgical procedures cover both procedures and post-operative visits occurring within a global period of either 10 or 90 days following procedures. There have been concerns that fewer post-operative visits are provided than the number of post-operative visits considered when the procedure was valued. To help inform accurate valuation of procedures with global periods, the Centers for Medicare & Medicaid Services (CMS) required select practitioners to report on post-operative visits after select procedures with 10- or 90-day global periods. The authors of this article summarize patterns of post-operative visits for procedures furnished during calendar year 2019, building on prior research that analyzed data for procedures furnished from July 1, 2017, through June 30, 2018, and for the entire 2018 calendar year. During calendar year 2019, 96.5 percent of procedures with 10-day global periods did not have an associated post-operative visit. Approximately two-thirds of procedures with 90-day global periods had an associated post-operative visit; however, the ratio of observed to expected post-operative visits provided for 90-day global period procedures was only 0.38. Underreporting of post-operative visits might be driving these low rates. However, in sensitivity analyses limited to practitioners who were actively reporting their post-operative visits, post-operative patterns were largely similar to the main analysis. Collectively, these findings suggest that many expected post-operative visits are not delivered and that underreporting is unlikely to fully explain the low ratio of expected post-operative visits provided.


Modification of radiation effects in single-cell systems by membrane-binding agents.
Chlorpromazine sensitized E. COLI B/r, thymocytes and Yoshida ascites-tumour cells to 60Co gamma-rays, preferentially, under hypoxic conditions, Residual sensitization was observed in E. coli B/r. The radiosensitization by chlorpromazine was found to be due to the reaction of radiolytically-induced hydroxyl radicals with the sensitizer. When both procaine HCI and chlorpromazine were present during anoxic irradiation of E. coli B/r, there was no additive effect. But the addition of procaine HCL after irradiation to cell sensitized by chlorpromazine had an effect that was significantly greater than that produced even by oxygen. A similar effect was observed when lignocaine or tetracaine was used in place of procaine. The possible mechanisms involved in radiosensitization by chlorpromazine and in the post-irradiation effect of local anaesthetics in cells sensitized to 60Co gamma-rays by chlorpromazine are discussed.


Six Transmembrane Epithelial Antigen 1 as a Prognostic Biomarker in Carcinomas: A Meta-Analysis.
Six transmembrane epithelial antigen 1 (STEAP1) is aberrantly expressed in cancers and could therefore be a potential biomarker. This study examined the connection between STEAP1 expression and clinical features/prognosis in cancer patients. Several databases were comprehensively searched for related published studies. The combination of hazard ratios (HRs), odd ratios (ORs), and 95% confidence intervals (95% CIs) was used to assess the role of STEAP1. The Cancer Genome Atlas (TCGA) dataset was used to estimate the prognostic value of STEAP1 in multiple cancer types, and several biological behaviors related to STEAP1 were evaluated by CancerSEA. Searches of electronic databases revealed 7 relevant trials with 765 patients. A significant connection was found between high STEAP1 expression and worse overall survival amongst cancer patients (HR = 1.87, 95% CI: 1.49-2.34, p < 0.001). In addition, a strong correlation was found between high STEAP1 expression and the occurrence of lymph node metastases (OR = 3.19, 95% CI: 1.26-8.09, p < 0.001). Analysis of TCGA datasets verified that a higher level of STEAP1 expression is linked with reduced survival in many kinds of cancer. At the single cell level, STEAP1 expression was correlated with some tumor biological behaviors, such as angiogenesis, quiescence, and stemness. STEAP1 could regulate various biological functions in tumors and predict prognosis as a novel biomarker in a number of cancer types.


A two-step quality-improvement intervention to address Pap smear quality at public health facilities in South Africa.
The endocervical component of a Pap smear is an important indicator of sample quality - or 'adequacy'. However, only 6 of 52 districts in South Africa (SA) meet the Department of Health (DoH) performance benchmark: a 70% adequacy rate. We implemented a quality-improvement (QI) intervention to address suboptimal Pap smear quality in Tshwane District, Gauteng Province, SA. To determine whether training with the wooden Ayre spatula (step 1) or introduction of the cytobroom (step 2) resulted in greater improvements in Pap smear adequacy rates. Two Tshwane District health facilities participated in our QI project between May 2016 and February 2017. In step 1, staff received training on the Ayre spatula. In step 2, the spatula was replaced with the cytobroom. Pap smear volumes, adequacy rates and results are reported for the pre-intervention period and after each QI step. We compared adequacy rates using Fisher's exact test, with a significance level of p=0.05. In the pre-intervention period, 304 of 965 Pap smears were deemed adequate (32%; 95% confidence interval (CI) 29 - 35%). After step 1, the proportion increased to 109 of 191 (57%; 95% CI 50 - 64%; p<0.01). Similarly, after step 2, the proportion increased to 155 of 192 (81%; 95% CI 74 - 86%; p<0.01). The proportion of abnormal smears increased from 13% before the QI intervention to 17% after step 1 and 22% after step 2. Although training in Pap smear collection using the Ayre spatula resulted in modest improvements in quality, facilities only achieved the DoH benchmark of a 70% adequacy rate after the introduction of the cytobroom.


[Spectrographic study of voice disorders: subharmonics].
The presence of subharmonics in abnormal adult voices (polyps, polypoid degeneration, plicae ventricularis) was investigated. Subharmonics are low-frequency modulations located between two consecutive harmonics in the spectrum. Spectrum analysis was performed on 115 abnormal voices, of which 36 (31%) had subharmonics. Thirteen of the 36 voices with subharmonics had normal jitter and shimmer, so the rough voice was characterized acoustically not only by jitter and shimmer but by the presence of subharmonics in the spectrum. Subharmonics may correspond to a qualitative change in the behavior of the vibratory system.


Clinical significance of specific IgE determination on nasal secretion.
The clinical use of RAST on the nasal secretions was investigated in seventeen atopic patients, with asthma or rhinitis, who had shown at a first diagnostic screening, some difficulties in the identification of the responsible allergen(s). The results of the skin tests, of the RAST on the serum and on the nasal secretions and of the specific provocation test (bronchial or nasal) were compared. In some cases the basophil degranulation test was performed. The results of the RAST on the nasal secretions were in perfect agreement with the provocation test. The skin tests and the RAST on the serum showed many discrepancies, particularly for Dermatophagoides, epidermal derivatives of cat and dog and moulds, and less frequently for Graminaceae and other pollens. It is concluded that RAST analysis on nasal secretions is useful in clinical diagnosis of allergy especially for Dermatophagoides, epidermal derivatives and moulds. Most false positive results were observed with the RAST on serum; in fifteen cases it was positive, while all the other tests, basophil degranulation test included, were negative. The data suggest that IgE may have a low affinity for basophil receptors.


Enhanced supercritical fluid carbon dioxide extraction of pesticides from foods using pelletized diatomaceous earth.
Supercritical fluid carbon dioxide (SC-CO2), when used with an extraction enhancer, comprises a supercritical fluid extraction (SFE) system for extraction of pesticides and matrix components from fatty and nonfatty foods. After being mixed with the enhancer, samples ranging from 95% water to pure lipophilic oils can be extracted efficiently with SC-CO2. This extraction technique yields analyte recoveries in excess of 85% for over 30 types of pesticides at incurred levels ranging from 0.005 to 2 ppm in such diverse matrixes as carrots, lettuce, peanut butter, hamburger, and fortified butter fat and fortified potatoes. SC-CO2 provides a solvent medium that is nontoxic, nonflammable, and inexpensive while also eliminating the use and disposal of potentially carcinogenic organic solvents.


[The influence of smoking on fertility, pregnancy and lactation]
OBJECTIVE: To decribe the influence of smoking on different phases of the reproductive process, fecundation, pregnancy and lactation, drawing special attention to the mechanisms of action of the main toxic components found in cigarettes. To suggest prophylactic measures for environmental control and how to reduce childreńs exposure to tobacco smoke. METHODS: Nonsystematic literature review using MEDLINE database. RESULTS: Smoking has a negative effect on different phases of the reproduction process, by direct action of main toxic components, nicotine and carbon monoxide. Smoking reduces fertility, compromises the length of gestation and infant birthweight. Smoking mothers also have reduced breast milk production and shorter lactation, which affects infant weight gain through unclear mechanisms in which prolactin may probably be involved. CONCLUSIONS: Smoking compromises reproductive function quality in different phases, acting mainly on intrauterine and extrauterine development of infants. Since during pregnancy and lactation women are in closer contact with health professionals, antismoking campaigns should be especially addressed to this period.


Analysis of flow field characteristics of sand removal hydrocyclone applicable to solid fluidization exploitation of natural gas hydrate.
With the development of economy and society, the consumption of fossil energy is gradually increasing. In order to solve the current energy dilemma, Natural gas hydrate (NGH) is considered as an ideal alternative energy. At the same time, solid fluidization exploitation is an ideal method. However, in the process of that, sand and hydrate ore bodies enter the closed pipeline together, which will block the pipeline and increase the difficulty of exploitation. Therefore, the pre-separation of sand by hydrocyclone plays an important role in solid fluidization exploitation. In this study, the numerical simulation method was used to study the internal flow field characteristics of the hydrocyclone, and the effects of different flow rate, different flow ratio, different sand content and different particle diameter on the phase distribution were investigated. The results show that: at the same axial position, the increase of flow rate and sand content makes the sand phase more distributed at the edge of the flow field. Under the same working conditions, the sand gradually migrates to the center of the flow field with the increase of the axial distance. By calculation, it is obtained that under the optimum working condition of the flow rate is 4.83m3/h, the flow ratio is 20%, the sand content is 20%, and sand diameter is 80μm, the maximum Es is 22.1% and the minimum is 86.1%. Finally, a comprehensive analysis of the hydrocyclone in this study shows that this hydrocyclone is only applicable to rough pre-separation of sand in the process of solid fluidization exploitation. Through the study of the internal flow field characteristics and phase distribution law of the hydrocyclone, this study provides a reference for the practical engineering application of sand phase pre-separation in the solid fluidization exploitation of NGH.


Cytomegalovirus-related necrotising vasculitis mimicking Henoch-Schönlein syndrome.
Viral vasculitides have been previously reported in the literature, the role of infections in their pathogenesis ranging from direct cause to trigger event. Here we report the case of a 3-year-old immunocompetent girl who developed a systemic vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch-Schönlein purpura. High dosage steroid treatment was started, with good response. The anatomopathological examination of the resected gastrointestinal tract showed features of necrotising vasculitis and cytomegalovirus (CMV)-related inclusion bodies in the endothelial cells, with direct correlation to vascular damage. The causative role of viral infection was revealed by the presence of CMV DNA in patient's blood and positive IgG titer against the virus. Steroid therapy was then tapered: the patient achieved clinical remission, which still persists after a six-months follow-up. Our report suggests that CMV vasculitis is probably more frequent than previously thought, even in immunocompetent patients, with a protean clinical presentation, mimicking other types of vasculitides.


[Effect of inhibitory-inhibitory connections and the form of postsynaptic potentials on the formation of rhythmic processes in the cerebral cortex: analysis of the approximate equation of the electroencephalogram].
The integral equation, describing the electroencephalogram and taking into account the steepness of PSP fronts, delays of action potential spread, and neural Inhibito-inhibitory connections, is derived and analysed. The damping decrements and frequencies of the equation solutions in the continuum of parameters, associated with total numbers excitatory and inhibitory neurons in the cerebral cortex, density of synapses, and average level of excitation of cortical neurons are considered. The steepness of PSP fronts does not qualitatively change the solution's structure with the influences of EPSP and IPSP fronts being opposite. The inhibito-inhibitory connections expand the damped solutions regions. The delays of action potential spread between excitatory neurons enlarge the damped solutions region, and the delays in ones between inhibitory and excitatory neurons decrease it, especially for higher frequencies.


Neonatal hypertrichosis in an infant of a diabetic mother with congenital hypothyroidism.
Hypertrichosis in a newborn girl infant of a diabetic mother with congenital hypothyroidism is reported. Both neonatal hyperinsulism and increased testosterone levels were documented. The hypertrichosis resolved after 3 months' of thyroxine replacement treatment. The possible causal association between hypothyroidism, and hypertrichosis has not been previously reported in neonatal period. Thyroid function should be evaluated in all newborn babies with hypertrichosis or abnormal distribution of body hair.


Clinical significance of serum epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients with epithelial ovarian cancer.
Cellular adhesion molecules might be good markers in some types of malignant tumors, useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) in epithelial ovarian cancer (EOC) patients. Fifty patients were enrolled into the study. Serum EPCAM and VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of the patients was 56.5 years, range 22 to 83 years. Majority of the patients had advanced disease (stages III-IV) (90%). The baseline serum EPCAM levels of the EOC patients were significantly higher than in those in the control group (p = 0.03). However, there was no significant difference in the serum VCAM-1 level between EOC patients and controls (p = 0.24). Metastatic patients had higher serum VCAM-1 levels compared with the non-metastatic patients (p = 0.03). Moreover, no other clinical variables including response to chemotherapy were found to be correlated with both serum assays (p > 0.05). No correlation was found between serum EPCAM and VCAM-1 levels in EOC patients (r(s) = 0.105, p = 0.362). Neither serum EPCAM level nor serum VCAM-1 level had significant adverse effect on survival. In conclusion, the higher baseline serum levels of VCAM-1 were associated with metastatic disease, and serum EPCAM level was found to be a diagnostic marker in EOC patients. However, both serum assays had no prognostic roles on outcome.


Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters.
Yondelis is a potent DNA-binding anticancer drug isolated from the tunicate Ecteinascidia turbinata currently undergoing phase III clinical trials. We and others have shown selective inhibition to the transcriptional induction of several genes. We tested the hypothesis that Yondelis specifically targets cell-cycle genes. Our analysis on endogenous and transfected reporter systems revealed complex patterns of transcriptional inhibition and, surprisingly, activation. Other inducible systems-the metallothionein and the CYP3A4 promoters-were little affected. We assayed whether interference of DNA binding of the common nuclear factor Y (NF-Y) activator was responsible for the observed inhibition: in vivo chromatin immunoprecipitation analysis in NIH3T3 and HCT116 cells indicates that NF-Y binding is little affected by Yondelis addition. Finally, histone acetylation was modestly affected only on Cdc2 and cyclin B2 but not on other repressed promoters. These data prove that Yondelis is not a general inhibitor of inducible genes, and its selective effects are exerted downstream from transcription factors binding and histone acetyl transferases recruitment.


Electromyographic and kinematic analysis of the shoulder during four activities of daily living in men with C6 tetraplegia.
The pattern of motor paralysis that commonly follows C6 tetraplegia creates an increased demand on upper limb function. The present investigation documented shoulder motion and muscular activity during planar motions and four activities of daily living (ADLs) in 15 men with spinal cord injuries (SCI) resulting in C6 tetraplegia. Three-dimensional (3-D) shoulder motion was recorded using a VICON motion system, and intramuscular electrodes recorded electromyographic (EMG) activity of 12 shoulder muscles. Active flexion and abduction required greater EMG than control subjects lifting a 2-kg weight. Relative EMG was similar for most muscles during hair combing, drinking, and reaching forward, although increased humeral elevation commonly resulted in a greater relative muscular effort. Hair combing had the most humeral elevation (90 degrees) with moderate to high levels of activation (32% to 63% maximum) recorded in the anterior deltoid, supraspinatus, infraspinatus, and scapular muscles. During reaching for the perineum, posterior deltoid and subscapularis activity dominated.


Bone marrow transplantation reproduces the tristetraprolin-deficiency syndrome in recombination activating gene-2 (-/-) mice. Evidence that monocyte/macrophage progenitors may be responsible for TNFalpha overproduction.
Tristetraprolin-deficient [TTP (-/-)] mice exhibit a complex syndrome of myeloid hyperplasia, cachexia, dermatitis, autoimmunity, and erosive arthritis. Virtually the entire syndrome can be prevented by the repeated injection of anti-TNFalpha antibodies (Taylor, G.A., E. Carballo, D.M. Lee, W.S. Lai, M.J. Thompson, D.D. Patel, D.I. Schenkman, G.S. Gilkeson, H.E. Broxmeyer, B.F. Haynes, and P.J. Blackshear. 1996. Immunity. 4:445-454). In the present study, we transplanted bone marrow from TTP (-/-) and (+/+) mice into recombination activating gene-2 (-/-) mice. After a lag period of several months, marrow transplantation from the (-/-) but not the (+/+) mice resulted in the full syndrome associated with TTP deficiency, suggesting that hematopoietic progenitors are responsible for the development of the syndrome. Western blot analysis of supernatants from cultured TTP-deficient macrophages derived from the peritoneal cavity or bone marrow of adult TTP (-/-) mice, or from fetal liver, demonstrated an increased accumulation of TNFalpha after stimulation with LPS compared to control cells, and also increased accumulation of TNFalpha mRNA. This difference was not observed with cultured fibroblasts or T and B lymphocytes. These data suggest that macrophages are among the cells responsible for the effective excess of TNFalpha that leads to the pathology reported in TTP (-/-) animals, and that macrophage progenitors may be involved in the transplantability of this syndrome.


Hepatocellular carcinoma presenting with intractable diarrhea. A radiologic-pathologic correlation.
A 44-year-old woman with hepatocellular carcinoma presented with intractable watery diarrhea and her condition was evaluated angiographically. Surgical ablation of the tumor resulted in complete resolution of the diarrhea. The tumor cells of the hepatocellular carcinoma were found to contain vasoactive intestinal polypeptide, gastrin, and prostaglandinlike immunoactivity. To our knowledge, this is the first report of such an association.


Factors affecting patients' and potential patients' choices among anaesthetics for periodontal recall visits.
Dentinal hypersensitivity and recurrent disease may necessitate the use of anaesthetic during periodontal recall visits. However, an aversion to injections may affect patient compliance. The objectives of this study were to determine choices patients and 'potential' patients make when provided with information on the risks and benefits of alternative anaesthetic choices for root planing during periodontal recalls and to examine which factors influence these choices. Using an interactive computer tool, scenarios described the risks and benefits of root planing during periodontal maintenance and the anaesthetic alternatives (no anaesthetic, an experimental thermosetting gel anaesthetic and traditional local infiltration anaesthesia). Compliant patients for whom anaesthesia was recommended during recall cleanings were recruited from private periodontal practices (n=97). General population subjects (potential patients) were recruited by random digit dialing (n=196) As dental insurance was one of the inclusion criteria, the sample was representative of a working population. Most subjects reported tooth sensitivity (recall 84.5%, general 59.9%). The majority of patients wanted some form of anaesthetic, either gel (recall 82.5%, general 81.0%) or local infiltration (recall 10.3%, general 16.4%). Fifty-five percent of subjects reported moderate or severe pain from their previous dental injection(s). Asked if they were to have a dental needle tomorrow, 52.5% would be somewhat or very anxious. Of those who chose gel, 63.47% would be more or much more willing to return for recall visits if the gel were available. Using multivariate logistic regression, concern about pain and anxiety associated with needles were the only statistically significant characteristics associated with anaesthetic preference. Concern about pain and anxiety associated with needles dominates preferences for dental anaesthesia. The overwhelming preference for a non-injectable anaesthetic reveals a strong clinical need for such alternatives.


Manipulations of silver nanowires in a droplet on a low-frequency ultrasonic stage.
In this work, we report the use of a low-frequency circular ultrasonic stage to form a circular spot of silver nanowires (AgNWs) at the stage center and to radially align AgNWs on the stage surface. The manipulations are implemented within an AgNW suspension droplet at the center of the ultrasonic stage. The ultrasonic stage (50.8 mm diameter, 3.5 mm thick) operates at a flexural vibration mode symmetric about its center and has a vibration peak at the center. The AgNW suspension is formed of deionized water with AgNWs dispersed in it. The operating frequency of the ultrasonic stage is 21.3 kHz; the AgNWs have diameter of 100 nm and length of approximately 30 μm. When the ultrasonic stage vibrates properly, AgNWs on the substrate surface in the droplet may move to the stage center and form a spot or rotate to the radial direction and align radially. The spot diameter and thickness are several hundred micrometers and several micrometers, respectively. The rotation speed of a single AgNW can be up to 31°/min when the vibration velocity of the stage center is 42 mm/s (0-p) for a 40-μL droplet. After the droplet dries out by natural evaporation without ultrasound, the spot and radial alignment have little change in the size and pattern. Principle analyses show that the spot formation and radial alignment of AgNWs are caused by the acoustic streaming in the radial direction in the droplet.


Fertility and polarized cell growth depends on eIF5A for translation of polyproline-rich formins in Saccharomyces cerevisiae.
eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a proline-rich formin involved in polarized growth during shmoo formation. Our data indicate that translation of the polyproline motifs in Bni1 is eIF5A dependent and this translation dependency is lost upon deletion of the polyprolines. Moreover, an exogenous increase in Bni1 protein levels partially restores the defect in shmoo formation seen in eIF5A mutants. Overall, our results identify eIF5A as a novel and essential regulator of yeast mating through formin translation. Since eIF5A and polyproline formins are conserved across species, our results also suggest that eIF5A-dependent translation of formins could regulate polarized growth in such processes as fertility and cancer in higher eukaryotes.


A Longitudinal Investigation of Posttraumatic Growth and Quality of Life in Liver Transplant Recipients.
What does it mean to adjust to a liver transplant? Quality of life research has offered an impairment model, defining adjustment as the absence of diagnosed psychological disorder or of limitations in physical functioning. Recently emerging research on posttraumatic growth testifies the prevalence of positive life changes following the life-threatening illnesses. The present study aimed to verify the presence of the posttraumatic growth process in liver transplant patients and its relationship with traditional quality of life. The research was a longitudinally descriptive study. A sample of 233 liver transplant patients were assessed with the Posttraumatic Growth Inventory and the Functional Assessment of Chronic Illness Therapy General. Over 50% of patients showed moderate-high levels in all dimensions of the Posttraumatic Growth Inventory. Further posttraumatic growth is correlated with the functional and social dimensions of quality of life construct and not with physical and emotional functioning. These results confirmed that posttraumatic growth is related to a different definition of well-being than the one traditionally used in the assessment of quality of life. Adjustment to liver transplant is a complex and systemic process, which requires a multidisciplinary approach to be able to support and encourages adaptation through all the needed functional elements. An interesting perspective is offered by the narrative medicine approach, that highlighted the importance to pay specific attention to the words and expression used by patients related to changes in life and not only to traditional words reporting physical status.


The CREATE Strategy for Intensive Analysis of Primary Literature Can Be Used Effectively by Newly Trained Faculty to Produce Multiple Gains in Diverse Students.
The CREATE (Consider Read, Elucidate the hypotheses, Analyze and interpret the data, and Think of the next Experiment) strategy aims to demystify scientific research and scientists while building critical thinking, reading/analytical skills, and improved science attitudes through intensive analysis of primary literature. CREATE was developed and piloted at the City College of New York (CCNY), a 4-yr, minority-serving institution, with both upper-level biology majors and first-year students interested in science, technology, engineering, and mathematics. To test the extent to which CREATE strategies are broadly applicable to students at private, public, research-intensive, and/or primarily undergraduate colleges/universities, we trained a cohort of faculty from the New York/New Jersey/Pennsylvania area in CREATE pedagogies, then followed a subset, the CREATE implementers (CIs), as they taught all or part of an existing course on their home campuses using CREATE approaches. Evaluation of the workshops, the CIs, and their students was carried out both by the principal investigators and by an outside evaluator working independently. Our data indicate that: intensive workshops change aspects of faculty attitudes about teaching/learning; workshop-trained faculty can effectively design and teach CREATE courses; and students taught by such faculty on multiple campuses make significant cognitive and affective gains that parallel the changes documented previously at CCNY.


Benign breast disease and the risk of breast cancer.
Benign breast disease is an important risk factor for breast cancer. We studied a large group of women with benign breast disease to obtain reliable estimates of this risk. We identified all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991. Breast-cancer events were obtained from medical records and questionnaires. To estimate relative risks, we compared the number of observed breast cancers with the number expected on the basis of the rates of breast cancer in the Iowa Surveillance, Epidemiology, and End Results registry. We followed 9087 women for a median of 15 years. The histologic findings were nonproliferative lesions in 67 percent of women, proliferative lesions without atypia in 30 percent, and atypical hyperplasia in 4 percent. To date, 707 breast cancers have developed. The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia. Risk factors for breast cancer after the diagnosis of benign breast disease include the histologic classification of a benign breast lesion and a family history of breast cancer.


Influence of blanching and grinding process with hot water on beany and non-beany flavor in soymilk.
A total of 8 beany odor-active compounds and 4 non-beany aroma-active compounds of traditional soymilk were identified through dynamic headspace dilution analysis (DHDA) and gas chromatography-olfactometry-mass spectrometry (GC-O-MS). To eliminate the beany flavors, soymilk was processed with hot water blanching and grinding for 2, 4, 6, 8, and 10 min with a temperature between 80 and 100 °C. A total of 5 beany odor-active compounds and 3 non-beany aroma-active compounds of this soymilk were analyzed by headspace solid phase microextraction (HS-SPME). As a result, lipoxygenase (LOX) activity gradually decreased by hot water treatment with time, and with the decrease of Lox activity, the 5 beany odor-active compounds and 3 non-beany aroma-active compounds were significantly decreased. However, the reduction in non-beany flavor compounds was smaller than for beany odor compounds. Therefore, a balance between beany and non-beany flavors can be reached in soymilk. When the soaked soybeans were blanched and ground with hot water for 2 to 6 min, the LOX activity was between 38% and 57% of the beginning activity. For these processing times, the non-beany compounds could be largely maintained. The ratio of the total peak area of the 3 non-beany aroma compounds and 5 beany flavor compounds was between 0.07 and 0.12, and the sensory scores of the aromas were higher than that of the off-flavors. Practical Application: Beany flavors in soymilk could be reduced with hot water blanching and grinding at temperature above 80 °C. However, the treatment of hot water blanching affected the non-beany aromas of soymilk. A suitable blanching and grinding time is necessary to achieve a balance of soymilk flavors.


Infant and child mortality in the Netherlands 1935-47 and changes related to the Dutch famine of 1944-45: A population-based analysis.
Precise estimates of the impact of famine on infant and child mortality are rare due to lack of representative data. Using vital statistics reports on the Netherlands for 1935-47, we examine the impact of the Dutch famine (November 1944 to May 1945) on age-specific mortality risk and cause of death in four age groups (stillbirths, <1 year, 1-4, 5-14) in the three largest famine-affected cities and the remainder of the country. Mortality during the famine is compared with the pre-war period January 1935 to April 1940, the war period May 1940 to October 1944, and the post-war period June 1945 to December 1947. The famine's impact was most visible in infants because of the combined effects of a high absolute death rate and a threefold increase in proportional mortality, mostly from gastrointestinal conditions. These factors make infant mortality the most sensitive indicator of famine severity in this setting and a candidate marker for comparative use in future studies.


[Effect of titanium dioxide nano- and microparticles on the values of the micronucleus test using human blood lymphocytes in culture].
The activity of the nano- and microparticles of titanium dioxide (TD) given in doses of 1.6, 40.0, and 500 microg/ml was studied in the cytochalasin B block micronucleus test with blood cells from two donors. It was shown that nano-DT in doses of 1.6 and 40 microg/ml was more active than micro-DT in inducing micronuclei and nucleoplasmic bridges, asymmetric cell division, and accelerated cell proliferation. Some differences in individual sensitivity to TD between donor blood cultures were due to an inverse trend in the association between the indicators of genomic damage and apoptosis. The new nuclear morphometry test that had developed to screen genotoxic effects and used in this study for the first time revealed a nano-DT dose-depended increase in the asymmetry of nuclei in the binucleated cells in the cultures of both blood donors, the morphometric effects being directly correlated with the values of cytogenetic analysis.


Targeted molecular therapies in thyroid carcinoma.
Thyroid cancer incidence has significantly increased in the last three decades and many patients seek medical attention for its treatment every year. Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15% of the cases presenting disease persistence or recurrence after initial treatment. Medullary thyroid carcinoma has a worse prognosis, especially in patients with diffused cancers at the time of initial surgery. Traditional treatment options for persistent or recurrent disease include additional surgery, radioiodine treatment and TSH-suppression in DTC patients; external beam radiotherapy, and cytotoxic chemotherapy, often have low efficacy and many patients with advanced disease ultimately die. In the last two decades many of the molecular events involved in cancer formation have been uncovered. This knowledge has prompted the development of novel therapeutic strategies mainly based on the inhibition of key molecular mediators of the tumorigenic process. In particular the class of small-molecule tyrosine kinase inhibitors was enriched by many compounds that have reached clinical trials and in some cases have had approval for clinical use in specific cancers. Many of these compounds entered clinical trials also for locally advanced or metastatic thyroid carcinomas showing very promising results.


Resistive pulse sensing of magnetic beads and supraparticle structures using tunable pores.
Tunable pores (TPs) have been used for resistive pulse sensing of 1 μm superparamagnetic beads, both dispersed and within a magnetic field. Upon application of this field, magnetic supraparticle structures (SPSs) were observed. Onset of aggregation was most effectively indicated by an increase in the mean event magnitude, with data collected using an automated thresholding method. Simulations enabled discrimination between resistive pulses caused by dimers and individual particles. Distinct but time-correlated peaks were often observed, suggesting that SPSs became separated in pressure-driven flow focused at the pore constriction. The distinct properties of magnetophoretic and pressure-driven transport mechanisms can explain variations in the event rate when particles move through an asymmetric pore in either direction, with or without a magnetic field applied. Use of TPs for resistive pulse sensing holds potential for efficient, versatile analysis and measurement of nano- and microparticles, while magnetic beads and particle aggregation play important roles in many prospective biosensing applications.


Monocytes express Fas ligand upon CD4 cross-linking and induce CD4+ T cells apoptosis: a possible mechanism of bystander cell death in HIV infection.
Recent evidence indicates that death of uninfected lymphocytes by apoptosis plays an important role in the immunopathogenesis of HIV infection. We have previously demonstrated that CD4 cross-linking (CD4XL) performed in PBMC results in induction of T cell apoptosis in an accessory cell-dependent manner. In this study, we have investigated the roles of Fas interaction with its ligand (FasL) and of accessory cells in the CD4XL model of T cell apoptosis mediated by the anti-CD4 mAb Leu3a- or HIV-1 envelope protein g120. Here, we provide evidence that CD4XL-induced CD4+ T cell apoptosis is Fas-FasL interaction dependent and that monocytes play a critical role in inducing T cell apoptosis. We show that CD4XL-induced T cell apoptosis is blocked by the addition of soluble Fas or by anti-FasL mAb NOK-1; depletion of monocytes from PBMC, but not of CD19+ cells or CD8+ cells, abrogates CD4XL-induced T cell apoptosis. Conversely, addition of monocytes to purified CD4+ T cells augments CD4XL-induced apoptosis. In purified monocytes, CD4XL results in FasL expression; in purified CD4+ T cells, however, CD4XL upregulates Fas but not FasL expression. These findings underscore the important role of monocytes in HIV disease pathogenesis and firmly support the notion of CD4XL as a potent mechanism for inducing bystander cell death.


Advances in Cardiac Computed Tomography Functional Imaging Technology.
Cardiovascular disease (CVD) is the leading cause of death among patients in China, and cardiac computed tomography (CT) is one of the most commonly used examination methods for CVD. Coronary artery CT angiography can be used for the morphologic evaluation of the coronary artery. At present, cardiac CT functional imaging has become an important direction of development of CT. At present, common CT functional imaging technologies include transluminal attenuation gradient, stress dynamic CT myocardial perfusion imaging, and CT-fractional flow reserve. These three imaging modes are introduced and analyzed in this review.


Calculation of porosity and osteonal cement line effects on the effective fracture toughness of cortical bone in longitudinal crack growth.
Based on the microscopic analyses of cracks and correlational studies demonstrating evidence for a relationship between fracture toughness and microstructure of cortical bone, an equation was derived for bone fracture toughness in longitudinal crack growth, using debonding at osteonal cement lines and weakening effect of pores as main crack mechanisms. The correlation between the measured and predicted values of fracture toughness was highly significant but weak for a single optimal value of matrix to cement line fracture toughness ratio. Using fracture toughness values and histomorphometrical parameters from an available data set, matrix to cement line fracture toughness ratio was calculated for human femoral bone. Based on these calculations it is suggested that the effect of an osteon on fracture toughness will depend on the cement line's ability to compensate for the pore in an osteon. Matrix to cement line fracture toughness ratio significantly increased with increasing age, suggesting that the effectiveness of osteons in energy absorption may be reduced in the elderly due to a change in cement line properties.


Characteristics of multiple early gastric cancer and gastric high-grade intraepithelial neoplasia.
This study evaluated the clinical characteristics of multiple early gastric cancer (MEGC) and high-grade intraepithelial neoplasia (HGIN) treated by endoscopic submucosal dissection. The clinical profiles of 23 patients with MEGC treated by endoscopic submucosal dissection from January 2008 to June 2019 at the Fujian Provincial Hospital or Fujian Provincial Hospital South Branch were analyzed. The following information was extracted from clinical records: general data, preoperative conditions, and pathological data of each lesion after surgery. In total, 23 patients with MEGC or HGIN were evaluated (average age 64 ± 6 years, 17 (73.9%) males). MEGC and HGIN accounted for 4.9 percent of all cases, in which 19 (4.1%) were synchronous multiple cancers and 4 (0.8%) cases were metachronous multiple cancers. Lesions of synchronous and metachronous MEGC groups did not differ in age, sex, smoking history, alcohol consumption, family history of tumors, Helicobacter pylori infection, mucosal background atrophy, or intestinal metaplasia (P > .05). The vertical locations of primary and secondary lesions of MEGC were correlated (R = 0.395, P = .034). The primary and secondary lesions of MEGC shared the same macroscopic subtype (R = 0.590, P = .015), infiltration depth (R = 0.455, P = .014), and pathological subtype (R = 0.736, P < .001). MEGC and HGIN were located in close proximity. Pathologic types tended to be low-grade malignancies. The macroscopic type, histology type, and infiltration depth of the 2 lesions were significantly correlated. When detecting early gastric cancer, we should inspect the stomach and carefully consider the pathological characteristics, to improve the diagnosis of MEGC.


Dietitian-observed macronutrient intakes of young skill and team-sport athletes: adequacy of pre, during, and postexercise nutrition.
Sports nutrition experts recommend that team-sport athletes participating in intermittent high-intensity exercise for ≥1 hr consume 1-4 g carbohydrate/kg 1-4 hr before, 30-60 g carbohydrate/hr during, and 1-1.2 g carbohydrate/kg/hr and 20-25 g protein as soon as possible after exercise. The study objective was to compare observed vs. recommended macronutrient intake of competitive athletes under free-living conditions. The dietary intake of 29 skill/team-sport athletes (14-19 y; 22 male, 7 female) was observed at a sports training facility by trained registered dietitians for one 24-hr period. Dietitians accompanied subjects to the cafeteria and field/court to record their food and fluid intake during meals and practices/competitions. Other dietary intake within the 24-hr period (e.g., snacks during class) was accounted for by having the subject take a picture of the food/fluid and completing a log. For male and female athletes, respectively, the mean ± SD (and percent of athletes meeting recommended) macronutrient intake around exercise was 1.4 ± 0.6 (73%) and 1.4 ± 1.0 (57%) g carbohydrate/kg in the 4 hr before exercise, 21.1 ± 17.2 (18%) and 18.6 ± 13.2 (29%) g carbohydrate/hrr during exercise, 1.4±1.1 (68%) and 0.9± 1.0 (43%) g carbohydrate/kg and 45.2 ± 36.9 (73%) and 18.0 ± 21.2 (43%) g protein in the 1 hr after exercise. The male athletes' carbohydrate and protein intake more closely approximated recommendations overall than that of the female athletes. The most common shortfall was carbohydrate intake during exercise, as only 18% of male and 29% of female athletes consumed 3060 g carbohydrate/hr during practice/competition.


Conserved and differential effects of dietary energy intake on the hippocampal transcriptomes of females and males.
The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control), 20% caloric restriction (CR), 40% CR, intermittent fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1alpha and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability.


Direct observation of the fourth MLCT triplet state in ruthenium(II) tris(2,2'-bipyridine).
The luminescence properties of ruthenium(ii) tris(2,2'-bipyridine) have been recorded in butyronitrile solution and in a transparent KBr disk over a reasonable temperature range. In solution, spectral curve fitting routines indicate that emission arises solely from an ensemble of triplet states, each of which is of Metal-to-Ligand, Charge-Transfer (MLCT) character and of closely comparable energy. At ambient temperature, dual emission is observed for the KBr disk and interpreted in terms of luminescence from both the ensemble and the fourth MLCT triplet state that lies at slightly higher energy. Relative reorganisation energies, energies, Huang-Rhys factors and radiative rate constants have been calculated for the two emissive states. It is confirmed that the fourth MLCT triplet state possesses more singlet character than the ensemble.


Comprehensive molecular pharmacology screening reveals potential new receptor interactions for clinically relevant opioids.
Most clinically used opioids are thought to induce analgesia through activation of the mu opioid receptor (MOR). However, disparities have been observed between the efficacy of opioids in activating the MOR in vitro and in inducing analgesia in vivo. In addition, some clinically used opioids do not produce cross-tolerance with each other, and desensitization produced in vitro does not match tolerance produced in vivo. These disparities suggest that some opioids could be acting through other targets in vivo, but this has not been comprehensively tested. We thus screened 9 clinically relevant opioids (buprenorphine, hydrocodone, hydromorphone, morphine, O-desmethyl-tramadol, oxycodone, oxymorphone, tapentadol, tramadol) against 9 pain-related receptor targets (MOR, delta opioid receptor [DOR], kappa opioid receptor [KOR], nociceptin receptor [NOP], cannabinoid receptor type 1 [CB1], sigma-1 receptor [σ1R], and the monoamine transporters [NET/SERT/DAT]) expressed in cells using radioligand binding and functional activity assays. We found several novel interactions, including monoamine transporter activation by buprenorphine and σ1R binding by hydrocodone and tapentadol. Tail flick anti-nociception experiments with CD-1 mice demonstrated that the monoamine transporter inhibitor duloxetine selectively promoted buprenorphine anti-nociception while producing no effects by itself or in combination with the most MOR-selective drug oxymorphone, providing evidence that these novel interactions could be relevant in vivo. Our findings provide a comprehensive picture of the receptor interaction profiles of clinically relevant opioids, which has not previously been performed. Our findings also suggest novel receptor interactions for future investigation that could explain some of the disparities observed between opioid performance in vitro and in vivo.


Pooling of prognostic studies in cancer of the pancreatic head and periampullary region: the Triple-P study. Triple-P study group.
Development of a prognostic tool for patients with unresectable pancreatic cancer to distinguish between with low or high probabilities of survival 3 to 9 months after diagnosis. Data about individual patients from five studies were pooled. A multivariate proportional hazards model with time-dependent covariates was developed, including age, sex, and metastases. An extended model was developed on a subset of patients, including weight loss, pain, and jaundice at diagnosis. Multicentre study, The Netherlands, Norway, USA, UK, and Canada. 1020 patients with unresectable pancreatic cancer. Prediction of prognosis. Patients with metastases, pain, or weight loss at diagnosis had a significantly poorer prognosis than the others. Older men had a worse prognosis than younger men, while older women had a better prognosis than younger ones. Patients with jaundice had a relatively good prognosis. Differences in survival among the studies were incorporated in a prognostic score chart. The prognostic score chart can be used to select patients with relatively low expectation of survival for endoscopic palliation, and patients with relatively high expectation for surgical palliation.