Effects of opioid receptor ligands in rats trained to discriminate 22 from 2 hours of food deprivation suggest a lack of opioid involvement in eating for hunger.
It is well accepted that opioids promote feeding for reward. Some studies suggest a potential involvement in hunger-driven intake, but they suffer from the scarcity of methodologies differentiating between factors that intersect eating for pleasure versus energy. Here, we used a unique food deprivation discrimination paradigm to test a hypothesis that, since opioids appear to control feeding reward, injection of opioid agonists would not produce effects akin to 22 h of food deprivation. We trained rats to discriminate between 22 h and 2 h food deprivation in a two-lever, operant discrimination procedure. We tested whether opioid agonists at orexigenic doses produce discriminative stimulus effects similar to 22 h deprivation. We injected DAMGO, DSLET, or orphanin FQ in the paraventricular hypothalamic nucleus (PVN), a site regulating hunger/satiety, and butorphanol subcutaneously (to produce maximum consumption). We assessed the ability of the opioid antagonist, naltrexone, to reduce the discriminative stimulus effects of 22 h deprivation and of the 22 h deprivation-like discriminative stimulus effects of PVN-injected hunger mediator, neuropeptide Y (NPY). In contrast to PVN NPY, centrally or peripherally injected opioid agonists failed to induce discriminative stimuli similar to those of 22 h deprivation. In line with that, naltrexone did not reduce the hunger discriminative stimuli induced by either 22 h deprivation or NPY administration in 2 h food-restricted subjects, even though doses used therein were sufficient to decrease deprivation-induced feeding in a non-operant setting in animals familiar with consequences of 2 h and 22 h deprivation. We conclude that opioids promote feeding for reward rather than in order to replenish lacking energy.


Depression and 24 gastrointestinal diseases: a Mendelian randomization study.
The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.


Polyphenols as potential inhibitors of amyloid aggregation and toxicity: possible significance to Alzheimer's disease.
Beta-amyloid (Abeta)likely plays a pivotal role in the etiology of Alzheimer's disease (AD). Consequently, Abeta associated pathways are targets for the development of possible effective AD therapies. This review first updates strategies aimed at the inhibition of Abeta formation and then discusses the role of food-derived polyphenols as putative anti-amyloid drugs.


Numerical responses by populations of red fox and mountain hare during an outbreak of sarcoptic mange.
During a severe outbreak of sarcoptic mange (Sarcoptes scabiei vulpes) starting among red foxes (Vulpes vulpes) in Sweden in the 1970s, we studied: 1) the establishment and spread of the disease in northernmost Sweden (by inquiries), and 2) the 1970-84 bag records for foxes and mountain hares (Lepus timidus) (an alternative prey to the fox's main prey, voles). Since the first case of sarcoptic mange in 1975 the disease spread rapidly, with >50% of the hunting organizations having reported the disease in 1981 and >75% in 1983. Also the disease became more abundant within the areas affected. In areas with a low mange infection rate (index) the number of foxes killed in the 1980s did not deviate markedly from the average level in the 1970s. However, there was a slight tendency towards a decline in areas with a medium index and numbers declined markedly where the index was high. Hare harvests initially were low (after a tularemia epidemic) in the 1970s. In that decade harvests increased dramatically and stabilized, increased gradually or changed little, respectively, where mange infection rates were low, medium or high in the early 1980s. In areas with a low mange index hare harvests remained cyclical and at the same level in the 1980s as in most of the 1970s. However, in areas with a medium index harvests increased and seemed to begin to lose their cyclicity, and where the index was high the low and relatively stable hare harvests increased annually. A predator-prey hypothesis, assuming predators to synchronize alternative prey declines to those of the cyclic main prey, predicts that a predator reduction would cause a gradual disappearance of the cyclicity and increasing numbers among alternative prey. Our hare data are partially consistent with this prediction.


Experience with the AO method in the treatment of 142 cases of fresh fracture of the tibial shaft treated in the UK.
A prospective study was carried out on 142 fresh fractures of the tibial shaft treated by internal fixation according to the AO principles, 99 fractures being closed and 43 open. A total of 140 cases was reviewed at 1 year and 125 cases at 2 years following injury, at which times a functional assessment score was awarded by the surgeon and the patient himself, and a precise measurement of ankle range was made. The time taken for the fracture to unite and the incidence of non-union was greater if the fracture was comminuted (whether open or closed) than if there was no comminution. For patients with closed fractures the minor infection rate (erythema and increased local temperature) was 4.1 per cent and the major infection rate (pus present) was 4.1 per cent, no infection being severe enough to warrant removal of the plate. In open fractures, the overall infection rate was 14 per cent, 7 per cent having major infection and only 1 case requiring removal of the plate. The functional results and complications are discussed.


Segmental wall motion abnormalities in dilated cardiomyopathy: hemodynamic characteristics and comparison with thallium-201 myocardial scintigraphy.
This study assessed the hemodynamic characteristics of segmental wall motion abnormality of the left ventricle in patients with dilated cardiomyopathy (DCM) and its relation to the thallium-201 (TI-201) myocardial scintigraphy (MPI). Left ventriculograms and MPI in 23 patients were analyzed by the use of quantitative indexes of regional wall motion and TI-201 uptake based on a mean and a standard deviation of 13 normal subjects. Relative normokinesis in our definition was more frequently seen in the inferior wall than in the anterior wall (p less than 0.01). In contrast, severe asynergy was more often seen in the anterior wall than in the inferior wall (p less than 0.01). There were 11 patients who had relative normokinesis and asynergy together. By means of the index of wall motion, the DCM patients were divided into two groups, one with segmental wall motion abnormality (SWMA) and another with diffuse wall motion abnormality (DWMA). The DWMA group had higher left ventricular end-diastolic pressures (p less than 0.05) and the tendency of large left ventricular end-diastolic volumes than the SWMA group. There was a rough correlation (r = 0.58) between the quantitative indexes of TI-201 uptake and wall motion at the same region of the left ventricle. Thus, the nonuniformity of the left ventricular wall motion was recognized in the patients with DCM and more increased preload was shown in the patients with DWMA than in the group with SWMA. Further, the regional asynergy may be related to the localized fibrosis within the left ventricle in DCM, considering the result that the worse TI-201 uptake was roughly accompanied by the more severe asynergy.


Granular honeycomb scaffolds composed of carbonate apatite for simultaneous intra- and inter-granular osteogenesis and angiogenesis.
Granular porous calcium phosphate scaffolds are used for bone regeneration in dentistry. However, in conventional granules, the macropore interconnectivity is poor and has varying size. Herein, we developed a productive method for fabricating carbonate apatite honeycomb granules with uniformly sized macropores based on extrusion molding. Each honeycomb granule possesses three hexagonal macropores of ∼290 μm along its diagonal. Owing to these macropores, honeycomb granules simultaneously formed new and mature bone and blood vessels in both the interior and exterior of the granules at 4 weeks after implantation. The honeycomb granules are useful for achieving rapid osteogenesis and angiogenesis.


Overview on menopause.
Postmenopausal women comprise an ever-increasing percentage of the population. The alteration in ovarian function with loss of cyclic hormonal activity after menopause appears to be an actual endocrinopathy that produces definite metabolic effects. Clinicians must therefore become able to differentiate postmenopausal endocrine changes from those associated with the aging process. Four criteria are necessary for endocrinopathy to be present: morphologic changes, functional changes, hormonal changes, and target-tissue changes. The metabolic and pathologic changes after menopause appear to satisfy these criteria. If an actual endocrinopathy is determined to be present, long-term hormonal replacement therapy may be appropriate.


A case of association between type I hyperlipoproteinemia and systemic lupus erythematosus (SLE). Effects of steroid treatment.
The case of a girl aged 19 yr with hypertriglyceridemia and systemic lupus erythematosus (SLE) is described. The girl had been admitted to a Lipid Outpatient Clinic in 1981 and diagnosed as having a Type I hyperlipidemia pattern. In November 1984 the patient acutely developed a SLE syndrome. Steroid treatment led to a dramatic fall of serum triglycerides from a starting value of 2100 mg/dl to 95 mg/dl. The role of steroids in completely correcting genetically deficient Lipoprotein Lipase Activity (LLA) is discussed.


Metabolism of an aromatic retinoid Ro 10-9359 by cultured human epidermal keratinocytes.
An aromatic retinoid Ro 10-9359 is metabolized after absorption from intestine to form Ro 10-1670 which is an active therapeutic compound. The epidermal keratinocytes, a main target tissue of retinoid therapy in dermatology, was examined in the capacity to metabolize the retinoid. The culture of human epidermal keratinocytes was treated with 10(-6) M Ro 10-9359 and the metabolites released in the medium was analyzed by HPLC. The HPLC profile showed a distinct peak of Ro 10-1670. The human skin fibroblasts, HeLa cells. Chang liver cells and 3T3 cells were less active in metabolizing Ro 10-9359, and only a small amount of Ro 10-1670 was detected in the culture of human skin fibroblasts treated with 10(-6) M Ro 10-9359 for 2 days. When these cells were disrupted by a glass homogenizer, and incubated with Ro 10-9359, no Ro 10-1670 formation was detected.


Health-Related Quality of Life in Adolescents and Young Adults with Polycystic Ovary Syndrome: A Systematic Review.
To review recent data exploring the relationship between polycystic ovary syndrome (PCOS) and health-related quality of life (HRQoL) in adolescents and its implication for management of adolescents with this syndrome. We performed a systematic literature search in MedLine, Embase and PsychInfo from 1980 to September 2015 and manual search in reference lists of selected articles. Inclusion criteria were articles in English or French with a focus on HRQoL in patients with PCOS aged between 13 and 24 years. Qualitative, cross-sectional, or interventional studies were considered as eligible. Two reviewers each independently selected and reviewed the relevant articles. Of a total of 93 publications, 7 were selected through a systematic search, and 2 were added after a manual search. Seven studies used quantitative methods and 2 studies used a qualitative one. A meta-analysis was not possible because of the methodological diversity among the selected articles. All articles showed that PCOS has a negative influence on HRQoL in adolescents. Body weight issues and body mass index (BMI) appeared to have the strongest effect on HRQoL; some studies reported a normalization of HRQoL scores after adjustment for BMI. Patient information and patient-provider relationship were also reported to affect HRQoL. Elements in favor of the effectiveness of multidisciplinary management, associated lifestyle modifications, and psychological support, in improving HRQoL were identified. PCOS significantly reduces HRQoL in adolescent girls. The extent to which body weight issues and BMI mediate this effect deserves further evaluation. A detailed understanding of the psychosocial challenges that patients with PCOS face is limited, mainly because of the small number of studies available, restricted sample size, and the methodological diversity of the questionnaires used. The effect of early lifestyle modification, and medical and psychological treatment should continue to be explored.


Eu(III) and Am(III) adsorption on aluminum (hydr)oxide minerals: surface complexation modeling.
Americium is a highly radioactive actinide element found in used nuclear fuel. Its adsorption on aluminum (hydr)oxide minerals is important to study for at least two reasons: (i) aluminum (hydr)oxide minerals are ubiquitous in the subsurface environment and (ii) bentonite clays, which are proposed engineered barriers for the geologic disposal of used nuclear fuel, have the same ≡AlOH sites as aluminum (hydr)oxide minerals. Surface complexation modeling is widely used to interpret the adsorption behavior of heavy metals on mineral surfaces. While americium sorption is understudied, multiple adsorption studies for europium, a chemical analog, are available. In this study we compiled data describing Eu(III) adsorption on three aluminum (hydr)oxide minerals-corundum (α-Al2O3), γ-alumina (γ-Al2O3) and gibbsite (γ-Al(OH)3)-and developed surface complexation models for Eu(III) adsorption on these minerals by employing diffuse double layer (DDL) and charge distribution multisite complexation (CD-MUSIC) electrostatic frameworks. We also developed surface complexation models for Am(III) adsorption on corundum (α-Al2O3) and γ-alumina (γ-Al2O3) by employing a limited number of Am(III) adsorption data sourced from literature. For corundum and γ-alumina, two different adsorbed Eu(III) species, one each for strong and weak sites, were found to be important regardless of which electrostatic framework was used. The formation constant of the weak site species was almost 10,000 times weaker than the formation constant for the corresponding strong site species. For gibbsite, two different adsorbed Eu(III) species formed on the single available site type and were important for the DDL model, whereas the best-fit CD-MUSIC model for Eu(III)-gibbsite system required only one Eu(III) surface species. The Am(III)-corundum model based on the CD-MUSIC framework had the same set of surface species as the Eu(III)-corundum model. However, the log K values of the surface reactions were different. The best-fit Am(III)-corundum model based on the DDL framework had only one site type. Both the CD-MUSIC and the DDL model developed for Am(III)-γ-alumina system only comprised of one site type and the formation constant of the corresponding surface species was ~ 500 times stronger and ~ 700 times weaker than the corresponding Eu(III) species on the weak and the strong sites, respectively. The CD-MUSIC model for corundum and both the DDL and the CD-MUSIC models for γ-alumina predicted the Am(III) adsorption data very well, whereas the DDL model for corundum overpredicted the Am(III) adsorption data. The root mean square of errors of the DDL and CD-MUSIC models developed in this study were smaller than those of two previously-published models describing Am(III)-γ-alumina system, indicating the better predictive capacity of our models. Overall, our results suggest that using Eu(III) as an analog for Am(III) is practical approach for predicting Am(III) adsorption onto well-characterized minerals.


Challenges & opportunities for phage-based in situ microbiome engineering in the gut.
The gut microbiome is a promising target for the development of GI tract therapies, yet it has been under-exploited due, in part, to a lack of tools to control and manipulate complex microbial communities. To date, the most common approach in harnessing bacteria for therapeutic purposes has been to deliver ex vivo engineered bacteria-effectively taking a bacterial cell therapy-based approach. An alternative approach involves taking advantage of the rich microbial ecosystem in the gut by genetically modifying the microbiome in situ through the use of engineered bacteriophages-akin to human gene therapies delivered by viral vectors. In this review, we present the challenges and opportunities associated with engineering bacteriophages to control and manipulate the gut microbiome.


[The use of a method of mathematical analysis in establishing the species affiliation of animal hair].
Quantitative content of 10 trace elements in hair of 9 species of animals was determined by atomic-absorbtion spectroscopy. Analysis of the resulting digital data using discriminant algorithm makes it possible to determine species and sex of an animal by trace element content of hair.


A model for the weathering of Colombian crude oils in the Colombian Caribbean Sea.
A model that describes the weathering of crude in an oil spill caused by interaction with the atmosphere and the ocean was developed. This model was adapted to the Colombian crudes Cusiana (°API43.2) and Vasconia (°API20.7). To calibrate the model, evaporation and emulsification experiments were carried out at conditions similar to those of an oil spill in the Colombian Caribbean Sea. The dependence of evaporation with wind velocity, not predicted by the state-of-the-art models, was captured by a correlation for the mass transfer coefficient calculated from the experimental data. Emulsification rate, maximum water content and required evaporation to form an emulsion were determined and their values explained considering the effect of wax precipitation for Cusiana crude oil. When compared to well-established weathering software, such as ADIOS, the proposed model predicts the weathering of Colombian oils in a way that better agrees with the experiments conducted in the laboratory.


Is God a Placebo?
Every treatment, in classical no less than in unorthodox medicine, includes a so-called 'placebo' component. Such ingredients are more accurately described as non-specific factors (NSF), for several reasons, including the fact that they are not invariably pleasing. The purpose of the title of this contribution is to provoke a discussion of NSF, leading to their classification and the description of a quantitative method (based on Judgment Analysis) of estimating the amount of 'placebo-ness', or 'non-specificity', attributable to any treatment, whether surgical or intercessory prayer.


Current knowledge on evidence-based shockwave treatments for shoulder pathology.
Shoulder pain is one of the most common musculoskeletal pathologies. Treatment by ESWT (extracorporeal shockwave therapy) has emerged as an alternative when conservative treatment fails in rotator cuff calcific tendinopathy, prior to invasive procedures. The clinical efficacy of ESWT in non-calcific tendinopathy remains controversial. The good results in the treatment of rotator cuff calcifications, have led to indications of ESWT being expanded to other shoulder pathologies. We review the current state of indications and evidence based practice.


Carbonic Anhydrase Inhibitors. Part 46 Inhibition of Carbonic Anhydrase Isozymes I, II and IV With Trifluoromethylsulfonamide Derivatives and Their Zinc(II) and Copper(II) Complexes.
Reaction of aromatic/heterocyclic sulfonamides containing a free amino group with triflic anhydride afforded compounds possessing trifluoromethanesulfonamido moieties in their molecule. The Zn(II) and Cu(II) complexes of these new sulfonamides were prepared and characterized by standard procedures (elemental analysis, spectroscopic, magnetic, thermogravimetric and conductimetric measurements). The new derivatives showed good inhibitory activity against three isozymes of carbonic anhydrase (CA), i.e., CA I, II and IV.


Development of children with early cytomegalovirus infection.
To find out whether cytomegalovirus (CMV) infection during the first months of life influences child development, developmental assessment at the age of 2 years was performed on 116 Finnish children chosen at random in a maternity hospital and followed from birth for the occurrence of CMV infection. Two of the children had congenital infection and 39 were infected after birth but before the age of 6 months. Another five children were infected between the ages of 6 and 12 months, and 70 remained non-infected. The developmental assessment, based principally on the Denver Development Screening Test (DDST), included 7 items for gross motor skills, 6 items for fine motor skills, and 4 items for language development. Significantly more perinatally infected children (7/39) were delayed in speech, compared with the non-infected children (3/70). Furthermore, some items assessing fine motor development were passed better by the non-infected than the perinatally infected children, but the difference in total score was not significant. The performance of the two children with congenital CMV infection did not differ from that of the non-infected children.


Pharmacological and biochemical properties of isomeric yohimbine alkaloids.
The stereochemical and pharmacological properties of yohimbine and some of its isomers are briefly reviewed. Several pharmacological and physical properties of a selection of the isomers have been determined with a view to elucidating which might be important in the elaboration of the known behavioral effects produced by them. Activity is not dependent upon lipid solubility or on the ease of access to the central nervous system. The isomers are weak inhibitors of rat-brain acetylcholinesterase and weak antagonists at muscarinic cholinergic receptors. In the rat brain in vitro they do not possess significant monoamine oxidase-inhibiting properties nor do they inhibit the uptake of serotonin. They are relatively potent antagonists of 5HT on the rat isolated fundus preparation and their potency in this preparation may be related to their ability to produce behavioral and cardiovascular effects in man and dogs.


Delivering RNAi therapeutics with non-viral technology: a promising strategy for prostate cancer?
Prostate cancer is the most prevalent cancer in men of the United States and Europe, and although current treatments have efficacy in treating primary prostate cancer, they are associated with a decreased quality of life and are ineffective in treating the metastatic disease. The identification of oncogenes associated with the formation, proliferation, and metastasis of prostate cancer has presented promising targets for RNA interference (RNAi)-based gene therapy. However, the potential of RNAi as a successful therapeutic depends on effective delivery. In this review, we discuss the potential of targeting oncogenes implicated in prostate cancer with RNAi-based therapeutics using non-viral bioresponsive 'smart' delivery systems that work in harmony with the physiological and biochemical environments of prostate tumours.


Binocular visual form deprivation in human infants.
Visual acuity was measured with a preferential looking technique in infants and toddlers with binocular form deprivation. Of the 10 children in the study, there were 5 with congenital cataracts and 5 with uncorrected high refractive errors. Infants with cataract surgery before 2 months of age showed normal early development of visual acuity. A 4 to 6 month delay before treatment resulted in reduced acuity but recovery subsequently occurred. Infants with high hyperopia or astigmatism showed no acuity deficits in the first year of life when tested with optical correction. One case of early meridional amblyopia was detected in the third year of life. The deficit was not permanent and, after a period of optical correction, there was recovery of visual acuity to normal levels.


Dual effects of bradykinin on prostaglandin metabolism: relationship to the dissimilar vascular actions of kinins.
Generation of a prostaglandin of the F series by bovine mesenteric veins in response to bradykinin may depend on increased synthesis of PGE and conversion of the latter to PGF after activation of PGE 9-ketoreductase by the kinin. The prostaglandin then mediates the constrictor action of bradykinin on the bovine mesenteric vein. A high speed supernatant (HSS) fraction of bovine mesenteric blood vessels contains the highest activity of PGE 9-ketoreductase. Incubation of PGE2 with HSS at 37 degrees C in the presence of a NADPH generating system resulted in time-dependent conversion of PGE2 to PGF2alpha. Bradykin (0.01mM) more than doubled conversion of PGE2 to PGF2alpha by the PGE 9-ketoreductase obtained from mesenteric veins whereas the kinin had little effect on enzymic activity of the HSS fraction of mesenteric arteries. However, after inhibition of kininase catabolism, bradykinin increased PGE 9-ketoreductase activity of arteries and veins to the same degree. Prostaglandin release from veins by bradykinin appears essential to contraction of mesenteric venous strips evoked by the polypeptide as indomethacin treatment abolished this effect. PGE 9-ketoreductase may be an important prostaglandin regulatory mechanism of the vascular wall whereby the functional consequences of changes in rates of prostaglandin synthesis are governed by determining the ratio of PGE to PGF within vascular tissue. Constriction of bovine mesenteric veins evoked by bradykinin may, therefore, depend on increased prostaglandin synthesis and conversion of newly formed PGE to PGF, both steps being affected by the kinin.


Preparing for the American Board of Surgery Flexible Endoscopy Curriculum: Development of multi-institutional proficiency-based training standards and pilot testing of a simulation-based mastery learning curriculum for the Endoscopy Training System.
The Fundamentals of Endoscopic Surgery (FES) exam is required for American Board of Surgery certification. The purpose of this study was to develop performance standards for a simulation-based mastery learning (SBML) curriculum for the FES performance exam using the Endoscopy Training System (ETS). Experienced endoscopists from multiple institutions and specialties performed each ETS task (scope manipulation (SM), tool targeting (TT), retroflexion (RF), loop management (LM), and mucosal inspection (MI)) with scores used to develop performance standards for a SBML training curriculum. Trainees completed the curriculum to determine feasibility, and effect on FES performance. Task specific training standards were determined (SM-121sec, TT-243sec, RF-159sec, LM-261sec, MI-180-480sec, 7 polyps). Trainees required 29.5 ± 3.7 training trials over 2.75 ± 0.5 training sessions to complete the SBML curriculum. Despite high baseline FES performance, scores improved (pre 73.4 ± 7, post 78.1 ± 5.2; effect size = 0.76, p > 0.1), but this was not statistically discernable. This SBML curriculum was feasible and improved FES scores in a group of high performers. This curriculum should be applied to novice endoscopists to determine effectiveness for FES exam preparation.


Radiofrequency thermal ablation: increase in lesion diameter with continuous acetic acid infusion.
To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance, and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 +/- 2.1 mm (RF only), 29.2 +/- 4.8 mm (RF + saline 0.9%) and 30.7 +/- 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.


Ferrous-based electrolyte for simultaneous NO absorption and electroreduction to NH3 using Au/rGO electrode.
Electrochemical reduction of NO to NH3 (NORR) is an attractive approach to mildly realize NO removal and valuable NH3 production. The electrolyte, as function as the NO absorbent, is crucial to apply electrochemical technology in practical de-NO engineering. In this paper, the ferrous chelate acted as the electrolyte for effective NO absorption in NORR based on the Brown-ring reaction. The rGO and Au/rGO catalysts served as cathodes to realize ferrous regeneration for continuous NO reduction. The results revealed that ferric chelate could be fully reduced at lower onset potential on rGO electrode. The Au/rGO catalyst exhibited excellent average yield and selectivity for NH3 at - 0.1 V and pH = 6.32, (14.6 μmol* h-1 * cm-2 and 65.2%, respectively). The Faradaic Efficiency of NH3 could reach 98.3% at pH = 1.0. This work provides a valuable reference for effective NO adsorption and sustainable NO-to-NH3 conversion.


Reduced graphene oxide-zinc oxide nanocomposite as dispersive solid-phase extraction sorbent for simultaneous enrichment and purification of multiple mycotoxins in Coptidis rhizoma (Huanglian) and analysis by liquid chromatography tandem mass spectrometry.
In the current study, a robust dispersive solid-phase extraction (dSPE) strategy using reduced graphene oxide-zinc oxide (rGO-ZnO) nanocomposite as the sorbent was proposed for separation, purification and enrichment of 12 mycotoxins in Coptidis rhizoma (Huanglian). The targeted mycotoxins included aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, alternariol-methylether, mycophenolic acid, ochratoxin A, penitrem A, nivalenol, zearalenone and zearalanone. The rGO-ZnO nanocomposite was successfully synthesized through hydrothermal process by a modified Hummers method, and further characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), FTIR spectroscopy, ultraviolet-visible spectroscopy and X-ray diffraction (XRD). Several key parameters affecting the performance of the dSPE approach were extensively investigated, and after optimization, acetonitrile/water/formic acid (80/19/1, v/v/v) as the extraction solution, 2% acetonitrile as the adsorption solution, 15 mg rGO-ZnO as the sorbent, n-hexane as the washing solution, and methanol/formic acid (99/1, v/v) as the desorption solution presented an excellent purification and enrichment efficiency. Under the optimal dSPE procedure followed by analysis with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), adequate linearity (R2 ≥ 0.991), high sensitivity (limit of quantification in the range of 0.09-0.41 µg kg-1), acceptable recovery (70.3-105.7%) and satisfactory precision (RSD 1.4-15.0%) were obtained. The analysis of 12 selected mycotoxins was also carried out in real Coptidis rhizoma (Huanglian) samples for applicability evaluation of the established method.


Standardised or individualised X-ray tube angle for mediolateral oblique projection in digital mammography?
We aimed to investigate whether there were any differences in positioning criteria related to the presentation of the pectoralis major muscle (pectoral muscle) for women of different heights using a standardized 60° X-ray tube angle for mammograms in mediolateral oblique (MLO) projection. Data from MLO mammograms of right breasts of 45,193 women screened in BreastScreen Norway 2016-2019 were used. The positioning criteria were related to the pectoral muscle length (measure A and measure B), width and shape and considered adequate or inadequate depending on the degree of fulfilling the criteria. Data associated with the pectoral muscle were extracted from Volpara, an automated software for breast density assessment. Information on height was obtained from a self-reported questionnaire received by the women together with the invitation to attend the screening program. Women were divided into three groups based on the height percentiles (P) in the Norwegian growth curves: < 25th percentile (<P25th: ≤163 cm), 25th-75th percentile (P25-P75th: 164-170 cm), and >75th percentile (>P75th: >170 cm). Logistic regression was used to analyse the odds of adequate pectoral muscle length A and B, and shape, adjusting each model for screening technique and equipment model. Results were presented with odds ratios (OR) and 95% confidence intervals (CI). Mean age of the screened women was 61.5 (SD = 4.8) years. The adequate measure for the pectoral muscle length A was obtained for 25.9% (11,724/45,193), length B for 76.3% (34,489/45,193), width for 75.0% (33,894/45,193) and shape for 97.6% (44,118/45,193) of the mammograms. Adjusted odds of an adequate pectoral muscle length A were lower for women of <P25th (OR = 0.90, 95% CI: 0.86-0.95) compared to women of P25-75th. Odds of an adequate pectoral muscle length B were lower for women of <P25th (OR = 0.88, 95% CI 0.84-0.93) and higher for women of >P75th (OR = 1.08, 95% CI 1.02-1.14) compared to women of P25-75. Odds of an adequate pectoral muscle shape were higher for women of <P25th (OR = 1.14, 95%CI 1.08-1.19) and lower for women of >P75th (OR = 0.92, 95% CI 0.87-0.97) compared to women of P25-75th. The 60° X-ray tube angle might suit most of the female population offered mammographic screening in Norway, but women of a relatively low height (163 cm or lower) might benefit from an X-ray tube angle less than 60-degrees. Using 60° X-ray tube angle for the MLO mammograms in BreastScreen Norway fit the majority of the participating women. More research is needed to change the protocol associated with the tube angle for women shorter than 163 cm.


A Review of Disparities in Cannabis Use and Cannabis Use Disorder Affecting Sexual and Gender Minority Populations and Evidence for Contributing Factors.
Sexual and gender minorities (SGM) appear to be at elevated risk for cannabis use (CU) and cannabis use disorder (CUD) compared to cisgender heterosexuals. However, risk factors remain understudied among SGM. This review aims to summarize evidence for disparities in CU and CUD affecting SGM and factors contributing to these disparities. We found strong evidence that sexual minorities are at elevated risk for CU and CUD is elevated for sexual minority women. Evidence supports a concurrent association between minority stress and CUD symptoms. There is robust support for coping motives as a mechanism linking minority stress to subsequent CU and CUD. Studies also point to CU norms and contexts as potential risk factors. SGM are at high risk for CU and CUD, and minority stress, CU norms, and contextual factors are implicated. Additional research is needed on CU among gender minorities, prospective effects of risk factors, and interventions for SGM.


Risk Factors of Hypoxemia in the Postanesthesia Care Unit After General Anesthesia in Children.
To investigate the incidence and risk factors of hypoxemia in the postanesthesia care unit (PACU) after general anesthesia in children. A retrospective observational study. Elective surgical patients (N = 3,840 patients) treated in a pediatric hospital were divided into a hypoxemia group and a nonhypoxemia group according to the presence of hypoxemia following transport to the PACU. The clinical data of the 3,840 patients were compared between these two groups to evaluate factors that were linked to the development of postoperative hypoxemia. Factors that showed a statistically significant difference (P < .05) in single-factor tests were then examined in multivariate regression analyses to identify hypoxemia risk factors. In our study group of 3,840 patients, 167 (4.35%) patients developed hypoxemia, with an incidence of 4.35%. Univariate analysis indicated that age, weight, anesthesia method, and operation type were significantly associated with hypoxemia. Logistic regression analysis indicated that operation type was associated with hypoxemia. Surgery type is a primary risk factor for pediatric hypoxemia in the PACU following general anesthesia. Patients undergoing oral surgery are more prone to hypoxemia and should be more intensively monitored to ensure timely treatment if required.


[Analysis of the binding capacity of the benzodiazepine site of gabaa receptor in mice C57BL/6 and BALB/C pretreated with anxiolytics].
The level of specific 3H-flunitrazepam binding in synaptosomal membranes of C57BL/6 and BALB/c mice brain underwent to the stress of different types has been studied. Mild stress (Elevated Plus Maze) was shown to induce the decrease of benzodiazepine binding in BALB/c mice only, while the strong one (Exposure to a predator) was revealed to cause this decrease in both strains. Behavioral effects of different non-benzodiazepine drugs possessing anxiolytic properties (Afobazol, Ladasten and Noopept) was accompanied with the normalization of the level of benzodiazepine reception, reduced by the stress of both modalities.


Stimulation of G2-arrested rat liver and pancreas cells by fasting.
The present study complements earlier work that revealed a mitogenic effect of fasting on G2-blocked hepatocytes, demonstrating that the release of hepatocytes from the G2 arrest is maximal at 3 h of fasting and that the phenomenon lasts for 12 h. The mitogenic effect of fasting is not restricted to the liver, as similar results were obtained with the pancreas--suggesting a possible action on other organs as well. A simple physiologic stimulus such as fasting can thus be used in further studies on the properties of G2 cell populations and their possible role in the regulation of normal and abnormal growth processes.


Late-Onset Radial Nerve Palsy in the Setting of Humeral Shaft Hypertrophic Nonunion: A Case Report.
A 67-year-old woman presented 9 months after a closed midshaft humerus fracture with a new onset radial nerve palsy. Radiographs demonstrated a hypertrophic nonunion. Upon exploration, the radial nerve was in continuity and entrapped in fracture callus. It was extricated from the callus, and an open reduction and plate fixation was performed. Full radial nerve function returned by 3 months. We recommend that delayed onset radial nerve palsies be treated on a semiurgent basis with radial nerve exploration and decompression followed by internal fixation to achieve primary bone healing and minimize fracture callus formation.


T cell control of primary and latent cytomegalovirus infections in healthy subjects.
The T cell repertoire required to control acute and latent CMV infection in otherwise healthy individuals was examined using both functional analysis and a wide range of MHC I tetramers. Both frequency and function of CMV specific T cells varied considerably between subjects, however, within subjects values remained stable over time. In total 16 +/- 3.5 CMV specific T cells/mul blood was detected, with obvious immunodominance between different CMV epitopes. Most subjects with latent infection showed low CMV specific T cell activity, whereas a subgroup (1/3) of individuals was high in either frequency or function of their CMV specific T cells. Patients with acute infection displayed high initial, but rapidly decreasing, numbers of CMV specific cells. In conclusion, a majority of healthy individuals readily seem to control latent CMV infection, whereas a subpopulation (1/3) of individuals uses a large proportion of their CD8+ T cell repertoire to control the infection.


Transforming growth factor-β1-gene polymorphism in the development of kidney disease after liver transplantation.
The development of kidney dysfunction is one of the most important after liver transplantation (LT). Genetic variants of pathogenetically relevant cytokines may influence the development and course of the disease. The aim of our study was to evaluate the role of transforming growth factor-β1 (TGF-β1) polymorphism in this context. Four hundred eighty-six liver graft recipients were genotyped for TGF-β1 codon 25 (guanine → cytosine, G → C) by polymerase chain reaction. Renal function before and after LT was characterized by estimation of glomerular filtration rate (GFR) using four-parameter-modification of diet in renal disease formula on defined dates. GFR was compared among TGF-β1-genotype groups of the entire cohort within the median observation period of 7 years. For the assessment of renal function recovery after LT, patients were divided into three groups by GFR difference (ΔGFR = ± 10 mL/min). Mean pretransplant GFR differed significantly among TGF-β1-genotype groups (GG: 85.0 mL/min vs. GC/CC: 75.3 mL/min; P=0.016). The significance disappeared in the follow-up period. Although GG genotype demonstrated higher mean GFR levels, patients with GC/CC genotype tended to improve kidney function compared with GG genotype (P=0.013). Interestingly, lower mean GFR rates were observed among female compared with male recipients before (P=0.002), separately at all dates and cumulatively after LT (P<0.001). Genetic variants of one of the most important cytokine TGF-β1 at codon 25 may have an impact on kidney function, suggesting an unfavorable effect of C allele in pretransplant setting and serve as marker for the recovery of renal function after LT. The identification of further confounders seems to be promising.


Association of JAG1 gene polymorphism with systemic blood pressure in patients with obstructive sleep apnea: a prospective cohort study.
To assess the effects of single nucleotide polymorphisms (SNPs) on blood pressure control in patients with obstructive sleep apnea (OSA). This prospective observational cohort study, conducted between 2004 and 2014, examined the associations of SNPs of JAG1, GUCY1A3-GUCY1B3, SH2B3, and NPR3-C5orf23 genes with systolic and diastolic blood pressure (SBP, DBP) in 1179 adults evaluated for OSA with overnight polysomnography. Genotyping was performed by unlabeled probe melting analysis. The patients were predominantly male (69.6%, mean age 52±11 years, apnea-hypopnea index 34±31 episodes/h). Only JAG1 genotype was associated with SBP and DBP: compared with AA homozygotes, G allele carriers (pooled GG and AG genotype) had significantly higher morning SBP (132±19 vs 129±18 mm Hg; P=0.009) and morning and evening DBP (85±11 vs 83±10 mm Hg, P=0.004; 86±10 vs 84±10 mm Hg, P=0.012, respectively); the differences remained significant after the correction for multiple SNPs testing. In multivariate analyses, oxygen desaturation index and JAG1 genotype independently predicted morning SBP (P=0.001, P=0.003, respectively) and DBP (P<0.001, P=0.005, respectively), and evening SBP (P=0.019, P=0.048, respectively) and DBP (P=0.018, P=0.018, respectively). This is the first replication study of the SNPs recently linked to arterial hypertension in general population by genome-wide association studies. Our findings suggest that JAG1 genotype is related to blood pressure control in OSA: G allele was associated with higher morning and evening SBP and DBP.


Patients seeking liver transplant turn to China: outcomes of 15 Egyptian patients who went to China for a deceased-donor liver transplant.
Increasing numbers of Egyptians with end-stage liver disease seek liver transplants in China because of lower costs and shorter wait times.We evaluated outcomes of Egyptian patients who underwent liver transplants in China and address ethical concerns. Fifteen Egyptian patients (11 men, 4 women; mean age, 52 years) who underwent liver transplants in China were included. Preoperative data before traveling to China, reports from China, and follow-up data upon return were reviewed. Indications included hepatitis-C-related liver cirrhosis (n=9), hepatitis-C-related liver cirrhosis with hepatocellular carcinoma (n=4), and hepatitis-B-related liver cirrhosis (n=2). Nine patients were evaluated for living-related liver transplant but none of their potential donors was suitable. Three patients had advanced hepatocellular carcinoma and were not accepted for living-related liver transplant by any Egyptian center. Two patients had no living-related donor. One patient refused a living-related liver transplant in Egypt and elected to get a whole liver graft from China. Overall survival rate was 80.0% at 6 months and 73.3% at 12 months. There were 4 deaths; 2 occurred in China. Of the 11 surviving patients, 9 (82%) developed complications. Nineteen complications were seen in the 13 patients who were managed after returning from China. Major complications necessitating prolonged hospitalizations occurred in 4 patients. Two patients required further laparotomy. Although deceased-donor liver transplant in China could be an option for Egyptian patients with end-stage liver disease, patients and clinicians should be aware of potential outcomes and related ethical issues.


Do Indomethacin or Radiation for Heterotopic Ossification Prophylaxis Increase the Rates of Infection or Wound Complications After Acetabular Fracture Surgery?
To compare the rates of infection and wound complications in patients undergoing operative fixation (ORIF) of acetabular fractures receiving heterotopic ossification (HO) prophylaxis using indomethacin or external beam radiation therapy (XRT) versus no prophylaxis. Retrospective cohort. Level I trauma center. We reviewed 473 patients undergoing ORIF of acetabular fractures through posterior, combined, or extensile surgical approaches from 2012 to 2017, with a median follow-up of 13 months (0.5-77 months). Rates of infection and wound complications were stratified according to their HO prophylaxis method into three groups as indomethacin, XRT, and no prophylaxis. Overall, 167 patients (35.3%) received indomethacin, 104 patients (22.0%) received postoperative XRT, and 202 patients (42.7%) received no prophylactic treatment. There was no difference between the 3 groups for the risk of surgical site infection (P = 0.280). The XRT group had a significantly increased risk of noninfectious wound complications (20.2%) compared with the indomethacin group (6.6%, P = 0.002) and the no prophylaxis group (5.0%, P < 0.0001). Multivariate analysis revealed XRT remained a significant risk factor for noninfectious wound complications compared with no prophylaxis (odds ratio 5.39; 95% confidence interval 2.37-12.22; P < 0.0001). Although there is no difference between XRT, indomethacin, and no HO prophylaxis for the risk of surgical site infection, the use of XRT results in more than 5 times increased risk of noninfectious wound complications compared with no prophylaxis. This increased risk should be considered when contemplating XRT for HO prophylaxis in acetabular fracture patients. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Testing a psychosocial model of sexual communication and sexual risk-taking: A cross-sectional, online survey study of Australian University students.
Sexually transmitted infection rates are higher among young people relative to other age groups. Despite much investigation, there is not enough research about in-the-moment factors associated with risky sexual behaviour, such as relational and situational variables. The present study sought to test a comprehensive psychosocial model of sexual risk-taking that included a range of factors: individual (emotion dysregulation, impulsivity), relational (attachment, communication), societal (norms, gender), and situational (dating application use, alcohol use). 1244 young people aged 18 to 25 years (82.9 % women; 59.2 % single, 36.0 % in a monogamous relationship) participated in an online survey. The cross-sectional model was tested using Structural Equation Modelling. Sexual communication mediated the relationship between attachment anxiety and sexual risk. However, contrary to predictions, greater sexual communication was related to higher risk. Post-hoc analysis showed that this unexpected relationship may be due to the way sexual risk was measured, as an alternative model specifying casual unprotected sex as the outcome showed no positive relationship between sexual communication and risk. Findings indicate that young people with anxious attachment are less confident communicating about sexual health. Measures of sexual risk focusing on specific risk activities in context yield different findings to those assessing general sexual behaviours. Findings support interventions focusing on addressing perceived sexual risk norms and the dating application context to reduce risk.


Clinical impact of a PCR assay for identification of Staphylococcus aureus and determination of methicillin resistance directly from blood cultures.
We evaluated the clinical usefulness of a PCR assay that discriminates Staphylococcus aureus from coagulase-negative staphylococci and detects methicillin resistance on blood cultures by measuring the adaptation of antimicrobial therapy based on the PCR results. Only 7 of 28 patients (25%) benefited from a modification of antibiotic therapy based on the PCR results, since empirical therapy was appropriate in a majority of cases.


Structure, synthesis, and sensing applications of single-walled carbon nanohorns.
Single-walled carbon nanohorns (SWCNHs), a type of tapered carbon nanomaterials, are generally prepared by laser ablation method, arc method, and Joule heating method without the addition of metal catalysts, which makes them pure and environmentally friendly. The obtained aggregates of SWCNHs mainly have three different types of structure, dahlia-like, bud-like, and seed-like. Over the past few decades, they have been widely used in the fields of energy, medicine, chemistry, and sensing. The SWCNHs-based sensors have shown high sensitivity, rapid response, and excellent stability, which are mainly attributed to the excellent electrical conductivity, large electrochemical window, large specific surface area, and mechanical strength of SWCNHs. In this review, we systematically summarizes the structures, synthesis methods, and sensing applications of SWCNHs, including electrochemical sensors, photoelectrochemical sensors, electrochemiluminescence sensors, fluorescent sensors, and resistive sensors. Moreover, the development prospects of SWCNHs in this field are also discussed.


Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism.
One aim of systems toxicology is to deliver mechanistic, mathematically rigorous, models integrating biochemical and pharmacological processes that result in toxicity to enhance the assessment of the risk posed to humans by drugs and other xenobiotics. The benefits of such 'in silico' models would be in enabling the rapid and robust prediction of the effects of compounds over a range of exposures, improving in vitro-in vivo correlations and the translation from preclinical species to humans. Systems toxicology models of organ toxicities that result in high attrition rates during drug discovery and development, or post-marketing withdrawals (e.g., drug-induced liver injury (DILI)) should facilitate the discovery of safe new drugs. Here, systems toxicology as applied to the effects of paracetamol (acetaminophen, N-acetyl-para-aminophenol (APAP)) is used to exemplify the potential of the approach.


A wild bootstrap approach for the selection of biomarkers in early diagnostic trials.
In early diagnostic trials, particularly in biomarker studies, the aim is often to select diagnostic tests among several methods. In case of metric, discrete, or even ordered categorical data, the area under the receiver operating characteristic (ROC) curve (denoted by AUC) is an appropriate overall accuracy measure for the selection, because the AUC is independent of cut-off points. For selection of biomarkers the individual AUC's are compared with a pre-defined threshold. To keep the overall coverage probability or the multiple type-I error rate, simultaneous confidence intervals and multiple contrast tests are considered. We propose a purely nonparametric approach for the estimation of the AUC's with the corresponding confidence intervals and statistical tests. This approach uses the correlation among the statistics to account for multiplicity. For small sample sizes, a Wild-Bootstrap approach is presented. It is shown that the corresponding intervals and tests are asymptotically exact. Extensive simulation studies indicate that the derived Wild-Bootstrap approach keeps and exploits the nominal type-I error at best, even for high accuracies and in case of small samples sizes. The strength of the correlation, the type of covariance structure, a skewed distribution, and also a moderate imbalanced case-control ratio do not have any impact on the behavior of the approach. A real data set illustrates the application of the proposed methods. We recommend the new Wild Bootstrap approach for the selection of biomarkers in early diagnostic trials, especially for high accuracies and small samples sizes.


Management of Oral Sub Mucous Fibrosis Using Three Different Flaps: Superficial Temporal, Nasolabial Flap, Buccal Fat Pad Flap Along with Active Physiotherapy- A Comparative Study.
To assess the efficacy of different flaps along with active physiotherapy for comprehensive management of OSMF. A total of 33 patients of oral submucous fibrosis were admitted and surgically treated. All patients were diagnosed with bilateral oral submucous fibrosis of buccal mucosa. All the patients had advanced oral sub mucous fibrosis with interincisal distance less than 20 mm. Eleven patients were treated with buccal pad of fat, eleven with nasolabial flap and eleven patients were treated with temporo-parietal fascia flap. Physiotherapy was started from the 5th postoperative day and the patients were followed regularly for one year to measure maximum interincisal distance. There was a significant corelation between post-operative mouth opening and regular physiotherapy, exercise and quitting of the habit irrespective of type of reconstruction flap used. On the basis of the result obtained from this study, significant improvement in mouth opening was seen in patients who performed aggressive physiotherapy irrespective of the flap used. Thus we conclude along with the surgical treatment, post-operative physiotherapy and cessation of habit are of equal importance for good prognosis in OSMF patients.


Cryogenically frozen PEGylated liposomes and micelles: Water penetration and polarity profiles.
Poly(ethylene glycol) (PEG)-grafted lipid dispersions are widely investigated in fundamental and biotechnological research for their successful use in drug-delivery. Here, we consider mixtures of the bilayer-forming lipid dipalmitoylphosphatidylcholine (DPPC) with the micelle-forming lipid PEG:2000-phosphatidilethanolamine (PEG:2000-DPPE) fully hydrated in D2O and measured at 77 K. Electron Spin Echo Envelope Modulation and continuous wave Electron Paramagnetic Resonance of chain-labelled lipids are employed to detect the extent of solvent permeation and the environmental polarity, respectively, across the hydrocarbon regions of the lipid assemblies. Sigmoidal water penetration and polarity profiles are described in sterically stabilized liposomes (SSL) formed at submicellar content of PEG:2000-DPPE incorporated in DPPC. Compared to DPPC bilayers, SSL show increased hydrophobicity at both the polar/apolar interface and the chain termini, and a broader transition that is shifted toward the interface. Solvent exposure and polarity decrease on going down the chain in PEG:2000-DPPE micelles. However, compared to SSL, polymer-lipid micelles show higher solvent permeation at any chain segment and the chain termini are accessible to water. In any sample, heterogeneity is found in H-bond formation between the spin-label nitroxide groups and the solvent molecules. The results at cryogenic temperature add new insights into the biophysico-chemical characterization of PEGylated lipid dispersions.


Genes influence the amplitude and timing of brain hemodynamic responses.
In functional magnetic resonance imaging (fMRI), the hemodynamic response function (HRF) reflects regulation of regional cerebral blood flow in response to neuronal activation. The HRF varies significantly between individuals. This study investigated the genetic contribution to individual variation in HRF using fMRI data from 125 monozygotic (MZ) and 149 dizygotic (DZ) twin pairs. The resemblance in amplitude, latency, and duration of the HRF in six regions in the frontal and parietal lobes was compared between MZ and DZ twin pairs. Heritability was estimated using an ACE (Additive genetic, Common environmental, and unique Environmental factors) model. The genetic influence on the temporal profile and amplitude of HRF was moderate to strong (24%-51%). The HRF may be used in the genetic analysis of diseases with a cerebrovascular etiology.


Xanthogranuloma of the choroid plexus of lateral ventricle, presenting with parosmia and parageusia.
Xanthogranulomas of the choroid plexus are usually asymptomatic. We present a short case report of a 60-year-old male whose symptoms of parosmia and parageusia have been relieved following surgical removal of a xanthogranuloma situated in the right lateral ventricle. Previous case reports and correlation of symptomatology and pathology are discussed.


Crocetin improves the insulin resistance induced by high-fat diet in rats.
The amelioration of insulin resistance by treatment with crocetin is closely related to the hypolipidaemic effect. The present study is designed to clarify the insulin-sensitizing mechanism of crocetin by elucidating the mechanism of regulation of lipid metabolism by crocetin. Rats given a high-fat diet were treated with crocetin for 6 weeks before hyperinsulinaemic-euglycaemic clamp. 14C-palmitate was used as tracer to track the fate of non-esterified fatty acids or as substrate to measure beta-oxidation rate. Triglyceride clearance in plasma and lipoprotein lipase activity in tissues were tested. Content of lipids in plasma and tissues was determined. Real-time PCR was used to assay the level of mRNA from genes involved in non-esterified fatty acid and triglyceride uptake and oxidation. Crocetin prevented high-fat-diet induced insulin resistance (increased clamp glucose infusion rate), raised hepatic non-esterified fatty acid uptake and oxidation, accelerated triglyceride clearance in plasma, enhanced lipoprotein lipase activity in liver, and reduced the accumulation of detrimental lipids (DAG and long-chain acyl CoA) in liver and muscle. Genes involved in hepatic lipid metabolism which are regulated by peroxisome proliferator-activated receptor-alpha, were modulated to accelerate lipid uptake and oxidation. Through regulating genes involved in lipid metabolism, crocetin accelerated hepatic uptake and oxidation of non-esterified fatty acid and triglyceride, and reduced lipid availability to muscle, thus decreasing lipid accumulation in muscle and liver, and consequently improving sensitivity to insulin.


Intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients in the United States: A case control analysis.
Although observational studies have reported favorable clinical outcomes associated with intra-arterial thrombolysis as adjunct to mechanical thrombectomy, the cost and length of hospitalization associated with this intervention has not been studied. We analyzed the nationally representative data of the United States data from Nationwide Inpatient Sample (NIS) to compare hospitalization cost and duration in addition to other outcomes in patients receiving (n = 1990) with those not receiving intra-arterial thrombolysis (n = 1990) in acute ischemic stroke patients undergoing mechanical thrombectomy using a case control design matched for age, gender, and presence of aphasia, hemiplegia, neglect, coma/stupor, hemianopsia and dysphagia. There was no difference in the median hospitalization cost in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: $36,992 [28,361 to 54,336] versus $35,440 [24,383 to 50,438], (regression coefficient 2,485 [-1,947 to 6,917], p = 0.27). There was no difference in the median length of hospitalization in patients treated with intra-arterial thrombolysis compared with those not treated with intra-arterial thrombolysis: 6 days [3 to 10] versus 6 days [4 to 10], (regression coefficient -0.34 [-1.47 to 0.80], p = 0.56). There was no difference in odds of home-discharge (OR 1.02 95%CI 0.72-1.43, p = 0.93) or post-procedural intracranial hemorrhage (OR 1.16 95%CI 0.83-1.64, p = 0.39) between the two groups. We did not observe an increase in the cost or length of hospitalization associated with the use of intra-arterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients. If the ongoing randomized clinical trials demonstrate therapeutic efficacy in reducing death or disability, this intervention has a high likelihood of being beneficial overall.


Subcutaneous inflammation (infection?) after synovial rupture: a complication of a complication.
Six weeks after presumptive acute synovial rupture at the knee, a patient was admitted with cutaneous induration over the medial calf. Roentgenograms showed gas shadows within the involved area. A fluctuant area at the center of the indurated mass yielded a Corynebacterium species.


Six-month outcomes of HIV-infected patients given short-course fluconazole therapy for asymptomatic cryptococcal antigenemia.
In HIV-infected adults in sub-Saharan Africa, asymptomatic cryptococcal antigenemia at the time of antiretroviral therapy (ART) initiation is associated with more than 20% increased mortality. Provisional recommendations for treatment of asymptomatic cryptococcal antigenemia are neither well substantiated nor feasible in many resource-poor settings. After hospitals in Tanzania implemented a programme providing serum cryptococcal antigen (CrAg) screening with 4-week intensive fluconazole treatment for CrAg-positive patients, we were asked to assess the impact of this programme on mortality. In this retrospective operational research study, we documented 6-month outcomes of HIV-infected adults who had had CD4 cell counts less than 200 cells/μl at the time of starting ART and had been screened for cryptococcal antigenemia over a period of 15 months. We randomly selected three CrAg-negative patients, matched for ART start date, for every CrAg-positive patient who had been identified and treated with the 4-week intensive fluconazole course. The primary outcome was 6-month mortality in CrAg-positive and CrAg-negative groups. Mortality of CrAg-positive HIV-infected adults who received short-course fluconazole was noninferior to CrAg-negative adults. At 6 months, 16 of 18 CrAg-positive and 46 of 54 CrAg-negative patients were alive [88.9% versus 85.1%, -3.9% absolute difference (one-sided 90% confidence interval +10.8%)]. No deaths in the CrAg-positive group seemed to be due to cryptococcal meningitis. This study suggests that even short-course intensive fluconazole could reduce the mortality of patients with asymptomatic cryptococcal antigenemia. Further studies are needed to confirm if this dose is both optimal for patient survival and feasible for wide implementation in resource-poor settings where mortality of cryptococcal disease is highest.


Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort.
As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8 years. Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.


Relationships Between Quality of Life in the Psychological Domain, Acceptance of Illness, and Healthcare Services in Patients with Asthma.
Asthma patients should be considered not only in terms of the medical aspects, but also the nonmedical issues associated with the psychological domain, since these are factors that can significantly improve patients' health state, quality of life, and illness acceptance, and can contribute to the reduction of healthcare utilization. The purpose of this study was to assess the acceptance of illness among asthma patients and their quality of life in the psychological domain, as well as to identify factors that influence illness acceptance and quality of life in the psychological domain. We examined 172 patients with asthma (median age: 58; range: 18-89 years) recruited from two pulmonology wards. We demonstrate that the patients with low levels of illness acceptance and a high healthcare service index had low quality of life in the mental domain. Older age; being separated, divorced, or widowed; and having BMI > 25, all significantly affect the levels of quality of life and illness acceptance. In conclusion, measurements of health-related quality of life and illness acceptance are useful for estimating the impact and progression of asthma. These results confirm that psychological functioning should be taken into account alongside the somatic state.


Systemic sclerosis induced by CNS stimulants for ADHD: A case series and review of the literature.
Methylphenidate (Ritalin) is a CNS stimulant, and is a common treatment for children and adults with ADHD. It has been associated with Raynaud's phenomenon (RP) but not with Systemic Sclerosis (SSc). We report a case series of patients pointing out the connection between Methylphenidate and SSc. We identified three patients in a single Rheumatology clinic in Israel, who developed SSc following treatment with CNS stimulants for ADHD. All three cases had Raynaud's phenomenon, skin changes, pathological capillaroscopy and positive ANA. Symptoms appeared and worsened over months following the use of methylphenidate and subsided after its cessation. This is the first report in the literature of a causative relation between methylphenidate and the development of SSc, a serious, life-threatening condition. Patients treated with CNS stimulants should be followed closely for side-effects such as RP and skin changes.


Predictive value of a novel Asian lung cancer screening nomogram based on artificial intelligence and epidemiological characteristics.
To develop and validate a risk prediction nomogram based on a deep learning convolutional neural networks (CNN) model and epidemiological characteristics for lung cancer screening in patients with small pulmonary nodules (SPN). This study included three data sets. First, a CNN model was developed and tested on data set 1. Then, a hybrid prediction model was developed on data set 2 by multivariable binary logistic regression analysis. We combined the CNN model score and the selected epidemiological risk factors, and a risk prediction nomogram was presented. An independent multicenter cohort was used for model external validation. The performance of the nomogram was assessed with respect to its calibration and discrimination. The final hybrid model included the CNN model score and the screened risk factors included age, gender, smoking status and family history of cancer. The nomogram showed good discrimination and calibration with an area under the curve (AUC) of 91.6% (95% CI: 89.4%-93.5%), compare with the CNN model, the improvement was significance. The performance of the nomogram still showed good discrimination and good calibration in the multicenter validation cohort, with an AUC of 88.3% (95% CI: 83.1%-92.3%). Our study showed that epidemiological characteristics should be considered in lung cancer screening, which can significantly improve the efficiency of the artificial intelligence (AI) model alone. We combined the CNN model score with Asian lung cancer epidemiological characteristics to develop a new nomogram to facilitate and accurately perform individualized lung cancer screening, especially for Asians.


Fish oil omega-3 Fatty Acids Alleviate Postoperative delirium-like Behavior in aged mice by Attenuating Neuroinflammation and Oxidative Stress.
Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.


Optical coherence tomography characteristics of choroidal metastasis.
To report 4 patients (7 eyes) with choroidal metastasis (primary: breast [2], lung [1], and unknown [1]) visualized with optical coherence tomography (OCT). Retrospective case series. Four patients (7 eyes) with choroidal metastasis participated in the study. Clinical examination, ultrasonography, fluorescein angiography, and OCT were performed in all cases. Optical coherence tomography characteristics. Three patients suffered a gradual onset of blurred vision in both eyes. The fourth presented a unilateral decrease in visual acuity. Bilateral choroidal lesions with various degrees of exudative retinal detachment (RD) were present in 3 of our 4 patients, and there was 1 case of a unilateral unifocal choroidal lesion. Optical coherence tomography revealed anterior displacement of the photoreceptor layer by subretinal fluid (hyporeflective space) overlying a hyperreflective thickened retinal pigment epithelium-choriocapillaris complex. Subretinal deposits with several degrees of hyperreflectivity were seen, as well as loss of normal retinal architecture with intraretinal splitting, identified as regions of low reflectance within the neurosensory retina. After chemotherapy, OCT demonstrated improvement of the serous RD and reduction of the lesion's size with recovery of the normal retinal architecture. Optical coherence tomography in patients with choroidal metastasis allows evaluation of secondary retinal-retinal pigment epithelial changes. In addition, the technique is useful in the follow-up of lesions after treatment. However, some limitations result from the choroidal location of the metastasis. Further studies with clinicopathological correlation are needed to confirm our observations.


Dystrophic xanthomatosis in primary CD30-positive cutaneous T-cell lymphoma. Report of two cases and review of the literature.
The development of xanthomatous changes in lesions of primary cutaneous T-cell lymphomas (CTCL) is a rare event. It is usually observed in regressing skin tumours or plaques spontaneously or after a specific treatment. The pathogenetic mechanisms implicated in these changes are poorly understood. We are reporting 2 cases of extensive dystrophic xanthomatous changes, developing in regressing lesions of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Previously reported cases of primary CTCL developing secondary (dystrophic) xanthomata are reviewed.


Prevalence and optical coherence tomography analyses of outer retinal tubulations in Chinese population with inherited retinal diseases.
To investigate the prevalence of outer retinal tubulation (ORT) and its correlations with optical coherence tomography (OCT) parameters in Chinese population with inherited retinal diseases (IRDs). This retrospective study enrolled consecutive patients identified with IRDs and referred for genetic testing between February 2016 and April 2021. Clinical characteristics from medical records and features of cross-sectional B-scans were reviewed and analysed. The associations of patient-specific and ocular features with the presence of ORT were evaluated using univariate and multivariate analyses. Two hundred and three patients (401 eyes) with a mean age of 49.7 ± 16.7 years were enrolled. ORT was observed in 41 eyes (10.2%), including 26 of 28 eyes (92.9%) with Bietti crystalline corneoretinal dystrophy (BCD), 14 of 338 eyes (4.1%) with retinitis pigmentosa (RP), and 1 of 26 eyes (3.8%) in eyes with cone-rod dystrophy. Eyes with ORT showed significantly worse visual acuity than those without ORT (P = 0.002). Multivariate analysis indicated that the presence of ORT was positively correlated with choroidal atrophy and inner nuclear layer (INL) cysts (P < 0.01). ORTs were detected more frequently in eyes with BCD than RP (P = 0.024), most of which located exclusively within the extrafoveal area. Large choroidal vessels were detected underneath the corresponding ORTs in both patients with BCD and RP. The prevalence of ORT varies among different IRDs phenotypes, with the highest prevalence in BCD. The presence of choroidal atrophy and INL cysts may be associated with an increased risk of ORT formation in patients with IRD.


Deletion of a xenobiotic metabolizing gene in mice affects folate metabolism.
The mouse arylamine N-acetyltransferase 2 (Nat2) and its homologue (NAT1) in humans are known to detoxify xenobiotic arylamines and are also thought to play a role in endogenous metabolism. Human NAT1 is highly over-expressed in estrogen receptor positive breast tumours and is implicated in susceptibility to neural tube defects. In vitro assays have suggested an endogenous role for human NAT1 in folate metabolism, but in vivo evidence to support this hypothesis has been lacking. Mouse Nat2 provides a good model to study human NAT1 as it shows similar expression profiles and substrate specificities. We have generated transgenic mice lacking a functional Nat2 gene and compared the urinary levels of acetylated folate metabolite para-aminobenzoylglutamate in Nat2 knockout and Nat2 wild-type mice. These results support an in vivo role for mouse Nat2/human NAT1 in folate metabolism. In addition, effects of the Nat2 deletion on sex ratios and neural tube development are described.


Association between vitamin D status and physical performance in COVID-19 survivors: Results from the Gemelli against COVID-19 post-acute care project.
To determine the prevalence and associated factors of vitamin D deficiency in COVID-19 survivors and the relationship between vitamin D status and physical performance. Vitamin D status was assessed in a sample of patients who had recovered from COVID-19 and were admitted to a post-acute outpatient service at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participants were offered comprehensive medical assessment, including physical performance and muscle strength tests. Self-rated health was assessed. Vitamin D deficiency was defined as a serum concentration of 25-OH vitamin D < 20 ng/mL. Mean age of 681 participants was 53.4 ± 15.2 years and 49% were women. Vitamin D deficiency was detected in 35.6% of the whole study population, and in 40.2% of those 65 and older. Vitamin D deficiency was associated with diabetes, higher body mass index, and COVID-19 severity, and showed a seasonal pattern with a peak in autumn/winter. Participants with vitamin D deficiency performed poorer on the six-minute walking test, with the lowest performance observed in those 65 and older. No significant associations with any other parameters were found. Our findings indicate that vitamin D deficiency is frequent in COVID-19 survivors, especially in older adults. Low vitamin D levels are associated with poor physical performance, in particular in old age.


Does oral zinc aid the healing of chronic leg ulcers? A systematic literature review.
To determine whether oral zinc sulfate is an effective treatment for promoting healing of venous or arterial leg ulcers. The search strategy of the Cochrane Wounds Group was used. This includes searches of electronic databases, conference proceedings, relevant bibliographies, and hand searching of journals. Studies were included if they were randomized controlled trials of oral zinc sulfate in the treatment of chronic venous or arterial ulcers with objective measures of healing. Six of the 10 studies initially identified were included in the review. The trial method, participants, interventions, outcomes, baseline comparability, adequate reporting of withdrawals, and blinding of assessment were extracted by 2 reviewers independently. No trial showed a statistically significant benefit of zinc sulfate for healing leg ulcers. There is limited evidence to suggest that zinc might increase healing in individuals with a low serum zinc level, but more evidence is needed. There is no evidence of benefit from the general use of zinc sulfate in patients with chronic leg ulcers. There is a need for further research to see if oral zinc sulfate is beneficial in the treatment of patients with leg ulcers who have a low serum zinc level. If it is demonstrated to be beneficial, further trials are required to establish dose and duration of treatment.


A review of infliximab use in ulcerative colitis.
Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-alpha found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohn's disease (CD), with documented success. Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC. The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment. A search of MEDLINE was conducted (1950-November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized. Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey. Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximab's impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.


[Synthesis and virostatic activity of adamantan-1-carbonic acid amidines (author's transl)].
33 different adamntyl amidines containing four different structural types were synthesized and checked for virostatic activity. The activity of compounds of type II seems to originate in their ability to form H-bonds. The strength of antiviral activity is at least partly determined by the electronic effects of substituents at the benzene ring.


[Hypercalcemia and osteoclast activating factor (OAF) associated with acute lymphoblastic leukemia (author's transl)].
The occurence of hypercalcemia appears to be unusual in leukemia. The mechanisms are numerous: secretion of PTH of PTH like substance, prostaglandin E2 or vitamin D like sterols. The reported case is one of lymphoblastic acute leukemia and hypercalcemia associated with osteoclast activating factor secreted by leukemic cells. In this patient the serum levels calcium closely paralleled the course of acute leukemia.


Small bowel intussusception: an unusual complication of retroperitoneal lymph node dissection.
Modified bilateral retroperitoneal lymph node dissection is used widely in the staging and treatment of patients with nonseminomatous germ cell testis tumors. Complications are uncommon and include vascular injury, infertility and small bowel obstruction from fibrous adhesions. Small bowel intussusception following retroperitoneal lymph node dissection has not been reported previously. We report 2 cases of small bowel intussusception after retroperitoneal lymph node dissection, and discuss the etiology and possible preventive measures.


[Reaction of cells in the anterior lobe of the rat pituitary after acute cooling].
The anterior hypophysis (AH) of rat exposed to total cooling at --10 degrees C for 6 min was studied histologically and autoradiographically. 3, 6, 12, 18, and 24 hours after the exposure the diurnal cycle of modifications of the functional state of the AH secretory cells, the number of mitoses and of the labeled DNA-synthesizing cells was traced. In 12 hours a considerable activation of the thyrotrops and a doubling of mitoses occurred; there was no change of the labeled cells index for twenty four hours. The data obtained showed that stress reaction to cold was characterized by the intensification of the thyrotropic function and an acceleration of mitotic process in the AH cells.


The electroencephalographic and psychological effects of imipramine in depressed inpatients.
Ten patients with psychotic depression were assessed on a battery of clinical, EEG, psychological, and biochemical measures during treatment with imipramine (150 mg/day). Significant changes occurred in the scores on self-rated and observer-rated depression scales and on an observer-rated side effect scale. Significant changes also occurred in the EEG evoked response, but the effects on spontaneous activity were minimal. The psychological measures revealed an improvement in performance as treatment progressed. The clinical significance of the changes observed was assessed with reference to their correlations with the clinical rating scores and with the plasma concentrations of imipramine and desmethylimipramine, and the changes observed following the administration of imipramine to non-depressed normal subjects. Changes in evoked EEG activity seemed on balance to be direct central effects of imipramine, whereas changes in psychological performance appeared to be secondary to clinical change.


Co-requirement of cyclic AMP- and calcium-dependent protein kinases for transcriptional activation of cholecystokinin gene by protein hydrolysates.
Little is known about the mechanisms by which protein-derived nutrients regulate hormone gene expression in the intestine. We have previously reported that protein hydrolysates (i.e. peptones), which are representative of the protein fraction in the lumen, increased cholecystokinin (CCK) gene transcription in the STC-1 enteroendocrine cell line. In the present work, we examined the intracellular events evoked by peptones to stimulate CCK gene transcription. In STC-1 cells, peptones stimulated cyclic AMP production and protein kinase A (PKA) activity. This was associated with a nuclear translocation of the PKA catalytic subunit and with a PKA-dependent phosphorylation of the CRE-binding protein (CREB) at Ser(133). Using transient transfection experiments and reporter luciferase assays, we show that peptone-stimulated transcriptional activity of the CCK gene promoter was significantly decreased when the PKA pathway was inhibited. Furthermore, the intracellular calcium chelator 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra(acetoxymethyl)ester completely inhibited peptone-induced stimulation of the CCK gene promoter activity, phosphorylation of CREB, and PKA activity. Peptones increased, in a calcium-dependent manner, the phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and the MEK inhibitor PD98059 decreased the peptone-induced stimulation of CCK gene promoter activity. This stimulation was also reduced by 30% in the presence of the calcium/calmodulin-dependent protein kinase (CaMK) inhibitor KN-93. Total inhibition was obtained when the PKA, ERK, and CaMK pathways were simultaneously blocked with appropriate inhibitors to these pathways. These results demonstrate the simultaneous involvement of cAMP- and calcium-dependent protein kinases in the stimulation of intestinal CCK gene transcription by protein-derived nutrients.


Texture analysis of CT images in predicting malignancy risk of gastrointestinal stromal tumours.
To explore the role of texture analysis of computed tomography (CT) images in predicting the malignancy risk of gastrointestinal stromal tumours (GISTs). Seventy-eight patients with histopathologically confirmed GISTs underwent preoperative CT. Texture analysis was performed on unenhanced and contrast-enhanced CT images, respectively. Fourteen CT texture parameters were obtained and compared among GISTs at different malignancy risks with one-way analysis of variance or independent-samples Kruskal-Wallis test. Correlations between CT texture parameters and malignancy risk were analysed with Spearman's correlation test. Diagnostic performance of CT texture parameters in differentiating GISTs at low/very low malignancy risk was tested with receiver operating characteristic (ROC) analysis. Three parameters on unenhanced images (r=-0.268-0.506), four parameters on arterial phase (r=-0.365-0.508), and six parameters on venous phase (r=-0.343-0.481) imaging correlated significantly with malignancy risk of GISTs, respectively (all p<0.05). For identifying GISTs at low/very low malignancy risk, three parameters on unenhanced images (area under ROC curve [AUC], 0.676-0.802), four parameters on arterial phase (AUC, 0.637-0.811), and six parameters on venous phase (AUC, 0.636-0.791) imaging showed significant diagnostic performance, respectively (all p<0.05), especially maximum frequency on both unenhanced and contrast-enhanced images (AUC, 0.791-0.811). Texture analysis of CT images holds great potential to predict the malignancy risk of GISTs preoperatively.


A Beginner's Guide to the COBRA Toolbox.
COBRA toolbox is one of the most popular tools for systems biology analyses using genome-scale metabolic reconstructions. The toolbox permits the use of many constraint-based analytical methods for examining characteristics of metabolism in the biosystems ranging in complexity from single cells to microbial communities and ultimately multicellular organisms. The toolbox has a number of different variants that can be used depending on a user's choice of programming language. Here, I provide a basic tutorial for beginners that plan to use the original MATLAB version of the toolbox.


Catch-up growth is a better indicator of undernutrition than thresholds for stunting.
Stunting (height-for-age < -2 sd) is one of the forms of undernutrition and is frequent among children of low- and middle-income countries. But stunting perse is not a synonym of undernutrition. We investigated association between body height and indicators of energetic undernutrition at three critical thresholds for thinness used in public health: (1) BMI SDS < -2; (2) mid-upper arm circumference divided by height (MUAC (mm) × 10/height (cm) < 1·36) and (3) mean skinfold thickness (SF) < 7 mm and to question the reliability of thresholds as indicators of undernutrition. Cross-sectional study; breakpoint analysis. Rural and urban regions of Indonesia and Guatemala - different socio-economic status (SES). 1716 Indonesian children (6·0-13·2 years) and 3838 Guatemalan children (4·0-18·9 years) with up to 50 % stunted children. When separating the regression of BMI, MUAC or SF, on height into distinguishable segments (breakpoint analysis), we failed to detect relevant associations between height, and BMI, MUAC or SF, even in the thinnest and shortest children. For BMI and SF, the breakpoint analysis either failed to reach statistical significance or distinguished at breakpoints above critical thresholds. For MUAC, the breakpoint analysis yielded negative associations between MUAC/h and height in thin individuals. Only in high SES Guatemalan children, SF and height appeared mildly associated with R2 = 0·017. Currently used lower thresholds of height-for-age (stunting) do not show relevant associations with anthropometric indicators of energetic undernutrition. We recommend using the catch-up growth spurt during early re-feeding instead as immediate and sensitive indicator of past undernourishment. We discuss the primacy of education and social-economic-political-emotional circumstances as responsible factors for stunting.


Demonstration of accessory pathway interaction by computerized mapping in preexcitation syndrome.
While interaction between the normal conduction system and an accessory pathway (AP) has been reported, interaction between two APs has not been well documented. With the assistance of computerized mapping techniques, we recently operated on a patient with two APs. One of these two APs had slow anterograde conduction velocity and was concealed during sinus rhythm and atrial pacing. Intraoperative computerized mapping studies revealed that the interaction between the APs was responsible for the anterograde conduction block of the slow AP during sinus rhythm and atrial pacing. This is the first direct demonstration of inhibition of conduction of one AP by the other AP in a patient with preexcitation syndrome.


Antimicrobial susceptibility and prevalence of resistance genes in Bacteroides fragilis isolated from blood culture bottles in two tertiary care hospitals in Japan.
The in vitro susceptibilities of Bacteroides fragilis to antimicrobial agents, especially to carbapenem, are a major concern in the treatment of patients with bloodstream infections. In this study, 50 isolates of B. fragilis were obtained from positive blood bottles from 2014 to 2019 in Saitama, Japan. Their susceptibility to ampicillin/sulbactam was reduced to 70.0% compared with a previous report, whereas they were still sufficiently susceptible to piperacillin/tazobactam (94.0%). Five cfiA-positive isolates (5/50, 10.0%) were identified that were resistant to doripenem and meropenem, and two of them carried an insertion sequence located upstream of the cfiA-coding region. In particular, imipenem should be considered as a first-line carbapenem for the empirical treatment of B. fragilis infection because only insertion sequence and cfiA double-positive strains showed resistance to imipenem. Thirty-six percent of the isolates had a reduced minimum inhibitory concentration for moxifloxacin. In addition, metronidazole should still be considered as an active agent for B. fragilis because all isolates were susceptible to this antibiotic and the prevalence of the nim gene was low in Japan.


Small deletion in v-src SH3 domain of a transformation defective mutant of Rous sarcoma virus restores wild type transforming properties.
RSV mutant virus PA101T was obtained while assaying the tumorigenicity of parental PA101 virus in chickens. PA101 is a transformation defective mutant of RSV which has a low src kinase activity. However, PA101 retained a temperature-sensitive ability to induce sustained proliferation of neuroretina cells. PA101T appeared as a wild-type phenotype revertant of PA101. Molecular cloning and sequencing of PA101T showed that this reversion is due to additional mutations in PA101 src gene. These mutations are a deletion eliminating three amino acids in the N-terminal region of SH3 domain and mutation of Ala 426 to Val. Analysis of the properties of chimeric src genes associating either half of PA101T with the complementary regions of PA101 or wild-type virus showed that the N-terminal moiety of PA101T src, which contains the deletion, confers wild-type transforming properties, whereas its C-terminal moiety, which contains single amino acid mutation, confers a partially temperature-sensitive phenotype. These results are consistent with other reports showing that mutations or deletions in this region of SH3 activate the transforming potential of c-src. They support the hypothesis that the N-terminal region of SH3 interacts with a cellular negative regulator of src activity.