Parental Folate Deficiency Inhibits Proliferation and Increases Apoptosis of Neural Stem Cells in Rat Offspring: Aggravating Telomere Attrition as a Potential Mechanism.
The effect of maternal folate status on the fetal central nervous system (CNS) is well recognized, while evidence is emerging that such an association also exists between fathers and offspring. The biological functions of telomeres and telomerase are also related to neural cell proliferation and apoptosis. The study aimed to investigate the effect of parental folate deficiency on the proliferation and apoptosis of neural stem cells (NSCs) in neonatal offspring and the role of telomeres in this effect. In this study, rats were divided into four groups: maternal folate-deficient and paternal folate-deficient diet (D-D) group; maternal folate-deficient and paternal folate-normal diet (D-N) group; maternal folate-normal and paternal folate-deficient diet (N-D) group; and the maternal folate-normal and paternal folate-normal diet (N-N) group. The offspring were sacrificed at postnatal day 0 (PND0), and NSCs were cultured from the hippocampus and striatum tissues of offspring for future assay. The results revealed that parental folate deficiency decreased folate levels, increased homocysteine (Hcy) levels of the offspring's brain tissue, inhibited proliferation, increased apoptosis, shortened telomere length, and aggravated telomere attrition of offspring NSCs in vivo and in vitro. In vitro experiments further showed that offspring NSCs telomerase activity was inhibited due to parental folate deficiency. In conclusion, parental folate deficiency inhibited the proliferation and increased apoptosis of offspring NSCs, maternal folate deficiency had more adverse effects than paternal, and the mechanisms may involve the telomere attrition of NSCs.


[Myelofibrosis in a benzene-exposed cleaning worker].
Long-term exposure to benzene has been associated with several blood malignancies, including aplastic anemia, myeloproliferative neoplasms, and different leukemias. We present a case of primary myelofibrosis in a 59-year-old woman who worked as a cleaner at a car dealership and automobile mechanic shop. For 25 years, she used gasoline as a degreaser and solvent to clean engine parts, floors and work desks on a daily basis. She was referred by her primary care provider to the Occupational Health Unit of Barcelona to assess whether her illness was work-related. Review of her job history and working conditions revealed chronic exposure to benzene in the absence of adequate preventive measures. An association between benzene exposure and myeloproliferative disease was established, suspicious for an occupational disease.


[Investigation of micro-aqueous covalent immobilization of horseradish peroxidase by "conformation memory"].
We has studied the feasibility of preventing protein from denature during covalent immobilization by "conformation memory", which was achieved by freeze-drying under enzyme active conformation and cross-linked with carrier under micro-aqueous media (MAM). Horseradish peroxidase (HRP) and chitosan beads have been used as the model enzyme and carrier. The MAM consisted of 99% dioxane and 1% water. We compared the immobilized HRP under MAM with that under traditional aqueous solvent, found that the optimum temperature of both was raised to 60 degrees C, and the optimum pH was 6.5. However, the MAM-immobilized HRP had shown less activity loss during usage and six times higher activity than that immobilized under aqueous solvent. After 30 min incubation at 70 degrees C, the MAM-immobilized HRP remained 75.42% activity while the aqueous-media-immobilized enzyme only 15.4%. The MAM-immobilized HRP has shown a better operation stability with 77.69% residue activity after 5 times of repeat operation while the aqueous-media-immobilized enzyme only 16.67%. In addition, the MAM-immobilized HRP had also shown more advantages when used in phenol removal. We constructed enzyme electrodes (CS-HRP-SWCNTs/Au) to further display the different properties of the two immobilized HRP. MAM-immobilized HRP-electrode has shown two times stronger response signal to H2O2 than that immobilized under aqueous media, which indicated a better enzyme activity of MAM-immobilized HRP. Our research demonstrated that the conformation memory, to some extent, did contribute to preventing protein from denaturing when use HRP as a model, and it is feasible to immobilize enzyme by covalent cross-linking method under micro-aqueous media.


Integrated motor cortical control of task-related muscles during pointing in humans.
A large body of compelling but indirect evidence suggests that the motor cortex controls the different forelimb segments as a whole rather than individually. The purpose of this study was to obtain physiological evidence in behaving human subjects on the mode of operation of the primary motor cortex during coordinated movements of the forelimb. We approached this problem by studying a pointing movement involving the shoulder, elbow, wrist, and index finger as follows. Focal transcranial magnetic stimulation (TMS) was used to measure the input-output (I/O) curves-a measure of the corticospinal pathway excitability-of proximal (anterior deltoid, AD, and triceps brachii, TB) and distal muscles (extensor carpi radialis, ECR, and first dorsal interosseus, 1DI) during isolated contraction of one of these muscles or during selective co-activation with other muscles involved in pointing. Compared to an isolated contraction of the ECR, the plateau-level of the ECR sigmoid I/O curve increased markedly during co-activation with the AD while pointing. In contrast, the I/O curve of AD was not influenced by activation of the more distal muscles involved in pointing. Moreover, the 1DI I/O curve was not influenced by activation of the more proximal muscles. Three arguments argue for a cortical site of facilitation of ECR motor potentials. First, ECR motor potentials evoked by a near threshold TMS stimulus were facilitated when the AD and ECR were co-activated during pointing but not those in response to a near threshold anodal electrical stimulus. Second, the ECR H reflex was not found to be task dependent, indicating that the recruitment gain of the ECR alpha-motoneuron pool did not differ between tasks. Finally, in comparison with an isolated ECR contraction, intracortical inhibition tested at the ECR cortical site was decreased during pointing. These results suggest that activation of shoulder, elbow, and wrist muscles involved in pointing appear to involve, at least in part, common motor cortical circuits. In contrast, at least in the pointing task, the motor cortical circuits involved in activation of the 1DI appear to act independently.


Visualization of ultrasound induced cavitation bubbles using the synchrotron x-ray Analyzer Based Imaging technique.
Observing cavitation bubbles deep within tissue is very difficult. The development of a method for probing cavitation, irrespective of its location in tissues, would improve the efficiency and application of ultrasound in the clinic. A synchrotron x-ray imaging technique, which is capable of detecting cavitation bubbles induced in water by a sonochemistry system, is reported here; this could possibly be extended to the study of therapeutic ultrasound in tissues. The two different x-ray imaging techniques of Analyzer Based Imaging (ABI) and phase contrast imaging (PCI) were examined in order to detect ultrasound induced cavitation bubbles. Cavitation was not observed by PCI, however it was detectable with ABI. Acoustic cavitation was imaged at six different acoustic power levels and six different locations through the acoustic beam in water at a fixed power level. The results indicate the potential utility of this technique for cavitation studies in tissues, but it is time consuming. This may be improved by optimizing the imaging method.


Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field.
A number of important changes take place in the maternal uterine vasculature during the first few weeks of pregnancy resulting in increased blood flow to the intervillous space. Vascular endothelial and smooth muscle cells are lost from the spiral arteries and are replaced by fetal trophoblast cells. Failure of the vessels to remodel sufficiently is a common feature of pregnancy pathologies such as early pregnancy loss, intrauterine growth restriction and pre-eclampsia. There is evidence to suggest that some vascular changes occur prior to trophoblast invasion, however, in the absence of trophoblasts remodelling of the spiral arteries is reduced. Until recently our knowledge of these events has been obtained from immunohistochemical studies which, although extremely useful, can give little insight into the mechanisms involved. With the development of more complex in vitro models a picture of events at a cellular and molecular level is beginning to emerge, although some caution is required in extrapolating to the in vivo situation. Trophoblasts synthesise and release a plethora of cytokines and growth factors including members of the tumour necrosis factor family. Studies suggest that these factors may be important in regulating the remodelling process by inducing both endothelial and vascular smooth muscle cell apoptosis. In addition, it is evident from studies in other vascular beds that the structure of the vessel is influenced by factors such as flow, changes in the composition of the extracellular matrix, the phenotype of the vascular cells and the local immune cell environment. It is the aim of this review to present our current knowledge of the mechanisms involved in spiral artery remodelling and explore other possible pathways and cellular interactions that may be involved, informed by studies in the cardiovascular field.


Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids.
Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). "Mixed rhinitis" (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper-reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.


FoxO3a Regulates Inflammation-induced Autophagy in Odontoblasts.
FoxO3a is a member of FoxO transcription factor family that participates in the transcriptional regulation of autophagy. In this study we explored the anti-inflammatory function of FoxO3a-regulated autophagy in inflamed human dental pulp and lipopolysaccharide-treated mDPC6T cells. The expression of FoxO3a and autophagy markers in caries and pulpitis from human dental pulp were examined by immunohistochemistry and Western blot. We conducted in vitro studies by treating mDPC6T cells with lipopolysaccharide for various lengths of time. Next, we measured the nuclear translocation of FoxO3a by immunofluorescence and investigated the potential relationship between FoxO3a and autophagy after FoxO3a knockdown using small interfering RNA. The expression of FoxO3a and autophagy proteins was upregulated in the odontoblasts of human caries and pulpitis samples. In addition, we also observed that the enhanced nuclear translocation of FoxO3a was positively correlated with the progression of inflammation. The results of our in vitro study revealed that 6 hours of lipopolysaccharide treatment increased nuclear translocation of FoxO3a and activated autophagy in mDPC6T cells. We also observed that the knockdown of FoxO3a suppressed autophagy. Our data indicate that FoxO3a might play a role in autophagy activation and the maintenance of intracellular homeostasis in inflamed odontoblasts.


Rare diseases research: expanding collaborative translational research opportunities.
Extensive public-private partnerships, including the National Institutes of Health (NIH) and the rare diseases community, which is seeing a renewed industry interest in smaller niche markets, have resulted in an increase of interventions for rare diseases. Significant collaborative efforts are required among the pharmaceutical industry, foundations, patient-advocacy groups, academic and government investigators and funding programs, regulatory scientists, and reimbursement agencies to meet the unmet diagnostic and treatment needs for approximately 25 million people in the United States with 7,000 rare diseases. The expanding role and outreach activities of patient-advocacy groups have increased public awareness. In the United States, a rare disease is defined as a disorder or condition with a prevalence of <200,000 people. In 2011, the NIH provided >$3.5 billion for rare diseases research, including $750 million for orphan product development activities, nearly 11.4% of the NIH research budget. Several research institutes and centers of the NIH, including the National Center for Advancing Translational Sciences, have initiated varied translational research efforts to address the absence of preclinical and clinical data required for regulatory review purposes. Clinicians can expect to see significant increases in requests from patients and their families to participate in patient registries and natural history or observational studies to gather specific information from a larger pool of patients on the progression of the disease or response to treatments. An expanding emphasis on rare diseases provides hope for the millions of patients with rare diseases.


Human lymphocyte colony formation in agar culture: cell phenotype studies on individual colonies indicate a polyclonal origin of such colonies.
Monoclonal origin of human lymphocyte colonies grown in agar culture under mitogenic stimulation is still disputed. To solve this question we used different markers: we failed with the G6PD technic and with the successive staining for X and Y chromosomes on individual colonies. Therefore, individual colonies were investigated for the presence of different cell types using membrane receptor identification and cytochemistry. At different stages of the colony formation, presence of a macrophage surrounded by lymphocytes, of a mixture of T cells and B cells, plasma cells and c.Ig negative cells, in the same colony was demonstrated. The mixture of cells from different lineages in individual colonies indicated a polyclonal origin of such colonies, the capacity for the cells to migrate in a short distance, and the involvement of cell-cell contact throughout the colony formation. Human lymphocyte colony formation appears as a new technic for the study of cellular cooperation.


Giant Orbital-to-Spin Conversion for Efficient Current-Induced Magnetization Switching of Ferrimagnetic Insulator.
It has long been believed that the attachment of two heavy metals such as Ta and Pt with opposite spin Hall angles results in a weakened net torque generation efficiency in magnetization switching devices. Here, we report a giant orbital-to-spin conversion in Ta/Pt/Tm3Fe5O12 (TmIG) heterostructures. We show that the torque generation efficiency is enhanced by an order of magnitude in the Ta/Pt/TmIG trilayer compared to that in the Pt/TmIG bilayer. This enhancement is further evidenced by the fact that the critical current density for the magnetization switching of the Ta/Pt/TmIG is an order of magnitude smaller than that of the Pt/TmIG. It is found that the orbital current generated from Ta through the orbital Hall effect (OHE) is converted to the spin current in the interior of Pt. Our discovery offers an extraordinary approach to enhance the torque generation for magnetization switching of insulators and provides an important piece of information for orbitronics.


On the structure and synthesis of neuroprotectin D1, a novel anti-inflammatory compound of the docosahexaenoic acid family.
Potato tuber lipoxygenase was shown to convert 17(S)-hydro(pero)xydocasahexaenoic acid in 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid [10,17(S)-diHDHA] which was formed apparently through a double lipoxygenation mechanism. No traces of 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13E,15Z,19Z-enoic acid were found among the reaction products. It is very likely that a described earlier "neuroprotectin D1" [or "10,17(S)docosatriene"], a novel and potent anti-inflammatory compound derived from docosahexaenoic acid, was, in fact, 10,17(S)-dihydroxydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid formed through a double lipoxygenation mechanism instead of a previously thought epoxidation/isomerization mechanism.


Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling.
Lead (Pb(2+)) exposure is known to affect presynaptic neurotransmitter release in both in vivo and cell culture models. However, the precise mechanism by which Pb(2+) impairs neurotransmitter release remains unknown. In the current study, we show that Pb(2+) exposure during synaptogenesis in cultured hippocampal neurons produces the loss of synaptophysin (Syn) and synaptobrevin (Syb), two proteins involved in vesicular release. Pb(2+) exposure also increased the number of presynaptic contact sites. However, many of these putative presynaptic contact sites lack Soluble NSF attachment protein receptor complex proteins involved in vesicular exocytosis. Analysis of vesicular release using FM 1-43 dye confirmed that Pb(2+) exposure impaired vesicular release and reduced the number of fast-releasing sites. Because Pb(2+) is a potent N-methyl-D-aspartate receptor (NMDAR) antagonist, we tested the hypothesis that NMDAR inhibition may be producing the presynaptic effects. We show that NMDAR inhibition by aminophosphonovaleric acid mimics the presynaptic effects of Pb(2+) exposure. NMDAR activity has been linked to the signaling of the transsynaptic neurotrophin brain-derived neurotrophic factor (BDNF), and we observed that both the cellular expression of proBDNF and release of BDNF were decreased during the same period of Pb(2+) exposure. Furthermore, exogenous addition of BDNF rescued the presynaptic effects of Pb(2+). We suggest that the presynaptic deficits resulting from Pb(2+) exposure during synaptogenesis are mediated by disruption of NMDAR-dependent BDNF signaling.


Detection of Histamine in Fish and Fishery Products in Osaka Prefecture (Fiscal 2015 Report).
Histamine food poisoning is caused by ingestion of spoiled fish containing high levels of histamine. This paper reports cases in which histamine was detected in Osaka prefecture in fiscal year 2015 in a survey of fish and fishery products on the market and the food poisoning. A suspected case of histamine food poisoning was also evaluated to investigate the cause and minimize further problems. Histamine in food was separated on SPE cartridge columns, and analyzed after derivatization with fluorescamine by means of HPLC-FL. Histamine was detected in some fishery products on the market and in food that had caused poisoning. The samples in which histamine was detected were semi-dried whole round herring (Urumeiwashi-maruboshi), mackerel (Saba) and sardine dumpling (Iwashi-tsumire). These foods were the main causes of histamine food poisoning according to the report of the Ministry of Health, Labour and Welfare, Government of Japan.


[The influence on pedicle flap blood supply and necrosis rate of plastic displacement with pentoxifylline and dextran 40].
Using a standardized procedure we have experimented on rats in order to examine the rate of necrosis in pedicle flaps in conjunction with 3,7-dimethyl-1-(5-oxo-hexyl)-xanthine (pentoxifyline, Trental) and dextran 40. Compared with the control group and that treated with dextran 40 the group treated with Trental showed significant decrease in necroses. The influence of drugs on blood supply demonstrated in this srudy as being significant is discussed.


Rapid expression of IL-1beta by intestinal epithelial cells in vitro.
Intestinal epithelial cells have been shown to produce IL-1beta in vivo. This gene expression is rapid and precedes most determinants of inflammation, suggesting a pivotal role for IL-1beta in the early events leading to inflammation. To better understand the mechanisms leading to this IL-1beta production, we have developed an in vitro model system employing a nontransformed intestinal epithelial cell line that does not constitutively express IL-1beta. Following detachment, these cells rapidly expressed IL-1beta mRNA. This expression was enhanced, but not induced, by LPS. IL-1beta protein was detected by immunoprecipitation in the culture medium from passaged IEC-18 but not intracellularly, suggesting an efficient secretion of the molecule following induction. Interestingly, culture supernatants from passaged cells were without IL-1 bioactivity, suggesting the presence of an inhibitor as well. RT-PCR and Western blot analysis showed expression of IL-1RII by IEC-18 following detachment, possibly explaining the observed lack of bioactivity. These results indicate a novel pathway for IL-1beta production and suggest that proinflammatory effects of IEC-derived IL-1 may be modulated by the simultaneous production of IL-1 antagonists.


Comparison of 18-Month Outcomes of Ambulatory Patients With Reduced (≤40%) Left Ventricular Ejection Fraction Treated in a Community-Based, Dedicated Heart Failure Clinic Versus Treated Elsewhere.
We sought to examine the management and outcomes of ambulatory patients with heart failure and reduced ejection fraction in a community-based, dedicated clinic. Patients with left ventricular ejection fraction (LVEF) ≤40% were actively solicited to attend a community-based, dedicated clinic. Eligible patients who chose to decline constituted our control group. Of 552 patients with LVEF ≤40% (median age 73 years and median LVEF 35%), 304 (55%) agreed to attend the clinic. Patients with worse New York Heart Association class were more likely to attend the clinic (odds ratio 2.07 [1.45, 2.95], p <0.001), whereas women were more likely to decline (odds ratio 0.63 [0.42, 0.93], p <0.022). During 18 months of follow-up, patients in the dedicated clinic significantly improved their functional capacity (56% New York Heart Association 3 to 4 at baseline vs 27% at follow-up, p <0.001) and LVEF (35% [interquartile range 25, 35] at baseline vs 35% (interquartile range 30, 40) at follow-up, p <0.001). In comparison with patients managed routinely, patients treated in a dedicated clinic achieved better guideline-recommended pharmacological treatment (65% vs 85% receiving β blockers, p <0.001, 65% vs 82% receiving renin-angiotensin inhibitors, p = 0.0006, 31% vs 45% receiving mineralocorticoid receptor antagonists, p <0.001). During follow-up, electrical device implantation was similar (6% vs 7% of dedicated-HF-clinic patients, p = 0.700). Furthermore, overall survival was better in patients treated in the clinic (log rank p = 0.0006), even after censoring the first 4 months to account for potential bias (log rank p = 0.0232). In conclusion, management in a community-based, dedicated clinic compared with routine management was associated with augmented guideline-recommended treatment and improved survival.


Chimeric, infectious, and stable virus transcripts to study RNA silencing in "dark green" islands.
Dark green islands (DGIs) form in some plant virus infections as areas that are resistant to infection. This resistance has been demonstrated to act through a sequence-specific, RNA degradation mechanism termed RNAi. In addition to the virus that induces the initial DGI, a second, infectious virus transcript carrying additional sequence of the initial virus can be used to dissect the RNAi mechanism of DGIs. The methods used to create stable, infectious transcripts that can carry heterologous sequences are described.


The neuron-restrictive silencer element: a dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain.
The neuron-restrictive silencer element (NRSE) has been identified in several neuronal genes and confers neuron specificity by silencing transcription in nonneuronal cells. NRSE is present in the promoter of the neuronal nicotinic acetylcholine receptor beta2-subunit gene that determines its neuron-specific expression in the nervous system. Using transgenic mice, we show that NRSE may either silence or enhance transcription depending on the cellular context within the nervous system. In vitro in neuronal cells, NRSE activates transcription of synthetic promoters when located downstream in the 5' untranslated region, or at less than 50 bp upstream from the TATA box, but switches to a silencer when located further upstream. In contrast, in nonneuronal cells NRSE always functions as a silencer. Antisense RNA inhibition shows that the NRSE-binding protein REST contributes to the activation of transcription in neuronal cells.


Rheological characterization of in situ cross-linkable hyaluronan hydrogels.
This report investigates the rheological properties of cross-linked, thiol-functionalized HA (HA-DTPH) hydrogels prepared by varying the concentration and molecular weight (MW) of the cross-linker, poly(ethylene glycol) diacrylate (PEGDA). Hydrogels were subsequently cured for either short-term (hours) or long-term (days) and subjected to oscillatory shear rheometry (OSR). OSR allows the evaluation and comparison of the shear storage moduli (G'), an index of the total number of effective cross-links formed in the hydrogels. While the oscillatory time sweep monitored the evolution of G' during in situ gelation, the stress and frequency sweeps measured the G' of preformed and subsequently cured hydrogels. From stress sweeps, we found that, for the hydrogels, G' scaled linearly with PEGDA concentration and was independent of its MW. Upon comparison with the classical Flory's theory of elasticity, stress sweep tests on short-term cured hydrogels revealed the simultaneous, but gradual, formation of spontaneous disulfide cross-links in the hydrogels. Results from time and frequency sweeps suggested that the formation of a stable, three-dimensional network depended strictly on PEGDA concentration. Results from the equilibrium swelling of hydrogels concurred with those obtained from oscillatory stress sweeps. Such a detailed rheological characterization of our HA-DTPH-PEGDA hydrogels will aid in the design of biomaterials targeted for biomedical or pharmaceutical purposes, especially in applications involving functional tissue engineering.


Long-term effectiveness of preserved celiac branch of vagal nerve after Roux-en-Y reconstruction in laparoscopy-assisted distal gastrectomy.
The aim of this retrospective cohort study was to clarify the effectiveness of preserving the celiac branch (CB) of the vagal trunk after the Roux-en-Y (R-Y) reconstruction in laparoscopy-assisted distal gastrectomy (LADG). One hundred twenty patients with pathological stage I gastric cancer underwent R-Y reconstruction after LADG with D1 + β lymphadenectomy between January 2004 and March 2009 and were followed up for 5 years. The patients were divided into 2 groups: the preservation group (P-CB) and the resection group (R-CB). Evaluated variables included symptoms, endoscopic findings, nutritional status, and gallstone formation at 5 years after gastrectomy. Gallstone formation was significantly less common in P-CB than in R-CB (16 vs. 33%, p = 0.035). One patient (2%) in P-CB and 4 (7%) in R-CB underwent surgery for symptomatic gallstones. On multivariate analysis of gallstone formation, R-CB was an independent risk factor for gallstone formation (odds ratio = 2.5, 95% confidential interval: 1.0-6.1, p = 0.049). Symptoms and endoscopic findings did not differ significantly between the groups. Relative values of body weight, serum albumin level, and total cholesterol level also did not significantly differ between the groups. Preserving the CB independently contributes to the prevention of gallstone formation during long-term follow-up after R-Y reconstruction following LADG.


Interrelation of Diet, Gut Microbiome, and Autoantibody Production.
B cells possess a predominant role in adaptive immune responses via antibody-dependent and -independent functions. The microbiome of the gastrointestinal tract is currently being intensively investigated due to its profound impact on various immune responses, including B cell maturation, activation, and IgA antibody responses. Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. "Western" dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies. This could contribute to multiple pathologies including autoimmune and inflammatory diseases. Here, we summarize current knowledge on the influence of various dietary components on B cell function and (auto)antibody production in relation to the gut microbiota, with a particular focus on the gut-brain axis in the pathogenesis of multiple sclerosis.


Psycho-social problems of diabetic children and adolescents.
The experience gained in the treatment of 700 diabetic children and adolescents over 20 years at the Beilinson Medical Center, Israel, is reviewed in the light of prevailing concepts. To deal with the psycho-social problems arising in this chronic disease with acute episodes, a multidisciplinary team approach has been used since 1966. The program of this team and the results obtained in relation to the control of the diabetes and to the habilitation and rehabilitation of patients within the family, at school and in adulthood (work and marriage) are described.


The dilemma of the duplicated cystic duct: a case report.
We present a rare case of a duplicated cystic duct encountered during an elective laparoscopic cholecystectomy in a patient with biliary colic. Prompt recognition of an intraoperative bile leak followed by thorough examination and recognition of the source allowed for timely and appropriate management of the affected patient with a satisfactory post-operative outcome. Our case is unique by the lack of availability of intraoperative cholangiogram at the time of surgery, which posed a significant diagnostic and therapeutic challenge, and by how aberrant anatomy was confirmed intraoperatively by reviewing prior cardiac magnetic resonance imaging. Unremarkable preoperative imaging does not rule out the presence of abnormal anatomy. Early involvement of a specialist hepatobiliary surgeon is essential in an unexplained bile leak, with a low threshold in converting to an open procedure if there is difficulty in clearly deciphering anatomy.


Screening anti-fatigue components of American ginseng saponin by analyzing spectrum-effect relationship coupled with UPLC-Q-TOF-MS.
American ginseng has an obvious anti-fatigue effect, but the effective material basis is still unclear. The spectrum-effect relationship is a scientific method that studies the correlations between chemical spectra and pharmacological effect. To reveal the real bioactive compounds in American ginseng saponin (AGS) based on a study of the underlying correlations between these compounds' occurrence in rat serum after their intake of AGS and the anti-fatigue effect of AGS. We utilized ultra-performance liquid chromatography (UPLC) with quadrupole and time-of-flight mass spectrometry (Q-TOF-MS) to analyze the extract of AGS and its constituents in serum after oral administration in rats. The anti-fatigue effect of AGS in rats was measured using the time weight-bearing swimming technique, the content of blood urea nitrogen, hepatic glycogen, and blood lactic acid. The relationship between the peak area values in fingerprints from rat serum and pharmacodynamic parameters of AGS was established using correlation analysis with partial least square regression (PLSR) method and gray correlation method. We detected and identified 22 compounds from extract, and 8 prototype components from serum. Through PLSR and gray correlation method, it was found that the ginsenosides Re, Rb1, and Rb2 were significantly positively related to the pharmacodynamic data. Based on the spectrum-effect relationship, PLSR and gray correlation method can be used to screen for the anti-fatigue components available in AGS. Such an approach is of practical significance as it provides an effective means for exploring the material basis for the efficacy of American ginseng, particularly as an anti-fatigue agent.


Bilateral endophthalmitis and symmetrical peripheral gangrene in a patient with chronic kidney disease on maintenance hemodialysis.
Dialysis patients have greater number of complications due to multiple comor-bidity and access-related infections as well as nosocomial infections due to reduced immunity and more frequent hospitalizations. Endogenous endophthalmitis is a potentially blinding ocular infection occurring in chronically debilitated patients and the use of invasive procedures. Symmetric peripheral gangrene (SPG) is defined as symmetrical distal ischemic damage in two or more sites in the absence of a major vascular occlusive disease. It carries a high mortality rate with a very high frequency of multiple limb amputations in the survivors. However, only a few case reports have described endogenous endophthalmitis in dialysis patients. Concomitant endophthalmitis and disseminated intravascular coagulation (DIC), presenting as SPG, is extremely rare and no such case was found in the literature survey. Herein, we report a very rare association of bilateral endophthalmitis with DIC and SPG in a patient with chronic kidney disease on maintenance hemodialysis.


P2X7 receptor antagonism modulates IL-1β and MMP9 in human atherosclerotic vessels.
In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs. non-atherosclerotic internal mammary artery (IMA) by using molecular biology, immune-biochemical and microscopy methodologies. We highlighted atherosclerosis-related differences between PLs and IMAs molecular patterns, and their responsivity to P2X7 antagonism. High IL-1β tissue content was associated with PLs morphology and instability/vulnerability. We demonstrated that A740003, but not KN62, decreased IL-1β and MMP9 independently from NLR family pyrin domain containing 3, but in relationship with patient's smoking status. Acting downstream P2X7 by MMPs inhibitors, diminished IL-1β mRNA without transcriptional effect at MMP9, possibly because the assumption of statin by patients. These data firstly demonstrated A740003 suitability as a specific tool to decrease inflammatory status in human vessels and might support the design of studies applying P2X7 antagonists for the local targeting and tailored therapy of atherosclerosis.


Ogataea haglerorum sp. nov., a novel member of the species complex, Ogataea (Hansenula) polymorpha.
Three strains representing a novel species of the Ogataea clade were isolated by W. T. Starmer and H. J. Phaff from rotting tissue of Opuntia phaeacantha in Arizona, USA. Analyses of the sequences of the D1/D2 LSU rRNA gene, ITS1-5.8S-ITS2, and translation elongation factor-1α (EF-1 α) showed that this novel species belongs to the Ogataea polymorpha complex formed by Ogataea angusta, Ogataea parapolymorpha and Ogataea polymorpha. The novel species differs from these species by 4-5 nucleotide substitutions in the D1/D2 domain, by 28-29 nucleotide substitutions in the EF-α gene and by 18-24 nucleotide substitutions and 2-5 indels in the ITS-5.8S region. The name Ogataea haglerorum sp. nov. is proposed for this novel species. The type strain is VKPM Y-2583T (=CBS 14645T=UCDFST 17-101T). The Mycobank number is MB 819772.


Perforated vs. nonperforated acute appendicitis: evaluation of short-term surgical outcomes in an elderly population.
Acute appendicitis is a common acute surgical abdominal condition and despite the majority of cases are observed in children and young adults, its occurrence in the elderly seems to be increasing, with a higher risk of perforation. The aim of this study was to evaluate the surgical outcomes following appendectomy for acute appendicitis in the elderly, making a comparison between perforated and nonperforated groups regarding operative time, hospital stay and postoperative complications. The medical records of 48 patients over the age of 60 years who had a pathologically confirmed diagnosis of acute appendicitis from January 2011 to December 2016 were retrospectively reviewed. Patients were grouped into those with perforated and those with non-perforated appendicitis (NPA) and a comparison was made between both groups regarding demography, operative time, length of hospital stay and postoperative complications. From 48 patients over 60 years diagnosed with acute appendicitis, a PA was removed from 10 patients (20.8%). The PA group consisted of 3 males and 7 females, and their mean age was 71.6 years (range 65-84). The NPA group included 22 males and 16 females, and their mean age was 76.5 years (range 63-96). The mean operative time was 58±18.7 minutes and 43.3±9.9 minutes in the perforated and nonperforated groups respectively, with statistically significant difference (P=0.0013). The mean length of hospital stay was similar in the PA group and in the NPA group, being 6.5±1.8 days and 5.4±1.8 days respectively, but these differences were not statistically significant (P=0.093). The frequency of postoperative complications was similar in both groups as they were observed in 3 patients (30%) of the PA group and 10 patients (26%) of the NPA group (P=0.2488). No postoperative intraabdominal abscess was observed in both groups and there was no death after the surgery. PA, despite requiring a longer mean operative time, in our series is not producing a longer hospital stay or more postoperative complications compared to NPA. The non-operative management of uncomplicated appendicitis is a reasonable option in frail patients in order to avoid the burden of morbidity related to operation, nevertheless surgery remains the standard of care in all age groups.


Vascular supply of nerves in the tarsal tunnel.
The normal vascular supply of nerves in the tarsal tunnel was studied by intra-arterial injection of latex. In general, the blood supply to the tibial nerve and its branches came directly from corresponding arteries. Each nutrient artery to the tibial nerve bifurcated on the surface of the lateral plantar nerve fasciculus to create longitudinal vessels that made anastomoses with bifurcating nutrient vessels proximally and distally. This primary longitudinal system supplied intersubfascicular vessels to the medial plantar fasciculus. The last nutrient artery from the posterior tibial artery usually supplied the terminal branching point of the tibial nerve midway through the tarsal tunnel. The lateral and medial plantar nerves received most of the nutrient vessels from their corresponding arteries in shorter intervals. In 65% of cases, the lateral plantar nerve received a nutrient vessel from the medial plantar artery. Potential anatomical areas of vascular compromise in the etiology or surgical release of tarsal tunnel syndrome are discussed.


Prostatic stromal hyperplasia with bizarre nuclei.
Prostatic stromal hyperplasia with bizarre nuclei is an uncommon variant of nodular hyperplasia that may be confused with mesenchymal malignancy but that can usually be distinguished by the degenerative character of the nuclear changes, absent to negligible mitotic rate, and relatively sparse cellularity. We report a case in a 73-year-old man and review six other cases, which, to our knowledge, are the only ones that have been reported previously.


The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation.
Freezing of gait (FOG) is a devastating motor symptom of Parkinson's disease that leads to falls, reduced mobility, and decreased quality of life. Reliably eliciting FOG has been difficult in the clinical setting, which has limited discovery of pathophysiology and/or documentation of the efficacy of treatments, such as different frequencies of subthalamic deep brain stimulation (STN DBS). In this study we validated an instrumented gait task, the turning and barrier course (TBC), with the international standard FOG questionnaire question 3 (FOG-Q3, r = 0.74, p < 0.001). The TBC is easily assembled and mimics real-life environments that elicit FOG. People with Parkinson's disease who experience FOG (freezers) spent more time freezing during the TBC compared to during forward walking (p = 0.007). Freezers also exhibited greater arrhythmicity during non-freezing gait when performing the TBC compared to forward walking (p = 0.006); this difference in gait arrhythmicity between tasks was not detected in non-freezers or controls. Freezers' non-freezing gait was more arrhythmic than that of non-freezers or controls during all walking tasks (p < 0.05). A logistic regression model determined that a combination of gait arrhythmicity, stride time, shank angular range, and asymmetry had the greatest probability of classifying a step as FOG (area under receiver operating characteristic curve = 0.754). Freezers' percent time freezing and non-freezing gait arrhythmicity decreased, and their shank angular velocity increased in the TBC during both 60 Hz and 140 Hz STN DBS (p < 0.05) to non-freezer values. The TBC is a standardized tool for eliciting FOG and demonstrating the efficacy of 60 Hz and 140 Hz STN DBS for gait impairment and FOG. The TBC revealed gait parameters that differentiated freezers from non-freezers and best predicted FOG; these may serve as relevant control variables for closed loop neurostimulation for FOG in Parkinson's disease.


Cardiovascular events after liver transplantation: MACE hurts.
The curative therapy for patients with end-stage liver disease is liver transplantation. However, liver transplantation challenges the cardiovascular system, and is associated with major adverse cardiovascular events (MACE). Immediately after implantation of the liver graft, changes in cardiac preload and afterload increase the cardiac workload. Longer-term postoperatively, a more sedentary lifestyle and enhanced appetite increase obesity and body mass index. Immunosuppressants may also affect the cardiovascular system. All these factors that liver recipients encounter impact the function of the cardiovascular system. Cardiac events are the third-leading cause of death in liver recipients. This review describes the pertinent factors that predispose to development of MACE after liver transplantation, and how to predict these cardiovascular events in the post-transplant period. We review the roles of metabolic syndrome, renal dysfunction, non-alcoholic fatty liver disease, diagnostic tests such as imaging and biomarkers, and parameters such as systolic and diastolic dysfunction, and QT interval prolongation in cardiovascular events. We summarize the current literature on scoring systems to predict cardiovascular events.


PubstractHelper: A Web-based Text-Mining Tool for Marking Sentences in Abstracts from PubMed Using Multiple User-Defined Keywords.
While a huge amount of information about biological literature can be obtained by searching the PubMed database, reading through all the titles and abstracts resulting from such a search for useful information is inefficient. Text mining makes it possible to increase this efficiency. Some websites use text mining to gather information from the PubMed database; however, they are database-oriented, using pre-defined search keywords while lacking a query interface for user-defined search inputs. We present the PubMed Abstract Reading Helper (PubstractHelper) website which combines text mining and reading assistance for an efficient PubMed search. PubstractHelper can accept a maximum of ten groups of keywords, within each group containing up to ten keywords. The principle behind the text-mining function of PubstractHelper is that keywords contained in the same sentence are likely to be related. PubstractHelper highlights sentences with co-occurring keywords in different colors. The user can download the PMID and the abstracts with color markings to be reviewed later. The PubstractHelper website can help users to identify relevant publications based on the presence of related keywords, which should be a handy tool for their research. http://bio.yungyun.com.tw/ATM/PubstractHelper.aspx and http://holab.med.ncku.edu.tw/ATM/PubstractHelper.aspx.


[Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base area with F-18-fluoro-deoxyglucose positron emission tomography].
To investigate the diagnostic value of F-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) for the recurrent or residual nasopharyngeal carcinomas in the skull base area. Nine post-irradiation nasopharyngeal carcinoma patients did FDG-PET scanning, CT/MRI imaging and underwent nasopharynx and skull base-biopsy under endoscopy. The results of FDG-PET were evaluated and compared with CT/MRI studies and biopsies. In 9 cases of post-irradiation nasopharyngeal carcinoma, CT/MRI detected 7 recurrent cases and 2 suspected recurrent cases in occipital bone and clivus. All 9 cases had accumulated FDG in nasopharynx and cranial base. A definite diagnosis was made by biopsy, 3 cases were confirmed recurrence, and others 6 cases were proved mucous chronic inflammation and (or) osteoradionecrosis. The accuracy of FDG-PET was 33.3% (3/9), and the false positive rate was 66.7% (6/9). Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base area with FDG-PET had high false-positive rate, final diagnosis must depend on histopathologic examination under endoscopy.


Sparsity-driven adaptive enhancement of underwater acoustic tonals for passive sonars.
Acoustic tonals, radiated by underwater and surface vehicles, are an important feature for passive sonar detection. An adaptive line enhancer (ALE) is usually employed in passive sonar systems as a preprocessing step to enhance the acoustic tonals from these vehicles. Unfortunately, the performance of the conventional ALE is limited by the high steady-state misadjustment, which is caused by the weight noise in the adaptation process. This paper makes use of the frequency-domain sparsity of these tonals to develop better ALEs for passive sonars. The adaptation of the proposed ALE is performed in the frequency domain. Three typical sparse penalties, l1-norm, log-sum, and l0-pseudo-norm, are incorporated into the cost function of the frequency-domain adaptation, which yield three sparsity-driven ALEs: zero-attracting (ZA), reweighted zero-attracting (RZA), and l0. The simulation shows that the signal-to-noise ratio gains of the ZA-ALE, RZA-ALE, and l0-ALE are 5.9, 8.7, and 9.7 dB, higher than that of the conventional ALE, respectively. The results of processing the real data also validate that all the sparsity-driven ALEs outperform the conventional ALE, and the l0-ALE performs the best. The proposed sparsity-driven l0-ALE is thus a promising candidate for passive sonars to enhance the tonals.


Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome.
R-loops are stable RNA-DNA hybrids that have been implicated in transcription initiation and termination, as well as in telomere maintenance, chromatin formation, and genome replication and instability. RNA Polymerase (Pol) II transcription in the protozoan parasite Trypanosoma brucei is highly unusual: virtually all genes are co-transcribed from multigene transcription units, with mRNAs generated by linked trans-splicing and polyadenylation, and transcription initiation sites display no conserved promoter motifs. Here, we describe the genome-wide distribution of R-loops in wild type mammal-infective T. brucei and in mutants lacking RNase H1, revealing both conserved and diverged functions. Conserved localization was found at centromeres, rRNA genes and retrotransposon-associated genes. RNA Pol II transcription initiation sites also displayed R-loops, suggesting a broadly conserved role despite the lack of promoter conservation or transcription initiation regulation. However, the most abundant sites of R-loop enrichment were within the regions between coding sequences of the multigene transcription units, where the hybrids coincide with sites of polyadenylation and nucleosome-depletion. Thus, instead of functioning in transcription termination the most widespread localization of R-loops in T. brucei suggests a novel correlation with pre-mRNA processing. Finally, we find little evidence for correlation between R-loop localization and mapped sites of DNA replication initiation.


Evaluation of maslinic acid with whole-body vibration training in elderly women with knee osteoarthritis.
Maslinic acid (MA) is a component derived from a natural olive-based extract known to have pharmacological functions that include suppressing inflammation. This study examined how MA, in conjunction with whole-body vibration training (WBVT), can improve knee and muscle function in elderly women with knee osteoarthritis (OA). The study was a double-blinded, placebo-controlled, randomized intervention study that enrolled individuals with knee pain. Participants were 26 females aged 65-85 years with knee OA. They performed WBVT and ingested either 16.7 mg of MA or a placebo daily for 20 weeks. We compared the effect of WBVT with placebo (WBVT/P) and WBVT with MA (WBVT/MA) in participants with various degrees of knee OA (Kellgren and Lawrence (K-L) grade) using the Japanese Orthopaedic Association (JOA) score and isokinetic dynamometer measurements to evaluate knee and muscle function with two-way ANOVA. Based on the results of two-way ANOVA analysis of muscle function measurements, there was significant interaction (time × group) (P = 0.03) in the "isokinetic extension peak torque" domain for severe OA (K-L grade ≥ 3). The simple main effect of time in the WBVT/MA group (P = 0.04) contributed to this interaction. The JOA score for WBVT/MA supported the main effect of group as having a significant correlation in the "pain on walking" (P = 0.04) and "range of motion" (P < 0.01) domains. Participants with severe knee OA in the WBVT/MA group improved in these domains, whereas the WBVT/P group had few positive results. Participants with severe OA who ingested MA in conjunction with WBVT improved their knee and muscle function. This study suggests that ingesting the anti-inflammatory supplement MA while participating in WBVT, elderly women can reduce knee OA and improve their knee muscle strength.


[Gene transfers of kallikrein, bradykinin receptor B2 and a mutated B2 receptor stimulate neoangiogenesis in peripheral ischemia].
In this work, we evaluated the angiogenic effect of the gene transfer of human tissue kallikrein (TK), bradykinin B2 receptor (B2R) and a mutated form (RB2m) in a rabbit peripheral model of ischaemia. We studied the effects of the transfection of each of these factors and the effects of their co-transfection. In New Zealand anesthetised rabbits we first induced an ischaemia of the left posterior leg by ligation-excision of the superficial femoral artery and its collaterals. Seven days later, we performed i.m. injections in the ischemic tight with transfection solutions containing either the control (pcDNA3 empty backbone) or the pcDNA3-TK, the pcDNA3-TK and the pcDNA3-B2R, the pcDNA3-TK and the pcDNA3-B2Rm. Twenty eight days later, the therapeutic effect was evaluated using ultrasonographic debitmetry of the common iliac artery, perfusion index (PI) = ischemic leg blood flow /non ischemic leg blood flow (%) and capillaries measurements i.e. capillary density: number of vessels/mm2 and the ratio of vessels/muscular fiber, in the adductors and gastrocnemian muscles. The PI was increased in each treated group vs control (32.61 +/- 5.2%), pcDNA3-TK: 59.72 +/- 2.33%; p = 0.001; pcDNA3-RB2: 55.25 +/- 2.29%; p = 0.008; pcDNA3-TK + pcDNA3-RB2: 84.77 +/- 3.15%; p < 0.001; pcDNA3-TK + pcDNA3-RB2m: 103.25 +/- 4.9%; p < 0.001. The capillary density and the vessel/muscular fiber ratio increased in a parallel with the hemodynamic in the ischemic adductors (pcDNA3-TK + pcDNA3-B2Rm > pcDNA3-TK + pcDNA3-RB2 > pcDNA3-TK = pcDNA3-B2R; p < 0.001). There was no angiogenic effect measurable neither in the non ischemic adductors (right) nor in the gastrocnemian muscles. In rabbit peripheral ischaemia, the cotransfection of TK and B2R increases the arterial flow in the treated leg and potentiates the neoangiogenesis. Cotransfection of the B2Rm cDNA enhanced the synergic effect of this therapeutic strategy.


Manipulating the orientation of an organic adsorbate on silicon: a NEXAFS study of acetophenone on Si(0 0 1).
We investigate the chemical and structural configuration of acetophenone on Si(0 0 1) using synchrotron radiation core-level spectroscopy techniques and density functional theory calculations. Samples were prepared by vapour phase dosing of clean Si(0 0 1) surfaces with acetophenone in ultrahigh vacuum. Near edge x-ray absorption fine structure spectroscopy and photoelectron spectroscopy measurements were made at room temperature as a function of coverage density and post-deposition anneal temperature. We show that the dominant room temperature adsorption structure lies flat on the substrate, while moderate thermal annealing induces the breaking of Si-C bonds between the phenyl ring and the surface resulting in the reorientation of the adsorbate into an upright configuration.


Searching for stereoisomerism in crystallographic databases: algorithm, analysis and chiral curiosities.
The automated identification of chiral centres in molecular residues is a non-trivial task. Current tools that allow the user to analyze crystallographic data entries do not identify chiral centres in some of the more complex ring structures, or lack the possibility to determine and compare the chirality of multiple structures. This article presents an approach to identify asymmetric C atoms, which is based on the atomic walk count algorithm presented by Rücker & Rücker [(1993), J. Chem. Inf. Comput. Sci. 33, 683-695]. The algorithm, which we implemented in a computer program named ChiChi, is able to compare isomeric residues based on the chiral centres that were identified. This allows for discrimination between enantiomers, diastereomers and constitutional isomers that are present in crystallographic databases. ChiChi was used to process 254 354 organic entries from the Cambridge Structural Database (CSD). A thorough analysis of stereoisomerism in the CSD is presented accompanied by a collection of chiral curiosities that illustrate the strength and versatility of this approach.


Integrating regression formulas and kernel functions into locally adaptive knowledge-based neural networks: a case study on renal function evaluation.
In many medical areas, there exist different regression formulas to predict/evaluate a medical outcome on the same problem, each of them being efficient only in a particular sub-space of the problem space. The paper aims at the development of a generic, incremental learning model that includes all available regression formulas for a particular prediction problem to define local areas of the problem space with their best performing formula along with useful explanation rules. Another objective of the paper is to develop a specific model for renal function evaluation using nine existing formulas. We have used a connectionist neuro-fuzzy approach and have developed a knowledge-based neural network model (KBNN) which incorporates and adapts incrementally several existing regression formulas and kernel functions. The model incorporates different non-linear regression functions as neurons in its hidden layer and adapts these functions through incremental learning from data in particular local areas of the space. More specifically, each hidden neural node has a pair of functions associated with it--one regression formula, that represents existing knowledge and one Gaussian kernel function, that defines the sub-space of the whole problem space, in which the formula is locally adapted to new data. All these functions are aggregated and changed through incremental learning. The proposed KBNN model is illustrated using a medical dataset of observed patient glomerular filtration rate (GFR) measurements for renal function evaluation. In this case study, the regression function for each cluster is selected by the model from nine formulas commonly used by medical practitioners to predict GFR. 441 GFR data vectors from 141 patients taken from 12 sites in Australia and New Zealand have been used as a case study experimental data set. The proposed GFR prediction model, based on the proposed generic KBNN model, outperforms at least by 10% accuracy any of the individual regression formulas or a standard neural network model. Furthermore, we have derived locally adapted regression formulas to perform best on local clusters of data along with useful explanatory rules. The proposed KBNN model manifests better accuracy then existing regression formulas or neural network models for renal function evaluation and extracts modified formulas that perform well in local areas of the problem space.


Evaluation of Commercial 6-Phytases on Growth Performance, Bone Mineral Content, and Feed Digestibility of Broiler Chicks.
We evaluated the effects of 6-phytases on the growth performance of broilers (UK Chunky) under the recommended supplier-application dosage of each phytase. A nutritionally sufficient standard diet was administered as the base diets in the positive control feed. The diet in the negative control feed was designed by reducing total phosphorous, non-phytate phosphorus, and calcium by 0.1% to evaluate the effect of the nutrient restriction on broilers. Four 6-phytases were added to negative control feeds at the level of the recommended dosage of each product to compare the effect of phytases on broiler technical performance, tibia ash, and feed digestibility. Nine hundred one-day-old broiler chicks (males and females) were distributed in a completely randomized design composed of six treatments and three replicates of 50 chicks each. Chicks were fed ad libitum for 49 days. Body weight gain and feed intake were recorded on days 21 and 49, tibia ash was measured on day 21, and apparent ileal digestibility of dry matter, crude protein, and total phosphorus were analyzed on day 49. Birds reared with test feeds supplemented with phytase showed higher body weight gain and feed intake compared to those of the negative control birds. No significant differences in traits were observed among different phytase treatments. Similarly, the percentage of tibia ash increased when phytase was supplemented, resulting in higher bone levels compared to that of the positive control. The apparent ileal digestibility of crude protein and total phosphorus was enhanced by supplementing negative control diets with phytases.


Efficacy of oil and gas produced water as a dust suppressant.
The effectiveness of oil and gas produced water (OGPW) applied to unpaved roads to reduce particulate matter (PM10) generation has not been well-characterized. Here we quantify the efficacy of OGPW compared to commercial and alternative byproducts as dust suppressants applied to unpaved roads and estimate efficacy of a dust suppressant extrapolated from both lab experiments and published data for OGPW across U.S. states. Both treated and untreated OGPW, simulated brines, and commercial dust suppressants were characterized by major and trace element composition and then applied to road aggregate in the laboratory. PM10 generation after treatment was quantified, both before and after simulated rain events to assess the need for multiple applications. We found the dust suppression efficacy of all OGPW to be less than commercial products and alternative byproducts such as waste soybean oil. In addition, OGPW lost efficacy following simulated rain events, which would require repeated applications of OGPW to maintain dust suppression. The dust suppression efficacy of OGPW can be estimated based on two chemical measurements, the sodium absorption ratio (SAR) and the total dissolved solids (TDS). OGPW with the lowest SAR and highest TDS performed best as dust suppressants while high SAR and lower TDS led to greater dust generation.


The Syrian hamster pineal gland responds to isoproterenol in vivo at night.
Failure of isoproterenol (ISO) injections to raise pineal melatonin content has generated doubt about beta-adrenergic control of the melatonin rhythm in Syrian hamsters. However, the effect of ISO injected at night after light-induced reduction of pineal melatonin has not been reported. In this study, light exposure began at 6 1/4 h into one (normally 10-h) dark phase. The hamsters were injected with either ISO (1 mg/kg) or vehicle 15 min later when pineal melatonin content was low. Light exposure continued. Two h after ISO but not vehicle injection, pineal melatonin content rose more than six-fold. In other animals injected at the end of the usual light phase then kept in light for 2 h, pineal melatonin was equally low after ISO or vehicle injection. The Syrian hamster pineal gland can respond in vivo to a beta-adrenergic agonist injected at the physiologically relevant time of the normal nocturnal melatonin surge. This finding, taken together with the previously reported inhibition of the endogenous nocturnal melatonin surge with a beta-blocking drug, suggests that a beta-adrenergic mechanism controls the hamster pineal melatonin rhythm.


Excited-State Gradients in Polarizable QM/MM Models: An Induced Dipole Formulation.
Charge and structural relaxation of electronically excited states in embedded systems are strongly affected by the environment. It is known that the largest part of environment effects comes from electrostatics. However, polarization can also play a role by tuning the electronic and geometrical properties of the states, finally modifying the fluorescence. Here we present the formulation of analytical excited-state gradients within a polarizable QM/MM approach and their implementation within the ONIOM framework. A time-dependent DFT level of theory is used in combination with an induced dipole formulation of the polarizable embedding. The formation and relaxation of the bright excited state of an organic dye (DAPI) intercalated in a DNA pocket is used to quantify the role played by the mutual polarization between the QM subsystem and the embedding and also to investigate the onset of overpolarization, which is a known limit of the model with potentially detrimental effects. On the one hand, the results indicate the robustness of the QM-classical interface and, on the other hand, show the non-negligible effect of polarization between DAPI and a DNA pocket in determining the fluorescence properties of the embedded dye.


Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women.
Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: [Formula: see text]] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women's Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07-1.31, P for trend <0.01) and OR = 1.76 (95% CI 1.33-2.33, P for trend <0.01) comparing extreme quartiles and adjusting for potential confounders. These associations still persisted after adjusting for the polyunsaturated to saturated fat ratio. Our study indicated that higher LI based on either dietary or plasma measurements, representing higher FA lipophilicity, was associated with elevated risk of CHD among postmenopausal women.


Bend and splay elastic constants at a reentrant isotropic-calamitic-nematic phase transition.
By measuring the ratio between the major and minor axes of closed elliptical loops created by a magnetic field, the ratio between the bend (K33) and splay (K11) elastic constants of a lyotropic mixture of potassium laurate, decanol, and water in the calamitic nematic phase is measured as a function of temperature. Since these systems present two nematic-isotropic phase transitions--the usual one, at high temperatures, and a reentrant one, at low temperatures--such measurements are used to compare the behavior of these elastic constants at the neighborhoods of these two distinct regions, which have in common the vanishing of the order parameter. The experimental data have revealed the existence of two elastic constant branches, characterizing a distinct low- and high-temperature behavior. To explain such asymmetry we support that, because of the lyotropic nature of the compound, the micellar variation, which is mainly responsible for the reentrant phase, plays a distinct role at these two phase transitions.


Chemically driven hydrodynamic instabilities.
In the gravity field, density changes triggered by a kinetic scheme as simple as A+B-->C can induce or affect buoyancy-driven instabilities at a horizontal interface between two solutions containing initially the scalars A and B. On the basis of a general reaction-diffusion-convection model, we analyze to what extent the reaction can destabilize otherwise buoyantly stable density stratifications. We furthermore show that, even if the underlying nonreactive system is buoyantly unstable, the reaction breaks the symmetry of the developing patterns. This is demonstrated both numerically and experimentally on the specific example of a simple acid-base neutralization reaction.


Minor-groove recognition of the self-complementary duplex d(CGCGAATTCGCG)2 by Hoechst 33258: a high-field NMR study.
The interaction of Hoechst 33258, a fluorescent DNA stain, has been studied by using the synthetic, self-complementary oligonucleotide duplex d(CGCGAATTCGCG)2. Spectrofluorometric Scatchard analysis indicated that there was only a single class of binding site and that the 1:1 complex had a dissociation constant of (3.47 +/- 0.1) X 10(-6) M at 25 degrees C. Spectroscopic titration by high-field 1H NMR confirmed the 1:1 complex and by means of ID and 2D (NOESY, COSY) techniques the binding site was defined as the minor groove formed by the AATT stretch. Plentiful cross-peaks were measurable and resonance doubling occurred because of the lifting of the diad symmetry of the oligonucleotide on ligand binding. Many individual resonances of both strands of the DNA could be assigned for the complex because of these features, along with the occurrence of slow exchange on the NMR time scale. The results of this NMR spectroscopic solution study were compared with those of previous X-ray crystallographic studies of the same complex. From nuclear Overhauser effect data measured for the complex, a detailed three-dimensional model was constructed with the aid of molecular graphics.


Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study.
We aimed to investigate differences in upper and lower respiratory tract symptoms in relation to respiratory viral infections detected with polymerase chain reaction assays in young children with cystic fibrosis and healthy control subjects. In a 6-month winter period, 20 young children with cystic fibrosis and 18 age-matched, healthy, control subjects were contacted twice per week for detection of symptoms of an acute respiratory illness. If any symptom was present, then a home visit was made for physical examination and collection of nasopharyngeal swabs for viral analysis. In addition, parents were instructed to collect nasopharyngeal swabs every 2 weeks. Children with cystic fibrosis and healthy control subjects had similar frequencies of acute respiratory illnesses (3.8+/-1.0 and 4.2+/-1.7 episodes, respectively). Although there were no significant differences in upper respiratory tract symptoms, the children with cystic fibrosis had longer periods of lower respiratory tract symptoms (22.4+/-22.2 vs 12.8+/-13.8 days) and a higher mean severity score per episode (2.35+/-0.64 vs 1.92+/-0.46). In addition, similar increases in upper respiratory tract symptom scores were associated with significantly greater increases in lower respiratory tract symptom scores in children with cystic fibrosis. No differences in the seasonal occurrences and distributions of respiratory viruses were observed, with picornaviruses and coronaviruses being the most prevalent. Although there were no differences in the seasonal occurrences and distributions of polymerase chain reaction-detected respiratory viruses, acute respiratory illnesses were frequently associated with increased lower respiratory tract morbidity in young children with cystic fibrosis.


Impact of musculoskeletal disorders on quality of life of patients visiting tertiary care hospital.
To determine the impact of musculoskeletal disorders on patients' quality of life. The cross-sectional study was conducted at the Khyber Teaching Hospital, Peshawar, Pakistan, from September 2018 to March 2019, and comprised patients of either gender having a variety of musculoskeletal disorders. Data was collected using a validated EuroQol-5-Dimension-3-Level scale. Data was analysed using SPSS 20. Of the 377 participants, 204(54.1%) were males, and 173(45.9%) were females. The overall mean age was 35.9±12.5 years. Muscular weakness was the most commonly encountered problem 153(40.6%), followed by muscle stiffness 49(13.0%) and adhesive capsulitis 39(10.3%). Patients with musculoskeletal disorders had moderately good 'health state today' score of 56.03±20.175 on VAS. Musculoskeletal disorders were found to have a negative impact on quality of life and health status of the patients.


Facial lymph nodes: normal and abnormal CT appearance.
Facial lymph node involvement by neoplastic disease is an unusual occurrence. The purpose of this study was to determine the normal and abnormal radiologic appearance of the facial nodes. Two hundred enhanced computed tomographic (CT) studies of patients not at risk for facial node metastasis were studied prospectively to establish a normal control group. One hundred consecutive patients with extensive recurrent or primary cancer of the epidermal structures of the face, the sinonasal region or deep face, or the mucosal surface of the oral cavity were examined prospectively to establish a prevalence for metastatic facial adenopathy. In addition, all cases of facial node metastases seen on imaging studies over an 11-year period (n = 21) were examined retrospectively to establish the spectrum of facial lymphadenopathy. Normal nodes could not be confidently identified on CT studies. When nodal metastasis occurred, it was often in the setting of recurrent disease. The infraorbital nodes tended to be the site of origin for lymphomas isolated to the canine fossa.


Coronary Access and Percutaneous Coronary Intervention Up to 3 Years After Transcatheter Aortic Valve Implantation With a Balloon-Expandable Valve.
Coronary artery disease and aortic stenosis often coexist. Transcatheter aortic valve implantation (TAVI) has emerged as a valid therapeutic option for younger, lower-risk patients who may eventually require coronary artery disease treatment. Thus, post-TAVI coronary access (CA) and percutaneous coronary intervention are expected to increase. The purpose of this study was to retrospectively evaluate patients who were enrolled in the SOURCE 3 (SAPIEN 3 Aortic Bioprosthesis European Outcome) European registry for treatment with the balloon-expandable SAPIEN 3 transcatheter heart valve and underwent CA with or without percutaneous coronary intervention after TAVI. Baseline characteristics and clinical outcomes of patients with or without CA up to 3 years after TAVI were compared. A Kaplan-Meier estimate with a univariate model determined the impact of CA on cardiac mortality. Of 1936 TAVI patients (mean age 81.6 years, 52% male), 68 (3.5%) had CA within 3 years (mean 441±332 days) after TAVI. At baseline, the logistic EuroSCORE was similar (20.2% versus 18.3%, P=0.2, CA and non-CA groups, respectively). Higher rates of coronary artery disease (76.5% versus 50.6%, P<0.001), myocardial infarction (20.6% versus 11.5%, P=0.03) and previous coronary artery bypass graft (22.1% versus 11.0%, P=0.01) were present in the CA group. In 100% of patients, CA was successfully achieved. The clinical success of percutaneous coronary intervention was 97.9%. Cardiovascular mortality was numerically higher in patients with CA than in those without CA. In the large SOURCE 3 European registry, CA was needed at 3-year follow-up after TAVI with a balloon-expandable valve in 3.5% of patients and was successful in all patients. The clinical success of percutaneous coronary intervention was 97.9%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02698956.


In vivo protective effect of tumour necrosis factor alpha against experimental infection with herpes simplex virus type 1.
C57BL/6 mice, which differ genetically from other strains by their resistance to herpes simplex virus type 1 (HSV-1) infection, were inoculated intraperitoneally with different doses of tumour necrosis factor alpha (TNF-alpha). Mice pretreated with 100 ng, or even 10 ng, of TNF-alpha showed prolonged survival compared to control mice that were infected with 10(7) p.f.u. of HSV-1. Significant protection was observed in mice injected 4 or 8 h prior to or after HSV-1 inoculation, respectively. Protection was also observed when mice which differed at their H-2 locus were treated with TNF-alpha after infection with HSV-1. Interferon could not be detected in the sera of mice at different time points after infection with HSV-1 or injection of TNF-alpha and there was no enhanced interferon titre in mice treated with both TNF-alpha and HSV-I, suggesting some interferon-independent protection. However, mice treated with TNF-alpha showed a marked activation of natural killer (NK) cells compared to untreated control mice or mice that were treated with HSV-1 alone. To test whether enhanced NK cell activity is responsible for TNF-alpha-induced protection, mice were injected with the NK cell-specific antibody anti-asialo Gm-1. In this experimental protocol the survival rate was almost unaffected, indicating that the observed protection was not due to activation of NK cells and that TNF-alpha is involved in the regulation of antiviral mechanisms other than the activation of interferons. Although additional production of interferon induced by TNF-alpha cannot be excluded, an antiviral effect of TNF-alpha on the course of HSV-1 infection may be postulated from our data.


Perception of workplace social-sexual behavior as sexual harassment post #MeToo in Scandinavia.
In this study we examined how people perceive social-sexual behavior of women and men, and how these perceptions were associated with beliefs about the outcomes of the #MeToo movement, sexism, traditional values, and gender equality. In addition, we examined the effect of having experienced sexual harassment on such perceptions. Analyses were performed on a Norwegian snowball social media sample covering 321 women and 168 men, aged 18-59 (M = 33.1). Outcome variables covered perceptions of scenarios that described opposite-sex social-sexual behaviors performed by female and male actors within the workplace environment. Path analysis showed that negative beliefs about the outcomes of the #MeToo movement was the principal predictor for perception of female and male social-sexual behavior as sexual harassment for women and men participants. Traditional values, gender equality, and hostile sexism toward women were all associated with perception of social-sexual behavior as sexual harassment, however the effects of these variables were only indirect and fully accounted for by the effect of negative #MeToo beliefs. For women, having experienced sexual harassment was associated with hostile sexism toward men, but had no effect on the perceptions over and above the effect of the other variables in the model. The predictors on participants' perceptions were highly similar for women and men and for evaluations of female and male actors. Theoretical and methodological implications are discussed.


Influence of Violation of Regeneration in People over 35-40 Years Old on Decrease in Production of Sexual Hormones.
With age the quantity of pluripotent stem cells gradually decreases. It leads to violation of renewal of tissues, including tissues of endocrine organs, at people over 35-40 years old. Artificial formation of the chimeral individual may be used for recovery of the pool of pluripotent stem cells in patients older than 40-50 years old. Transfusions of mononuclear fraction of peripheral blood procured from young donors 18-23 years old with the same blood groups and sex as the recipient (patent of the Russian Federation № 2350340), allows people over 40 years old to reestablish the pool of pluripotent stem cells, the process of tissue renewal and the production of sex hormones, and can also be seen as a promising way to reduce biological age, while providing a significant prolongation of life and while maintaining a high quality of life. Transfusions of mononuclear fraction of peripheral blood are required to be carried out multiple times before the restoration of the numerical strength of the recipients' pool of pluripotent stem cells is complete. The effectiveness of regeneration reconstitution in individuals older than 40 years old upon receiving transfusions of allogeneic pluripotent stem cells depends on the difference in age between the recipient and the young donor. When there is a major difference in age between young donors and recipients over 40 years old, the proliferative potential of pluripotent stem cells of donors (their ability to maintain the number of own pool) is higher than the proliferative potential of the recipient. In response to the formation of colony-stimulating growth factors, this leads to the dominance of transfused and formed colonies in the bone marrow of the donor's pluripotent stem cells over the analogous cells of recipients when renewing all of their tissues. The latter occurs mainly due to the donors' stem cells.


Joint status, pain and quality of life in elderly people with haemophilia: A case-control study.
Elderly people with haemophilia (PwH) develop haemophilic arthropathy, pain, and reduced health-related quality of life (HR-QoL). The condition of elderly mild haemophilia patients have rarely been evaluated. This study aimed to compare joint status, pain, and HR-QoL between elderly with mild, moderate/severe haemophilia and healthy elderlies. Knee/ankle abnormalities were assessed by ultrasound (HEAD-US) and physical examination (HJHS 2.1). Pain severity and pain interference were investigated using the Brief Pain Inventory. Pressure pain thresholds (PPTs) were obtained at knees/ankles and forehead. Functional limitations were evaluated using the 2-Minute-Walking-Test, Timed-Up-and-Go and HAL. The EQ-5D-5L questionnaire evaluated HR-QoL. Healthy controls (HCs) and elderly individuals with moderate/severe and mild haemophilia were compared using Kruskal-Wallis and Mann-Whitney U tests. From the 46 elderly PwH approached, 40 individuals (≥60 years) with haemophilia A/B (17 moderate/severe; 23 mild) and 20 age-matched HCs were recruited. Moderate/severe PwH displayed worse joint status, lower PPTs, and poorer HR-QoL than mild PwH and HCs (p-value = .010-<.001). HEAD-US abnormalities were observed in 100% of knees and 94% of ankles in moderate/severe PwH, versus 50% of knees and 61% of ankles in mild PwH. Pain was reported by 80% and 57% of moderate/severe and mild PwH, respectively. Low PPTs, functional limitations, and poor HR-QoL scores were likewise observed in some mild PwH, yet without significantly differing from HCs. This study highlights poor joint/functional status, pain, and HR-QoL outcomes in elderly with moderate/severe haemophilia. A few mild haemophilia subjects presented joint abnormalities, pain, functional limitations, and poor HR-QoL, without significantly differing from HCs. Elderly individuals with mild haemophilia have not yet been extensively studied, whereas moderate/severe haemophilia individuals have proven to suffer from haemophilic arthropathy, pain, and poor health-related quality of life (HR-QoL). Using a case-control design, joint status, pain, and HR-QoL outcomes were examined in elderly haemophilia individuals and compared with those of healthy controls (HCs). Elderly moderate/severe haemophilia individuals exhibited worse joint status, increased joint pain sensitivity, and reduced HR-QoL compared with both mild haemophilia subjects and HCs. A subset of mild haemophilia subjects exhibited poor joint status, pain, and HR-QoL outcomes, without any differences noted when compared with HCs.


A comparative study of microstructural development in paired human hepatic and gallbladder biles.
Cholesterol gallstones usually develop in the gallbladder and rarely form in bile ducts even in patients with highly lithogenic bile. Bile concentration and proteins (e.g. mucin) may affect crystallization, but the exact nature of this effect, especially in relation to crystallization pathways and microstructural evolution remains unclear. We examined lipid microstructures in paired hepatic and gallbladder biles to reveal ones that are essential for crystallization. Combining digital light microscopy with cryogenic-temperature transmission electron microscopy we are able to directly visualize and compare the time evolution of lipid microstructures in paired hepatic, gallbladder and diluted gallbladder biles of gallstone patients and controls, without drying or separating. Gallbladder bile exhibited several multilamellar vesicles and spheroidal micelles preceding and throughout crystallization. Vesicle morphology changed before crystallization was observed. In contrast, hepatic bile revealed almost no crystallization and while a variety of unilamellar vesicles and spheroidal micelles existed throughout the examination, multilamellar vesicles were rare. Diluted gallbladder bile was different from native gallbladder bile, as well as the paired hepatic bile, yielding occasional crystallization. Our findings suggest that maturing multilamellar vesicles precede (and at least partially initiate) crystallization in gallbladder bile. Although microstructural development seems to be concentration dependent, dilution of gallbladder bile to hepatic bile concentrations neither makes it identical to hepatic bile, nor prevents crystallization.


The implicit theories of rapists: what convicted offenders tell us.
Twenty years of research into sex offenders' cognitive distortions has primarily focused on the measurement of distortions rather than on theorizing about the underlying structures that are responsible for generating and organizing them. Recently T. Ward (2000; T. Ward & T. Keenan, 1999) suggested that offenders have underlying causal theories about themselves, their victims, and broader categories of people (e.g., women and children), and that these implicit theories enable post hoc explanation as well as prediction of people's actions and reactions. D. L. L. Polaschek and T. Ward (2002) examined rape-related attitudinal scales and constructed and outlined five core implicit theories. Here, we examined whether evidence for these five theories was also found in offense process descriptions generated from interviews with 37 imprisoned rapists. Coding of the descriptions revealed support for all five theories.


Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase.
G protein-coupled receptor (GPCR) signaling is precisely controlled to avoid overstimulation that results in detrimental consequences. Gβγ signaling is negatively regulated by a Cullin3 (Cul3)-dependent E3 ligase, KCTD5, which triggers ubiquitination and degradation of free Gβγ. Here, we report the cryo-electron microscopy structures of the KCTD5-Gβγ fusion complex and the KCTD7-Cul3 complex. KCTD5 in pentameric form engages symmetrically with five copies of Gβγ through its C-terminal domain. The unique pentameric assembly of the KCTD5/Cul3 E3 ligase places the ubiquitin-conjugating enzyme (E2) and the modification sites of Gβγ in close proximity and allows simultaneous transfer of ubiquitin from E2 to five Gβγ subunits. Moreover, we show that ubiquitination of Gβγ by KCTD5 is important for fine-tuning cyclic adenosine 3´,5´-monophosphate signaling of GPCRs. Our studies provide unprecedented insights into mechanisms of substrate recognition by unusual pentameric E3 ligases and highlight the KCTD family as emerging regulators of GPCR signaling.


Effects of a traditional Chinese medicine formula and its extraction on muscle fiber characteristics in finishing pigs, porcine cell proliferation and isoforms of myosin heavy chain gene expression in myocytes.
This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula's extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber I, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type I fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC I, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC I and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor γ coactivator-1α and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by 4 μg/mL and 20 μg/mL TCMF water extraction (p<0.05). Both 1 μg/mL and 5 μg/mL of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC I mRNA expression in porcine myocytes was decreased by 5 μg/mL TCMF water extraction (p<0.05). Porcine myocyte MyHC I and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by 5 μg/mL TCMF ethyl acetate extraction (p<0.05). MyHC I and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by 1 μg/mL TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by 5 μg/mL TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by 1 μg/mL in a TCMF petroleum ether extraction (p<0.05). These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes.


Treatment of advanced non-Hodgkin's lymphoma with vincristine infusion.
Twenty-five patients with a variety of histologic types of advanced non-Hodgkin's lymphoma refractory to previous chemotherapy were entered into a trial of vincristine infusion. Patients received 5-day courses of vincristine 0.25 mg/m2/day by continuous intravenous infusion after an initial 0.5 mg intravenous bolus injection. Courses were repeated every 3 weeks. Objective responses were observed in nine patients (36%), all of whom had previously received vincristine given by conventional bolus injection. A complete response occurred in a patient with diffuse mixed histiocytic lymphocytic lymphoma, and partial responses were observed in eight patients with the following histologic types: diffuse poorly differentiated lymphocytic (4); nodular poorly differentiated lymphocytic (2); diffuse mixed histiocytic lymphocytic (1); and diffuse histiocytic (1). Duration of response lasted from 1.2 to 16.2 months (mean, 4.4 months). The principal complication of therapy was mild-to-moderate neurotoxicity; this occurred in 12 patients (48%) who received a total of 54 courses of vincristine infusion. Hematologic toxicity was minimal and nausea/vomiting did not occur. Vincristine infusion may afford palliation for patients with advanced non-Hodgkin's lymphomas who have become refractory to standard chemotherapeutic regimens even if they have received prior vincristine by conventional bolus injection. These data suggest the possibility of enhancing the therapeutic efficacy of vincristine in the treatment of non-Hodgkin's lymphoma by use of an infusion technique.


Systemic effects of fluticasone nasal spray: report of 2 cases.
To describe two clinical cases of systemic side effects from use of fluticasone nasal spray. A retrospective review of medical records of two patients using this drug was undertaken, and their clinical presentations and laboratory data are summarized. Despite many clinical reports about the potential side effects from inhaled corticosteroids, no previously published clinical reports or studies have addressed such problems with the use of potent glucocorticoid nasal sprays. Two patients are described in whom different clinical problems developed after overuse of fluticasone nasal spray, a commonly advertised and prescribed drug. One patient was admitted to the hospital with symptoms of adrenal insufficiency. In the other patient, bone mineral density decreased substantially in 1 to 2 years despite preventive estrogen therapy. These patients had suppressed plasma or urinary cortisol, a low plasma adrenocorticotropic hormone (corticotropin) level, or an abnormal response to a cosyntropin stimulation test. Patients should be clearly warned that the prescribed dosing for fluticasone nasal spray should be carefully followed because overuse may cause serious side effects.


Eutectic melting of LiBH4-KBH4.
Eutectic melting in mixtures of alkali and alkali earth metal borohydrides can pave the way for new applications as fast ionic conductors, and facilitate hydrogen release by low temperature chemical reactions and convenient nanoconfinement. Here, we determine the eutectic composition for the lithium potassium borohydride system, 0.725LiBH4-0.275KBH4, with the lowest melting point, Tmelt ∼105 °C, of all known alkali and alkali earth metal borohydride mixtures. Mechanochemistry and manual mixing of LiBH4-KBH4 mixtures facilitate the formation of LiK(BH4)2. However, the melting or heat treatments used in this work do not produce LiK(BH4)2. The bimetallic borohydride dissociates into the monometallic borohydrides at ∼95 °C and partial melting occurs at ∼105 °C. Analysis of the unit cell volumes of LiBH4, KBH4 and LiK(BH4)2 in the temperature range 25 to 90 °C indicates that the formation of the bimetallic borohydride is facilitated by a more dense packing as compared to the reactants. Thus, LiK(BH4)2 is considered metastable and the formation is pressure induced. A phase diagram for the LiBH4-KBH4 system is established, which illustrates the low eutectic melting point and the stability range for the bimetallic borohydride, LiK(BH4)2.


Accelerating Research With Technology: Rapid Recruitment for a Large-Scale Web-Based Sleep Study.
Participant recruitment can be a significant bottleneck in carrying out research studies. Connected health and mobile health platforms allow for the development of Web-based studies that can offer improvement in this domain. Sleep is of vital importance to the mental and physical health of all individuals, yet is understudied on a large scale or beyond the focus of sleep disorders. For this reason and owing to the availability of digital sleep tracking tools, sleep is well suited to being studied in a Web-based environment. The aim of this study was to investigate a method for speeding up the recruitment process and maximizing participant engagement using a novel approach, the Achievement Studies platform (Evidation Health, Inc, San Mateo, CA, USA), while carrying out a study that examined the relationship between participant sleep and daytime function. Participants could access the Web-based study platform at any time from any computer or Web-enabled device to complete study procedures and track study progress. Achievement community members were invited to the study and assessed for eligibility. Eligible participants completed an electronic informed consent process to enroll in the study and were subsequently invited to complete an electronic baseline questionnaire. Then, they were asked to connect a wearable device account through their study dashboard, which shared their device data with the research team. The data were used to provide objective sleep and activity metrics for the study. Participants who completed the baseline questionnaires were subsequently sent a daily single-item Sleepiness Checker activity for 7 consecutive days at baseline and every 3 months thereafter for 1 year. Overall, 1156 participants enrolled in the study within a 5-day recruitment window. In the 1st hour, the enrollment rate was 6.6 participants per minute (394 per hour). In the first 24 hours, the enrollment rate was 0.8 participants per minute (47 participants per hour). Overall, 1132 participants completed the baseline questionnaires (1132/1156, 97.9%) and 1047 participants completed the initial Sleepiness Checker activity (1047/1156, 90.6%). Furthermore, 1000 participants provided activity-specific wearable data (1000/1156, 86.5%) and 982 provided sleep-specific wearable data (982/1156, 84.9%). The Achievement Studies platform allowed for rapid recruitment and high study engagement (survey completion and device data sharing). This approach to carrying out research appears promising. However, conducting research in this way requires that participants have internet access and own and use a wearable device. As such, our sample may not be representative of the general population.


Connectivity Strategies in Managing a POCT Service.
Point of Care Testing is increasingly being used for diagnosis and management of various disease states. Management of different Point of Care instruments at multiple sites can be challenging, particularly when such instruments are operated by non technical staff. Connectivity is critical for optimal management of these services which are intimately linked to operator training and competency and are important in minimising harm to the patient by reducing analytical errors. Furthermore, connectivity improves turn around time leading to faster decision making by physicians. Recent advances in technology such as 5G and artificial intelligence are likely to lead to a greater focus on personalized care as a result of big data analysis and development of algorithms.