Risk of Retinal Artery Occlusion in Patients with Migraine.
We sought to determine if migraine is associated with increased risk of retinal artery occlusion (RAO). Retrospective cohort study. We reviewed a large insurance claims database for patients with migraine and matched control subjects without migraine between 2007 and 2016. Cox proportional hazard regression models were used to investigate the association between migraine and risk of all RAO, central RAO (CRAO), branch RAO (BRAO), and "other" RAO, which includes transient and partial RAO. Primary outcome measures included the incidence of all RAO, including CRAO, BRAO, and other RAO, after first migraine diagnosis. There were 418,965 patients with migraine who met the study criteria and were included in the analysis with the appropriate matched control subjects. Among the 418,965 patients with migraine, 1060 (0.25%) were subsequently diagnosed with RAO, whereas only 335 (0.08%) of the patients without migraine were diagnosed with RAO. The hazard ratio (HR) for incident all RAO in patients with migraine compared with those without migraine was 3.48 (95% confidence interval [CI] 3.07-3.94; P < .0001). This association was consistent across all types of RAO, including CRAO (HR 1.62 [95% CI 1.15-2.28]; P = .004), BRAO (HR 2.09 [95% CI 1.60-2.72]; P < .001), and other types of RAO (HR 4.61 [95% CI 3.94-5.38]; P < .001). Patients with migraine with aura had a higher risk for incident RAO compared with those with migraine without aura (HR 1.58 [95% CI 1.40-1.79]; P < .001). This association was consistent for BRAO (HR 1.43 [95% CI 1.04-1.97]; P < .03) and other types of RAO (HR 1.67 [95% CI 1.45-1.91]; P < .001) but was not statistically significant for CRAO (HR 1.18 [95% CI 0.75-1.87]; P = .475). Significant risk factors for this association included increased age, male sex, acute coronary syndrome, valvular disease, carotid disease, hyperlipidemia, hypertension, retinal vasculitis or inflammation, and systemic lupus erythematosus. Migraine is associated with increased risk of all types of RAO and migraine with aura is associated with increased risk of RAO compared with migraine without aura.


Renal angiomyolipoma; polycystic kidney, and renal cell carcinoma in patient with tuberous sclerosis.
A patient with tuberous sclerosis presented with renal failure secondary to bilateral angiomyolipoma. The angiomyolipoma was associated with polycystic disease and a foci of renal cell carcinoma. This unusual combination has not been reported previously, although each entity has been described separately in tuberous sclerosis.


Signal of induction of recA protein in E. coli.
The nature of the signal(s) responsible for the induction of the SOS functions in E. coli was investigated in dnaA and dnaC mutants, in which recA protein was induced by UV irradiation under conditions where no DNA replication could occur. This induction was dependent upon an active excision-repair system, since it was abolished in a dnaC uvrB double mutant at non-permissive temperature. In such a case, the addition of bleomycin, an agent known to produce single-strand breaks into DNA, was able to restore the induction of the recA protein.


Prevalence and prognostic impact of tricuspid regurgitation in patients with cardiac implantable electronic devices: From the national echocardiography database of Australia.
We sought to analyse the distribution of TR severity and survival in a large cohort of adults with CIED leads. The distribution of TR severity was analysed in 18,797 adults (mean age 73.8+/-13.9, 63.3% men) with CIED leads undergoing echocardiography across 25 centres. Survival status and cause of death were linked and the relationship between TR severity and mortality during 2.6 (interquartile range 1.1-4.6) years follow-up examined. Data from 439,558 individuals (mean age 62.1 ±17.8 years, 51.5% men) without a CIED were subsequently incorporated in a pooled cohort analysis. Overall, 8,824/18,797 individuals (47%) with a CIED had no/trivial TR; 5,490 (29.2%) mild TR; 3,068 (16.3%) moderate TR; and 1,415 (7.5%) severe TR. Moderate or greater TR was independently associated with age, female sex, atrial fibrillation and significant left heart disease (p<0.001 for all). 8,868 individuals (47.2%) died from any cause (43.2% from cardiovascular causes). Individuals with moderate or severe TR had a 1.6 to 2.5-fold increased risk of all-cause mortality in adjusted models, compared to those with no TR (p<0.001 for both). In the pooled cohort analysis, CIEDs were associated with a near 2-fold (95% CI 1.81-1.99; p<0.001) increased probability of moderate or greater TR, on adjusted basis. However, the mortality associated with moderate or greater TR did not differ significantly with respect to the presence or absence of a device lead. Moderate or greater TR is more prevalent in those with CIED's, even in adjusted models, and was independently associated with incremental risks for all-cause and cardiovascular mortality.


Enhanced subunit interactions with gemcitabine-5'-diphosphate inhibit ribonucleotide reductases.
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms. The class I RNRs are composed of two subunits, alpha and beta, with proposed quaternary structures of alpha2beta2, alpha6beta2, or alpha6beta6, depending on the organism. The alpha subunits bind the nucleoside diphosphate substrates and the dNTP/ATP allosteric effectors that govern specificity and turnover. The beta2 subunit houses the diferric Y* (1 radical per beta2) cofactor that is required to initiate nucleotide reduction. 2',2'-difluoro-2'-deoxycytidine (F2C) is presently used clinically in a variety of cancer treatments and the 5'-diphosphorylated F2C (F2CDP) is a potent inhibitor of RNRs. The studies with [1'-(3)H]-F2CDP and [5-(3)H]-F2CDP have established that F2CDP is a substoichiometric mechanism based inhibitor (0.5 eq F2CDP/alpha) of both the Escherichia coli and the human RNRs in the presence of reductant. Inactivation is caused by covalent labeling of RNR by the sugar of F2CDP (0.5 eq/alpha) and is accompanied by release of 0.5 eq cytosine/alpha. Inactivation also results in loss of 40% of beta2 activity. Studies using size exclusion chromatography reveal that in the E. coli RNR, an alpha2beta2 tight complex is generated subsequent to enzyme inactivation by F2CDP, whereas in the human RNR, an alpha6beta6 tight complex is generated. Isolation of these complexes establishes that the weak interactions of the subunits in the absence of nucleotides are substantially increased in the presence of F2CDP and ATP. This information and the proposed asymmetry between the interactions of alphanbetan provide an explanation for complete inactivation of RNR with substoichiometric amounts of F2CDP.


Optimizing control of simulated moving beds--experimental implementation.
The operation of simulated moving beds (SMBs) at their optimal operating conditions is difficult and not robust. Therefore, it is common practice to operate SMB units far from their economic optimum in order to tolerate uncertainties in the system and minimize the effect of disturbances. Recently, we have proposed an on-line optimization based SMB control scheme that allows to exploit the full economic potential of SMB technology. The goal of this work is two-fold. Firstly, to experimentally evaluate and demonstrate the capability of the controller to optimize and operate the SMB units, thus delivering the products with maximum productivity and minimum solvent consumption. Secondly, to show the suitability of the controller even using a minimum of system information, thus making the detailed isotherm measurements redundant and saving time in the separation design phase. This paper reports and discusses the first experimental implementation of the control concept on a high purity separation of nucleosides (uridine, guanosine) with an eight-column four-section SMB where the species to be separated are retained on the source 30RPC stationary phase according to a linear isotherm.


Anhedonia and Delay Discounting: Differing Patterns of Brain-Behavior Relationships in Healthy Control Participants Versus Individuals With Posttraumatic Stress Disorder.
Anhedonia may contribute to individual differences in delay discounting (DD). In prior work, we found that higher anhedonia was associated with shallower DD in healthy control (HC) participants but steeper DD in individuals with posttraumatic stress disorder (PTSD). In this study, we aimed to directly compare the relationship between anhedonia and DD across groups and to identify functional brain correlates of this interaction. Participants (HC group: n = 23, DSM-5 PTSD group: n = 23) completed a questionnaire assessing anhedonia (Snaith-Hamilton Pleasure Scale [SHAPS]), task-based functional magnetic resonance imaging of decision making including DD, and resting-state functional magnetic resonance imaging. Task-based activity and resting-state functional connectivity were evaluated in reward-related regions that have also been implicated in PTSD (nucleus accumbens [NAcc], right anterior insula). Higher SHAPS scores were associated with steeper DD in PTSD, but there was no relationship between DD and SHAPS in the HC group. There was a significant group-by-SHAPS interaction for NAcc activity, t31 = 2.92, p = .007: Greater NAcc activity when immediate rewards were chosen was associated with higher SHAPS in the PTSD group but lower SHAPS in the HC group. In resting-state functional connectivity, there was a group-by-SHAPS interaction between the NAcc seed and right parietal and frontal pole clusters. These results extend prior findings that anhedonia is associated with steeper DD in PTSD and demonstrate that this behavioral finding occurs in the context of NAcc hyperactivity to immediate rewards and hyperconnectivity in anhedonic individuals with PTSD.


Characterization of microsatellite markers for Moricandia moricandioides (Brassicaceae) and related species.
Polymorphic microsatellite markers were developed to study population structure and mating patterns of the monocarpic herb Moricandia moricandioides (Brassicaceae). Illumina MiSeq sequencing was used to develop a panel of 15 polymorphic microsatellite markers that were tested across 77 individuals from three populations on the Iberian Peninsula. All markers were polymorphic in at least two studied populations, and the number of alleles ranged from one to 11 per locus. The levels of observed and expected heterozygosity ranged from 0.000 to 1.000 and from 0.153 to 0.865, respectively. Nine and 11 loci were successfully amplified in the congeneric species M. arvensis and M. foetida, respectively. The 15 microsatellite markers will be useful for population genetic studies of the genus Moricandia. These markers will serve as a useful tool for exploring population structure and mating patterns of M. moricandioides.


Excision repair of UV damage in human fibroblasts reversibly permeabilized by lysolecithin.
We have examined nucleotide excision repair synthesis in confluent human diploid fibroblasts permeabilized with lysolecithin. Following a UV dose of 12 J/m2, maximal incorporation of [alpha 35S]dNTPs occurred at a lysolecithin concentration (approximately 80 micrograms/ml) where slightly more than 90% of the cells were initially permeable to trypan blue. However, autoradiography of cells, permeabilized at this lysolecithin concentration, demonstrated that only about 20% of the total cell population incorporated significant levels of 35S into DNA. This result presumably reflected the fact that approximately 20% of the total cell population remained permeable for much longer periods of time (up to 2 h) than the remaining cell population (less than 20 min). The incorporation of dNTPs by UV-irradiated, permeabilized cells appeared to be bona fide excision repair synthesis since: (1) Incorporation was completely absent in unirradiated, permeabilized cells and in irradiated, permeabilized repair-deficient cells. (2) Nucleotides incorporated in the presence of BrdUTP were associated with normal density DNA. (3) The apparent Km for all 4 dNTPs was 50-100 nM, in agreement with past reports on human fibroblasts irreversibly permeabilized by cell lysis. (4) DNA associated with the newly incorporated dNTPs underwent ligation and rearrangements in chromatin structure analogous to what is observed in intact human cells. Repair incorporation of dNTPs was rapid and linear during the first 2 h after UV irradiation and permeabilization. After this time, incorporation ceased or continued at a much slower rate. Cell viability experiments and autoradiography demonstrated that the cells permeabilized to [3H]dNTPs were capable of carrying out DNA replication and cell division. Thus, confluent human diploid fibroblasts can be reversibly permeabilized to labeled dNTPs by lysolecithin for the study of excision repair following physiologic doses of UV radiation. However, under these conditions, only a fraction of the cells remain permeable for an extended period of time.


Multi-wall carbon nanotube-polyaniline biosensor based on lectin-carbohydrate affinity for ultrasensitive detection of Con A.
In this paper, a novel method for detecting concanavalin A (Con A) was developed based on lectin-carbohydrate biospecific interactions. Multi-wall carbon nanotube-polyaniline (MWNT-PANI) nanocomposites, synthesized by in situ polymerization, were chosen to immobilize d-glucose through the Schiff-base reaction. The immobilized D-glucose showed high binding sensitivity and excellent selectivity to its target lectin, Con A. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), transmission electron microscopy (TEM) and atomic force microscopy (AFM) were applied to characterize the assembly process of the modified electrode. Due to the high affinity of Con A for D-glucose and high stability of the propounded sensing platform, the fabricated biosensor achieved ultrasensitive detection of Con A with good sensitivity, acceptable reproducibility and stability. The changes of response current were proportional to the Con A concentrations from 3.3 pM to 9.3 nM, with a detection limit of 1.0 pM. Therefore, the combination of MWNT-PANI nanocomposites and the special binding force between lectin and carbohydrate provides an efficient and promising platform for the fabrication of bioelectrochemical devices.


Through the eyes of a hunter: assessing perception and exclusion performance in ground-hornbills.
Logical inference, once strictly associated with spoken language, is now reported in some non-human animals. One aspect of logical inference, reasoning by exclusion, has been traditionally explored through the use of the cups task (cup A and cup B, if not cup A, then exclude cup A and select cup B). However, to fully understand the factors that drove the evolution of logical processes in animals, this latter paradigm needs to cover a taxonomically broader spectrum of species. In this study, we aimed to test the capacity of Southern ground-hornbills (Bucorvus leadbeateri) to show exclusion performance in a two-way object-choice task. First, we determined whether subjects could perceive and choose correctly between two containers (one rewarded, one unrewarded) using visual or acoustic cues (sensory phase). If successful, individuals were then presented with three experimental conditions (test phase): Full information (content of both cups revealed), Exclusion (content of the empty cup revealed), and Control (no content revealed). During the sensory phase, ground-hornbills succeeded in choosing the rewarded container only in the visual modality. Birds were able to select the rewarded container more than would be expected by chance in the Full information condition, but their performances were equal to chance in the Control condition. The without-learning performance of two individuals within the Exclusion condition indicates that this task is not trivial, which invites further investigation on this species' capacity to represent the dependent relationship between the cups (true logical inference).


[Assay of sex hormone-binding globulin (SHBG) in human serum. Comparative measurements using three methods].
Determination of sex-hormone-binding-globulin was performed by three methods: binding, electroimmunodiffusion and DELFIA methods. Results of normal and pathological values correlated well with the three techniques.


GRIM-19 expression is a potent prognostic marker in colorectal cancer.
Retinoid-interferon-induced mortality-19 (GRIM-19), a recently discovered cell death regulatory gene, may function as a tumor suppressor in many human malignancies. However, the expression of GRIM-19 in and its prognostic value for patients with colorectal cancer (CRC) have not been well investigated to date. Here, GRIM-19 expression was measured immunohistochemically in 94 colon samples and by quantitative real-time reverse transcriptase polymerase chain reaction in 15 paired CRC tissues and adjacent normal tissues. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Our results showed that GRIM-19 mRNA and protein levels in adenoma tissues were similar to those in adjacent normal tissues. However, GRIM-19 expression was severely depressed in carcinomas compared to matched normal tissues (P = .000). Additionally, we found GRIM-19 to be located in both the cytoplasm and nucleus in normal tissues but only in the cytoplasm in CRC tissues. Alteration in GRIM-19 expression occurs early in the pathogenesis of CRC; moreover, low GRIM-19 expression was associated with poor tumor differentiation (P = .013), the presence of lymph nodes (P = .000), metastasis to other organs (P = .045) and vascular invasion (P = .010). During a mean period of 40 months follow-up, patients without GRIM-19 had a statistically significantly lower rate of recurrence/metastasis (P < .05) and a shorter overall survival time (P < .01) than the patients with GRIM-19 expression. Taken together, GRIM-19 expression is closely associated with CRC progression and might be a very promising prognostic biomarker for CRC patients.


Motor resonance and linguistic focus.
Previous studies have demonstrated that verbal descriptions of actions activate compatible motor responses (Glenberg & Kaschak, 2002; Zwaan & Taylor, 2006). The present study replicates previous findings showing that, within a sentence, such activation is localized on the verb that denotes the action. Moreover, motor resonance is found to yield to linguistic focus. If a postverbal adverb maintains focus on a matching action ("slowly" or "quickly"), motor resonance occurs, but if the adverb shifts the focus to the agent (e.g., "obediently" or "eagerly"), a cessation of motor resonance ensues. These findings are discussed within the context of theories of motor resonance, action understanding, mental simulation, and linguistic focus.


Psychometric validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24).
A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of the quality of life (QoL) of patients with endometrial cancer. Two hundred and sixty-eight women with endometrial cancer were recruited in different phases of treatment: after pelvic surgery (Group 1); during adjuvant chemotherapy and/or radiotherapy (Group 2); after completion of treatment (Group 3). Patients completed the EORTC QLQ-C30, the endometrial cancer module and a short debriefing questionnaire. Multi-trait scaling analyses confirmed the hypothesised scale structure of the QLQ-EN24. Internal consistency reliability was good with Cronbach's alpha coefficients ranging from 0.74 to 0.86 (lymphoedema 0.80, urological symptoms 0.75, gastrointestinal symptoms 0.74, body image problems 0.86 and sexual/vaginal problems 0.86). Convergent and discriminant validity did not show any scaling errors for the subscales. The QLQ-EN24 module discriminated well between clinically different groups of patients. All items exhibited a high completion rate with less than 2% missing values except for the sexuality items (19%). The validation study supports the reliability, the convergent and divergent validity of the EORTC QLQ-EN24. This newly developed QLQ-EN24 module is a useful instrument for the assessment of the QoL in patients treated for endometrial cancer in clinical trials.


Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.
Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease.


Effect of dobutamine stress on left ventricular filling in ischemic dilated cardiomyopathy: pathophysiology and prognostic implications.
The purpose of this research was to study the effect of dobutamine on left ventricular (LV) filling in ischemic cardiomyopathy (ICM) and to determine whether restrictive filling pattern (RFP) at peak stress has prognostic value. The prognostic value of RFP at peak stress in ICM is unknown. A total of 69 patients with ICM were studied by Doppler echocardiography at rest and stress; RFP was defined as transmitral E:A ratio > or =1.0, isovolumic relaxation time (IVRT) <80 ms, and E-wave deceleration time (EDT) <120 ms. A total of 42 of 69 had RFP at rest, which reverted to non-RFP at stress in 24 (EA), but persisted in 18 (EE); 27 of 69 had non-RFP at rest and peak stress (AA). In EA, IVRT and EDT lengthened (by 43 ms and 46 ms), and tricuspid regurgitation (TR) decreased (by 26 mm Hg, p < 0.01), suggesting a fall in left atrial (LA) pressure. The stress response in AA was similar to EA. In EE, IVRT and EDT shortened (by 21 ms) and TR increased (by 13 mm Hg, p < 0.01), suggesting a rise in LA pressure. Peak aortic acceleration (LV inotropy) increased by 0.8 g in EA but only by 0.2 g in EE (difference p < 0.001). Median follow-up (interquartile range) was 34 (20 to 57) months. Three-year survival for EE, EA, and AA was 49%, 79%, and 89%, respectively (p < 0.001). Compared with AA, the hazard ratio for EE was 9.5 (p < 0.001) and for EA was 1.9 (p = 0.30). In ischemic cardiomyopathy, persistence of restrictive filling during stress implies a striking rise in LA pressure, greatly attenuated LV inotropic response, and markedly reduced survival. Stress echocardiography uniquely identifies these high-risk patients.


Corpus luteum development and function and relationship to pregnancy during the breeding season in the Mediterranean buffalo.
The aim of this study was to ascertain corpus luteum (CL) development and function in buffaloes synchronized and mated by artificial insemination (AI) during the breeding season. Italian Mediterranean buffalo cows (n = 43) at 86.5 ± 2.7 days postpartum were synchronized by the Ovsynch-TAI Program and inseminated using frozen thawed semen at 20 and 44 h after the second injection of GnRH. The CL dimensions (diameter and area) and blood flow were examined on Days 5, 10, 15, 20, and 25 after AI by realtime B-mode/colour-Doppler ultrasonography. The resistive index (RI), pulsatility index (PI) and time average medium velocity (TAMV) were recorded at each time, together with CL dimensions. Blood samples were taken on the days of ultrasonography for progesterone (P4) assay by RIA. Data were grouped into pregnant or non-pregnant and retrospectively analyzed by repeated measure ANOVA and correlation analyses. Dimensions of the CL on Days 10, 20, and 25 after AI were greater (P < 0.01) in buffaloes pregnant on Day 45 (n = 18) compared with non-pregnant buffaloes (n = 25). The former buffaloes also showed a greater (P < 0.01) rate of CL growth between Days 5 and 10 after AI. Blood flow to the CL on Day 10 after AI showed a higher TAMV (P < 0.01) and lower RI (P < 0.05) in pregnant buffaloes compared with non-pregnant buffaloes. Negative correlations were observed on Day 10 after AI between CL diameter and RI (r = -0.61; P < 0.01) and PI (r = -0.60; P < 0.01); P4 concentrations and RI (r = -0.46; P < 0.02); and RI and pregnancy (r = 0.45; P < 0.02). Positive correlations were observed between pregnancy and CL size (r = 0.54; P < 0.01), ΔCL diameter between Days 5 and 10 (r = 0.52; P < 0.01), ΔCL area between Days 5 and 10 (r = 0.48; P < 0.015), and ΔP4 between Days 5 and 10 (r = 0.50; P < 0.01). Based on these findings it is concluded that the period between Day 5 and 10 is very important for CL growth and crucial in evaluating pregnancy. Accordingly, the assessment of CL parameters during the period from Day 5 to Day 10 after AI might be used to predict the likelihood of an ongoing pregnancy.


Intracellular sorbitol content in isolated rat inner medullary collecting duct cells. Regulation by extracellular osmolarity.
In order to study the mechanisms involved in the regulation of renal inner medullary sorbitol content, collecting duct cells were isolated from rat inner medulla and the effect of extracellular osmolarity on sorbitol synthesis and sorbitol content was investigated. Cells isolated at 300 mosmol/l and incubated up to 24 h as primary cultures in 300 mosmol/l media or in media made 600 mosmol/l by the addition of 150 mM NaCl showed no difference in total synthesis. Intracellular sorbitol content was, however, 2.3-fold higher in the cells kept in the higher osmotic medium. Cells isolated at 600 mosmol/l released sorbitol about 8 times faster when transferred into hypoosmotic medium (300 mosmol/l) than when transferred into isoosmotic (600 mosmol/l) media. Cells exposed to hyperosmotic media (900 mosmol/l with NaCl) maintained a higher intracellular sorbitol content than cells incubated in isoosmotic media. Changes of intracellular sorbitol content could not be attributed entirely to cell lysis--as demonstrated by determination of cellular content of lactate and lactate dehydrogenase. The alteration in sorbitol membrane permeability was reversible and was only observed when poorly permeable solutes (such as NaCl and sucrose) were used for the experiments, changes in urea elicited no effect. It is proposed that rapid changes in membrane permeability to sorbitol play an important role in the adjustment of intracellular sorbitol concentration in inner medullary collecting duct cells to changes in extracellular osmolarity.


Long-term Outcomes Following Surgery for Infantile Nystagmus Syndrome With Abnormal Head Positioning.
To evaluate long-term outcomes of surgical treatment for abnormal head positioning (AHP) associated with infantile nystagmus syndrome (INS). Retrospective observational case series. Review of 150 patients who underwent surgery for AHP associated with nystagmus. Outcomes included head positioning, duction limitations, and strabismus, and were evaluated several times postoperatively. Successful collapse of AHP was defined as being ≤10°. Thirty-one patients had surgery for AHP in the pitch (chin up/down) position, whereas 119 had surgery for a horizontal AHP. In addition, 54 underwent 50%-60% augmentation, 19 underwent 40% augmentation, 5 underwent less than 40% augmentation. Thirty-eight had surgical dose modified to correct strabismus, and 3 underwent surgery different from standard Kestenbaum procedures. Collapse of AHP: At the 1-3-week follow-up (n = 131), 125 patients (95%) had collapse of AHP. The percentage trended down at the 2-5-month (91%, n = 106) and 2-year follow-ups (83%, n = 57). However, at 5 and 10 years, it was 93% (n = 42) and 93% (n = 14), respectively, due to reoperation in a small minority. Over- and undercorrection: At 1-3 weeks, 5% of patients were overcorrected whereas 0% were undercorrected. Over- and undercorrection rates peaked at 2 years postoperatively. Ten years out, there were no overcorrections and 7% undercorrections. Four percent of patients required reoperation for overcorrection (mean 2.7 years) and 5% did for undercorrection (mean 3.9 years). Surgery for the head positioning associated with INS produces excellent outcomes throughout 10 years postoperatively. Overcorrection presents early and resolves either over time or with additional surgery. Undercorrection develops later and can persist despite reoperation.


Strategy to small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion.
Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn's disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion. From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records. Six Crohn's disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1-2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab. The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used.


IR + VUV double resonance spectroscopy and extended density functional theory studies of ketone solvation by alcohol: 2-butanone·(methanol)n, n = 1-4 clusters.
Infrared plus vacuum ultraviolet (IR + VUV) photoionization vibrational spectroscopy of 2-butanone/methanol clusters [MEK·(MeOH)n, n = 1-4] is performed to explore structures associated with hydrogen bonding of MeOH molecules to the carbonyl functional group of the ketone. IR spectra and X3LYP/6-31++G(d,p) calculations show that multiple isomers of MEK·(MeOH)n are generated in the molecular beam as a result of several hydrogen bonding sites available to the clusters throughout the size range investigated. Isomer interconversion involving solvating MeOH rearrangement should probably occur for n = 1 and 2. The mode energy for a hydrogen bonded OH stretching transition gradually redshifts as the cluster size increases. Calculations suggest that the n = 3 cluster isomers adopt structures in which the MEK molecule is inserted into the cyclic MeOH hydrogen bond network. In larger structures, the cyclic network may be preserved.


The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro.
Oxidation of low density lipoprotein (LDL) is implicated in the development of atherosclerosis and dietary antioxidants may provide a useful therapy in the prevention of LDL oxidation and atheroma development. The aim of these experiments was to investigate the antioxidant activity of the soybean isoflavone, genistein, in in vitro models of LDL oxidation. Genistein inhibited copper-mediated oxidation of LDL in a concentration-dependent manner by lengthening the time for conjugated diene formation (54.1 +/- 5.1 min in control LDL and 107.1 +/- 1.8 min with 5 micromol/l genistein, P<0.001) and decreasing the oxidation rate (14.4 +/- 1.9 nmol conjugated diene/mg LDL protein/min in control LDL and 7.4 +/- 1.1 nmol conjugated diene/mg LDL protein/min with 5 micromol/l genistein, P<0.001). Peroxy radical (azo-initiated) oxidation of LDL was significantly inhibited by 200 micromol/l genistein as indicated by: (i) increase in the time required for malondialdehyde (MDA) formation (7 h incubation compared to 3 h incubation with control LDL), (ii) 32, 44 and 46% decreases in MDA concentration compared to control samples following 3, 4 and 5 h incubation, respectively and (iii) decrease in relative electrophoretic mobility (REM) of LDL. Incorporation of genistein into LDL and its resultant antioxidant activity was also investigated. LDL was isolated from plasma which had been pre-incubated with 25. 50 or 100 micromol/l genistein at 37 degrees C for 24 h. Approximately 3-4% of genistein present in plasma was incorporated into LDL, however copper-mediated oxidation of control LDL and LDL isolated from plasma pre-incubated with genistein was not significantly different.


Gene expression analyses on embryonic external genitalia: identification of regulatory genes possibly involved in masculinization processes.
Androgen plays a crucial role in initiating and maintaining the expression of male sexual characteristics in mammals. In humans and mice, any defects along the pathway of androgen functions result in congenital urogenital abnormalities. The genital tubercle (GT), an anlage of the external genitalia, differentiates into a penis in males and a clitoris in females. Although masculinization of the external genitalia is androgen-dependent, the molecular pathway of its potential downstream genes is largely unclear. To identify the genes involved in mouse GT masculinization, we performed gene expression analyses, such as real-time quantitative polymerase chain reaction and section in situ hybridization analysis. From our studies we have identified candidate genes, Cyp1b1, Fkbp51 and MafB as potential androgen targets during mouse GT masculinization.


Hormone selective lipase activation in the isolated rabbit heart.
The synthesis and release of PGs by the isolated perfused rabbit heart upon bradykinin stimulation results from lipase stimulation which liberates arachidonic acid for PG biosynthesis. The [14C]-labelled fatty acids, arachidonate, linoleate, and oleate, when infused into the heart preparation, were efficiently incorporated into the phospholipid pool in the heart mostly in the 2-position of phosphatidylcholine. On the other hand, [14C]-palmitate was esterified into both the 1- and the 2-position. Bradykinin released bioassayable PG when injected into the rabbit hearts, regardless of which fatty acid label was incorporated into the phospholipid pool. However, only [14C]-arachidonic acid (but not [14C]-linoleate, oleate or palmitate) was liberated from the variously labelled hearts upon hormone stimulation. This selective bradykinin effect on fatty acid release suggests that hormone stimulation either activates a specific lipase that distinguishes different fatty acids in the 2-position or activates lipase which is selectively compartmented with arachidonate-containing phospholipids. Ischemia, on the other hand, appeared to non-specifically stimulate tissue lipases, resulting in a non-selective release of oleic as well as arachidonic acid. A disproportionally large release of arachidonic acid was observed accompanying a relatively small PG (10:1 arachidonate: PG ratio) production during ischemia, as compared to bradykinin (3:1 ratio), suggesting distinct mechanisms for PG biosynthesis induced by bradykinin and ischemia.


Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.
Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.


Thermodynamic solubility product of human tooth enamel: powdered sample.
Solubility of human dental enamel in H3PO4 was studied in the pH range of 4.5 to 7.6. Thermodynamic solubility of the enamel mineral was calculated in terms of the ion activity product, (Ca2+)5(PO43-)3(OH-), for hydroxyapatite. The solubility product varied from 7.2 times 10(-53) to 6.4 times 10(-58) mol9 liter-9 depending on the cumulative amount of the dissolution of the solid in a series of repetitive sequences of solubility experiments.


Trends of tuberculosis case detection, mortality and co-infection with HIV in Ghana: A retrospective cohort study.
In an era of renewed commitment to accelerate the declines in Tuberculosis (TB) incidence and mortality, there is the need for National Tuberculosis Programmes (NTPs) to monitor trends in key indicators across a geographical location and to provide reliable data for direct measurement of TB incidence and mortality. In this context, we explored the trends of TB case detection, mortality and HIV co-infection, and examined the predictors of TB deaths in Ten districts of the Volta region of Ghana. We conducted a retrospective cohort study of all TB cases registered from 2013 to 2017 in 10 districts of the Volta Region of Ghana. Case detection rate (CDR) was computed as the ratio of the number of new and relapse TB case notified to NTP to the number of estimated incident TB cases in a given year. Case fatality rates were estimated using data from 2012-2016 cohort of TB patients. Simple and multiple logistic regression were used to identify predictors of TB deaths with odds ratios and 95% confidence intervals estimated. Overall, there were 3,735 new and relapse TB patients who commenced anti-TB treatment during the period, representing the case detection rate of 40.1% with district variations. The CDR remained stable during the 5 years. Of the total cases, HIV status was documented for 3,144 (84.2%), among whom, 712 (22.6%) were HIV positive. The TB/HIV co-infection was more prevalent among children under 15 years of age (30.1%), males (30.6%), treatment after lost to follow-up patients (33.3%), and smear-negative pulmonary TB patients (29.1%). The prevalence of TB/HIV co-infection did not significantly change over the years. The overall case fatality rate was 13% (n = 486), with considerable variation among HIV-positives and HIV-negative TB patients (21.8% and 11% respectively) (p<0.001) and among districts. TB/HIV co-infection, sputum smear-negative pulmonary TB and district of anti-TB treatment predicted TB mortality. TB case detection rate was low and remained stable during the study period, whereas co-infection with HIV and mortality rates were quite high, indicating the need for feasible strategies such as active case finding to improve case detection, and improved case management to reduce mortality.


Release of DR molecules from complexes with invariant chain through the formation of a C-terminal 25 kDa invariant chain fragment.
To investigate how class II major histocompatibility complex (MHC) molecules are released from complexes with invariant chain (Ii), we studied a 25 kDa Ii fragment (p25) detected by Western blotting in affinity chromatographed DR preparations. The p25 species corresponds to the non-transmembrane, C-terminal Ii fragment 107-232. It was determined by gel filtration chromatography that the p25 fragment has a relative molecular mass (M(r)) of 46 kDa, indicating that this Ii fragment is present as dimers in B cell lysate. Two independent approaches were followed to demonstrate that generation of the p25 fragment takes place shortly before, or concomitantly to, loading of class II MHC molecules with antigen fragments. First, it was shown that a fraction of the p25 molecules is resistant to endoglycosidase H digestion, indicating that the p25 polypeptide can exit the endoplasmic reticulum (ER) and is transported at least to the cis-Golgi compartment. Second, treatment of class II MHC-positive B cells with leupeptin blocks the formation of p25, further indicating that this Ii fragment is generated in the endosomal compartment. The role of the p25 Ii species in the assembly of complexes between peptides and DR molecules was then investigated. While the p25 fragment was totally unable to prevent binding of a synthetic tetanus toxin peptide to DR molecules, the full-length Ii species (p33/35) effectively inhibited peptide binding, indicating that, by contrast with the p33/35 species, the p25 fragment does not occlude the peptide binding site of DR molecules. We concluded that the p25 fragment, which is produced by proteolytic cleavage at the N-terminal side of Methionine 107, has a decreased affinity for DR molecules as compared with the p33/35 species. Dissociation of the p25 fragment from DR molecules exposes the peptide binding site, which is thus made accessible for antigen fragments. This model of the complexes between DR and antigen fragments proposes that a stretch of Ii prevents peptide binding by occluding the peptide binding site without directly occupying it.


Inhibition of Hsp90 and 70 sensitizes melanoma cells to hyperthermia using ferromagnetic particles with a low Curie temperature.
Heat shock protein (Hsp) 90 is a key regulator of various oncogene products and cell-signaling molecules, while Hsp70 protects against heat-induced apoptosis. We previously described a system in which hyperthermia was produced using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T c) of 43 °C to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, the antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor (quercetin) with FMP-mediated hyperthermia were examined. Expressions of Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMPs were then injected into the resultant tumors, and the mice were divided into groups treated with quercetin and/or 17DMAG with/without hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMPs increased and stabilized at the T c. The TUNEL method was used to determine whether hyperthermia induced apoptosis within tumors. In the group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor growth was significantly suppressed 20 days after FMP injection in vivo, compared with other treatment groups. The survival rates among tumor-bearing mice observed for a period of 40 days were significantly higher in the hyperthermia + quercetin + 17DMAG group. Combining Hsp90/70 inhibition with hyperthermia appears to increase their antitumor effects. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important implications for cancer treatment.


Phase I metabolism of imipramine by microsomes of small intestine in comparison with metabolism by liver microsomes.
The metabolism of imipramine was investigated by the incubation of C-14 labelled compound in Krebs-Ringer bicarbonate buffer with microsomes of small intestine and of liver from guinea pigs. Imipramine and its metabolites were extracted with chloroform, separated by TLC and determined quantitatively by direct scanning with a TLC Linear Analyzer. With intestinal microsomes, the following metabolites could be identified: DMI, 2-OH-IMP, IMP-N-oxide. DMI is the main metabolite. The same metabolites appeared after incubation with liver microsomes, but the proportions were different: the N-oxide formation was predominant, followed by N-demethylation and hydroxylation. The formation of DMI and 2-OH-IMP seems to follow Michaelis-Menten kinetics, both in assays with intestinal and with liver microsomes. The liver/intestine ratio of DMI and 2-OH-IMP formation is proportional to the cytochrome P-450 ratio in the microsomes, in contrast to N-oxide formation.


Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics.
Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.


The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax.
Mitochondria play a crucial role in programmed cell death via the intrinsic apoptotic pathway, which is tightly regulated by the B-cell CLL/lymphoma-2 (Bcl-2) protein family. Intracellular oxidative stress causes the translocation of Bax, a pro-apoptotic family member, to the mitochondrial outer membrane (MOM) where it induces membrane permeabilization. Oxidized phospholipids (OxPls) generated in the MOM during oxidative stress directly affect the onset and progression of mitochondria-mediated apoptosis. Here we use MOM-mimicking lipid vesicles doped with varying concentrations of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), an OxPl species known to significantly enhance Bax-membrane association, to investigate three key aspects of Bax's action at the MOM: 1) induction of Bax pores in membranes without additional mediator proteins, 2) existence of a threshold OxPl concentration required for Bax-membrane action and 3) mechanism by which PazePC disturbs membrane organization to facilitate Bax penetration. Fluorescence leakage studies revealed that Bax-induced leakage, especially its rate, increased with the vesicles' PazePC content without any detectable threshold neither for OxPl nor Bax. Moreover, the leakage rate correlated with the Bax to lipid ratio and the PazePC content. Solid state NMR studies and calorimetric experiments on the lipid vesicles confirmed that OxPl incorporation disrupted the membrane's organization, enabling Bax to penetrate into the membrane. In addition, 15N cross polarization (CP) and insensitive nuclei enhanced by polarization transfer (INEPT) MAS NMR experiments using uniformly (15)N-labeled Bax revealed dynamically restricted helical segments of Bax embedded in the membrane, while highly flexible protein segments were located outside or at the membrane surface.


MIB1 as a possible predictor of recurrence in low-grade endometrial stromal sarcoma of the uterus.
Immunohistochemical analysis of MIB1, p53, estrogen, and progesterone receptors can provide prognostic information in endometrial adenocarcinoma. Since predictors of recurrence for low-grade endometrial stromal sarcoma (LESS) are still unknown, a battery of immunostains was performed to find markers, which might be useful to predict prognosis. Eleven patients with an average age of 43.8 years (range 27-76) were identified with stage I LESS. Immunostains, including MIB1, p53, ER, and PR, were evaluated by two pathologists, independently. All tumors were positive for ER and PR; 1/11 was positive for p53; MIB1 ranged from 0 to 20% positive tumor nuclei. Mitotic counts ranged from 0 to 7/10 hpf. Two patients developed recurrences. One had a pelvic recurrence 7 years after diagnosis. This tumor had a mitotic count of 1/10 hpf, MIB1 expression in 10% of nuclei, and focal p53 expression. A second patient developed pulmonary metastases 10.8 years after diagnosis; the tumor showed a mitotic count of 7/10 hpf and MIB1 expression in 20% of nuclei, but was negative for p53. There was a significant difference in MIB1 reactivity scores between patients who did or did not develop recurrence (P = 0.0303). A marginally significant association was detected between MIB1 (P = 0.0896) or p53 (P = 0.0833) positivity and length of recurrence-free survival. Although MIB1 and p53 appear to be useful prognostic markers, a larger study would be necessary to confirm their validity.


Adenine for guanine substitution -78 base pairs 5' to the apolipoprotein (APO) A-I gene: relation with high density lipoprotein cholesterol and APO A-I concentrations.
A common mutation, adenine (A) for guanidine (G) substitution (G/A) has been located -78 bp 5' to the apo A-I gene. This region has been shown to be involved in the transcriptional regulation of the apo A-I gene. Previous studies have shown that this mutation is associated with altered high density lipoprotein cholesterol (HDL-C) levels, although these findings have not been consistent. We have studied the frequency of this mutation in 125 subjects (60 males and 65 females) selected because they had HDL-C levels below the 25th (low HDL) or above the 75th (high HDL) percentile of the population distribution. The presence of the mutation was detected by Msp I digestion of a 259 bp fragment of PCR amplified DNA. The allele frequency was similar in both groups (0.20 for the lowest HDL group and 0.28 for the highest HDL group, p > 0.05), although a non-significant trend was observed in a higher frequency of the A/A genotype in the highest HDL females (17.5%) vs only 6.7% in the lowest HDL female group. In conclusion, in this population the G/A mutation was not significantly associated with HDL-C or apo A-I plasma levels.


Epstein-Barr virus-positive mucocutaneous ulcer mimicking sigmoid colon adenocarcinoma.
Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) belongs to a spectrum of EBV-associated lymphoproliferative disease. We present the case of an 89-year-old female with seronegative polyarthritis treated for several years with methotrexate (12.5 mg weekly). She also had asthenia, anorexia and a positive fecal immunohistochemical test. In view of the above, a colonoscopy was performed that revealed a polypoid mass with a malignant appearance in the sigmoid colon, which prevented the passage of the endoscope and was suggestive of colonic adenocarcinoma (CAC).


A new approach to the study of urinary macromolecules as a participant in calcium oxalate crystallization.
Despite intense investigation, the relationship of urinary proteins to urinary stone matrix formation remains poorly understood. In an attempt to gain more information regarding this interaction, the binding of urinary proteins to calcium oxalate crystals formed in urine in vitro was studied. 0.1 M calcium chloride and 0.1 M sodium oxalate were added to an aliquot of urine collected from five non-infected, non-stone forming males. The resulting calcium oxalate crystals were centrifuged and the pellet demineralized with 5% EDTA. Gel filtration chromatography was used to isolate the protein fraction from the urine samples before and after crystallization of calcium oxalate. The proteins recovered from the crystals and urine were separated by two-dimensional polyacrylamide gel electrophoresis. Many, but not all of the urinary proteins were bound by the crystals. Albumin, seen to the most abundant urinary protein, was absent or markedly diminished in all instances, and the second most abundant urinary protein, PC-30, became the predominant protein component of the crystals. An unidentified protein with approximate molecular weight of 22,000 daltons and isoelectric point of 6.4 was highly concentrated by the crystals even when undetected in the urine. The study suggests that the binding of urinary proteins to calcium oxalate crystals formed in urine in vitro is not a random event but rather a selective phenomenon.


[Portable ultrasonographic device and bladder dysfunction management in stroke patients].
To determine the usefulness of a portable ultrasonographic device in the management and rehabilitation of stroke patients' bladder voiding impairment in the early stage and to propose a well-fitted screening protocol. A prospective observational study of 33 inpatients admitted into our stroke rehabilitation program. A urinary elimination assessment protocol defines the criteria of intermittent catheterization. The determination of bladder volume was performed with a Bladderscan BVI 3000 portable ultrasonographic device. Urinary retention was present in ten of the 33 patients at admission, who were started on one or many intermittent catheterizations. Retention was resolved for seven of them at discharge. The portable ultrasonographic device allows a very accurate bladder volume assessment, especially useful in at-risk patients: those with cognitive impairments, diabetes mellitus, and prestroke urinary pathology. A new version of our first screening protocol increases the ability to detect patients with true urinary retention. Results are discussed according to the literature data. The portable ultrasonographic device is a simple and noninvasive tool, useful for diagnosis, follow-up and therapy guidance of urinary retention after stroke. An adapted protocol is proposed in order to assess and rehabilitate this trouble. The goal is to avoid long-term catheterization and its linked infectious risk.


A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case report and literature review.
Spinocerebellar ataxia (SCA), a genetically inherited heterogeneous disorder, is characterized by gait ataxia, dysarthria, parkinsonism, choreic movements, dystonia, epilepsy, cognitive and psychiatric symptoms. Spinocerebellar ataxia-42 (SCA42), caused by heterozygous mutation in the calcium channel 1G (CACNA1G) gene, is a rare SCA subtype and the transmission pattern is autosomal dominant inheritance. We presented a novel mutation (c.4721T>A; p.Met1574Lys) in 3 patients from a Chinese family using whole-exome sequencing. All patients exhibited cerebellar ataxia and the clinical manifestations were similar to those that were previously reported in the French and Japanese families. In addition, cerebral magnetic resonance imaging (MRI) showed cerebellar atrophy, and the hot cross bun sign of brainstem was found in the proband and her sister. The clinical features and MRI findings indicated the diagnosis of SCA. Taken together, the symptoms, MRI findings, as well as whole-exome sequencing made the diagnosis of SCA42 most likely candidate. The patient was treated with cobamamide (1.5 mg once daily) for nerve nutrition and further physical therapy. At the 4-month follow-up visit, the patient's condition did not improve obviously. Recently, a missense mutation in CACNA1G gene (c.5144G4A; p.Arg1715His) was identified in French and Japanese families with SCA42. However, there has been no report of SCA42 or its mutant loci in Chinese patients. Our finding showed a novel mutation in CACNA1G gene and provided important insights into the pathogenesis of SCA42.


Nutritional status in patients with active pulmonary tuberculosis and new nutritional risk screening model for active tuberculosis: a national, multicenter, cross-sectional study in China.
Tuberculosis (TB) remains a significant challenge for public health and is closely associated with malnutrition; however, few studies have attempted to screen malnutrition among TB patients. The study aimed to evaluate the nutrition status and build a new nutritional screening model for active TB. A retrospective, multicenter, large cross-sectional study was conducted in China from 1 January 2020 to 31 December 2021. All included patients diagnosed with active pulmonary TB (PTB) were evaluated both by Nutrition Risk Screening 2002 (NRS 2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Univariate and multivariate analyses were conducted to screen the risk factors associated with malnutrition, and a new screening risk model, mainly for TB patients, was constructed. A total of 14,941 cases meeting the inclusion criteria were entered into the final analysis. The malnutrition risk rate among PTB patients in China was 55.86% and 42.70%, according to the NRS 2002 and GLIM, respectively. The inconsistency rate between the two methods was 24.77%. A total of 11 clinical factors, including elderly, low body mass index (BMI), decreased lymphocyte cells, taking immunosuppressive agents, co-pleural TB, diabetes mellitus (DM), human immunodeficiency virus (HIV), severe pneumonia, decreased food intake within a week, weight loss and dialysis were identified as independent risk factors of malnutrition based on multivariate analyses. A new nutritional risk screening model was constructed for TB patients with a diagnostic sensitivity of 97.6% and specificity of 93.1%. Active TB patients have severe malnutrition status according to screening by the NRS 2002 and GLIM criteria. The new screening model is recommended for PTB patients as it is more closely tailored to the characteristics of TB.


High-performance sodium dodecyl sulfate polyacrylamide gel capillary electrophoresis of peptides and proteins.
High-performance capillary sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) has been developed for the separation and molecular weight (MW) determination of peptides and proteins. In this work, acrylamide was polymerized in fused-silica capillaries of 75 microns I.D. and 10 or 20 cm length. On-line UV detection was employed by placing the capillary in the optical path of the detector. Rapid separations of myoglobin fragments and of a mixture of standard proteins were demonstrated with efficiencies of the order of 40,000 plates for a column, 20 cm in length. Linear plots of log MW vs. mobility for the SDS protein complexes were observed. Variation in the percentage monomer composition (% T) of the polyacrylamide yielded the expected common intercept of log mobility vs. % T, confirming the size separation mechanism in the gel capillaries. The separation of the A and B chains of insulin with a 10-cm column in less than 10 min was also demonstrated.


How does ethnicity affect the association between obesity and diabetes?
To examine the utility of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHR) in assessing diabetes risk across different ethnic groups. Cross-sectional analysis of data for eight ethnic groups from the 2003-2004 National Health and Nutrition Examination Survey and 2003-2004 Health Survey for England was performed. In 11 624 adults > or = 20 years old, self-reported as US White, US Black, Mexican American, English White, English Black, Bangladeshi, Pakistani, Indian or Chinese the presence of diabetes, defined as self-report of doctor diagnosis or glycated haemoglobin (HbA1c) > 6.1%, was ascertained. Comparisons of proportions were made using chi2-tests. Receiver operating characteristic (ROC) curves were calculated for BMI, WC and WHR predicting diabetes. Other ethnic groups had a higher prevalence of diagnosed diabetes than English Whites. The crude prevalence of diabetes in English Whites of normal weight (BMI < 25 kg/m2) was 3.4%. Higher prevalences were seen in other ethnic groups (5.0-10.9%). Based on ROC curves, both WC and WHR had better discriminating ability for diabetes than BMI for both genders and some ethnic groups. Ethnic differences exist in the crude prevalence of diabetes, even in those characterized as normal weight by BMI. Thus, clinicians need to exercise caution in interpreting diabetes risk associated with a normal BMI. The use of other anthropometric measures, such as WC or WHR, may improve risk determination across different ethnic groups. More research is needed to determine the thresholds for different anthropometric measures that improve diabetes risk determination.


TREM2 knockdown improves the therapeutic effect of PD-1 blockade in hepatocellular carcinoma.
Triggering receptor expressed on myeloid cells 2 (TREM2), which is typically expressed in microglia/macrophage, is a crucial receptor modulating the activation of immune cells. Recent single-cell RNA sequencing studies of the tumor microenvironment (TME) have found that TREM2 is highly expressed in several subgroups of tumor-associated macrophages (TAMs) with immunosuppressive activity. TREM2 knockout mice are more resistant to tumor growth than wild-type mice in multiple mice tumor models. But the function of TREM2 expression in TAMs of hepatocellular carcinoma (HCC) is still unclear. Here we used a self-complementary adeno-associated virus (scAAV) with macrophage tropism to efficiently knockdown TREM2 in TAMs in vivo and found that the growth of hepatocellular carcinoma was suppressed by TREM2 knockdown. Moreover, we found that TREM2 knockdown remodeled TAMs to an immune-stimulating status and enhanced the therapeutic effect of PD-1 immune-checkpoint blockade in HCC.


Sizing silver nanoparticles in chicken meat using direct slurry sampling graphite furnace atomic absorption spectrometry.
Recently, graphite furnace atomic absorption spectrometry (GFAAS) has been suggested as a tool for detection and sizing of metal nanoparticles (NPs) providing several advantages, such as direct analysis of solid samples, high sample throughput, and robust and cost-efficient instrumentation. For this purpose, evaluation of newly introduced criteria of the absorbance signal, namely, atomization delay (tad) and atomization rate (kat), is performed. However, in real samples, NPs are typically stabilized by either engineered coating reagents or natural materials and occur in unknown concentration. Hence, systematic investigation of possible influences of nine different coating reagents and of Ag concentration on the atomization behavior of silver nanoparticles (AgNPs) was studied. Evaluation of absorption signal characteristics revealed no influence of the coating or Ag concentration on the observed parameters. Furthermore, size-dependent measurements gave reproducible size correlation independent from the coating. Validity of sizing AgNPs with the proposed approach was successfully proven by investigation of two reference materials. The found size of 74.3 ± 5.9 nm in RM 8017 (NIST) agrees very well with the certified size of 74.6 ± 3.8 nm. Moreover, AgNP size of 25.1 ± 2.5 nm found by direct slurry sampling GFAAS in matrix reference material "NanoLyse13"-chicken meat homogenate spiked with PVP-AgNPs-was in very good agreement with the reference value of 27.3 ± 5.3 nm as determined by TEM.


Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model.
To assess, using an in vivo engraftment strategy combining bone marrow cell (BMC) transplantation and tissue cardiomyoplasty, the functional outcome of distinct vascular progenitor cell therapy (endothelial progenitor (EPC) and mesenchymal stem (MSC) cells) at distance of myocardium infarction (MI). The study was also designed to test whether scaffold mixing progenitors with unfractionated BMC could improve progenitor recruitment in the damaged myocardium. To track engrafted progenitor cells in vivo, cultured murine MSC and EPC were transduced with eGFP lentiviruses. Thirty days after cryogenical induction of MI, C57BL/6J mice were randomized to receive muscle patch placement coated or not (control group), labeled EPC or MSC mixed to the ration of 1:10, or not with unfractionated BMC. Two weeks after transplantation, cardiac function was recorded and heart sections were examined to detect GFP-labeled progenitor cells and analyze cell differentiation. This study showed that either type of mono cell therapy improved angiogenesis and cell survival in the scar but only MSC exhibited the capacity to invade the scar. We found no evidence of myocardial or vascular regeneration from progenitor cells. Engraftment of the progenitors/unfractionated BMC mix increased repopulation and thickness of the scar. Combined therapy with unfractionated BMC and expanded MSC appeared thus promising for scar repopulation.


[Management of atrial fibrillation in patients with cardiac stimulators or defibrillators: the possibilities of telemonitoring].
Some cardiac stimulators and defibrillators can be followed by telemonitoring. Telemonitoring permits diagnosis of atrial fibrillation episodes, which are frequently asymptomatic. Combination of holter memories with telemonitoring gives numerous informations about arrhythmias occurring. This can help to optimize rhythm control, rate control or anticoagulation. Examples issued from practice are presented in this article.


Mechanisms of induction of enzymes that protect against chemical carcinogenesis.
A persuasive body of evidence indicates that substantial protection against chemical carcinogenesis can be achieved by induction of enzymes concerned with the metabolism of carcinogens. There are two classes of anticarcinogenic enzyme inducers: (a) monofunctional inducers (e.g., phenolic antioxidants, isothiocyanates, coumarins, thiocarbamates, cinnamates, 1,2-dithiol-3-thiones) that elevate Phase II enzymes (such as glutathione S-transferases, NAD(P)H:quinone reductase, UDP-glucuronosyl-transferases) in various tissues without significantly raising the Phase I enzyme, aryl hydrocarbon hydroxylase (cytochrome P1-450); and (b) bifunctional inducers (e.g., polycyclic aromatic hydrocarbons, flavonoids, and azo dyes) that induce both Phase I and Phase II enzymes of xenobiotic metabolism. Induction of Phase II enzymes appears to be a sufficient condition for achieving chemoprotection, and since certain Phase I enzymes are responsible for activating carcinogens to their ultimate reactive forms, selective Phase II enzyme inducers offer intrinsically safer prospects for achieving chemoprotection. Whereas induction of both Phase I and II enzymes by bifunctional inducers depends on the Ah receptor, induction of Phase II enzymes by monofunctional inducers is independent of a functional Ah receptor. Studies on the structural requirements for induction of quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase; EC 22.214.171.124] by monofunctional inducers in Hepa 1c1c7 murine hepatoma cells have revealed that such inducers contain a distinctive chemical feature (or acquire this feature by metabolism) that regulates the synthesis of this protective enzyme. The inducers are all Michael reaction acceptors characterized by olefinic (or acetylenic) linkages that are rendered electrophilic by conjugation with electron-withdrawing groups. Typical examples are alpha, beta-unsaturated aldehydes, ketones (including quinones), thioketones, sulfones, esters, nitriles and nitro groups. The potency of these inducers parallels their reactivity as Michael acceptors. These generalizations have provided mechanistic insight into the vexing question of how so many seemingly unrelated anticarcinogens induce chemoprotective enzymes. They have also led to the prediction of entirely new and unsuspected structures of inducers, with potential for chemoprotective activity.


Studies on the development of cell contacts and of the intercellular matrix during decidualization in the rat.
Cell contacts between developing decidual cells were examined in thin sections and in replicas of freeze-cleaved tissue of rat uterus. At the time of implantation only puncta adhaerentia were found between stromal cells. Gap junctions appeared 24 h after decidualization and thereafter increased in number and extent. Thus, there is little morphological evidence for a propagation of the initial stimulus for decidualization via gap junctions. An increase in amorphous, extracellular material is noted after decidualization with a concomitant decrease of collagen fibers. This amorphous material probably represents fibrinoid.


Chest Wall Pain after Minor Trauma.
A 30-year-old healthy male presented with a complaint of chest pain after mild thoracic trauma sustained while rescuing stranded flood victims during Hurricane Harvey. Careful physical examination revealed a tender palpable cord along the lateral aspect of his chest consistent with a superficial thrombophlebitis. Mondor's disease is a superficial thrombophlebitis with myriad underlying causes that can involve the thoracic wall. Although Mondor's disease has been well described in the literature, this case describes a unique presentation in an austere environment with blunt trauma as the underlying cause.


Three-dimensional elliptical reconstruction for stereoscopic magnetic resonance angiography.
Stereoscopic MRA acquires a pair of blood vessel projections at two different viewing angles. Previously, we have developed two algorithms to reconstruct 3-D blood vessels from stereoscopic MRA. The assumption we made was that blood vessels were tilting circular tubes and the shape of the vessel on every cross-section was an ellipse. Since an ellipse can be represented in either algebraic form or parametric form, our previous algorithms reconstructed the ellipses by representing them in these two forms. In this paper, we further improved the accuracy of our previous algorithms by an order through two enhancements. The first improvement we made was a better method to estimate the rotation angle of the major axis of an ellipse. Instead of using the center of two adjacent ellipses to estimate the rotation angle as in our previous method, the new method used the projection lengths of the two views to estimate the angle. The second improvement we made was the equation to describe the relationship between the major/minor axes and the projection lengths. In our experiments, the average estimation error for the parametric algorithm was improved from 0.471 pixels to 0.066 pixels. The average error for the algebraic algorithm was improved from 0.101 pixels to 0.014 pixels.


[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].
Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one.


Influence of lime and struvite on microbial community succession and odour emission during food waste composting.
Lime addition as well as formation of struvite through the addition of magnesium and phosphorus salts provide good pH buffering and may reduce odour emission. This study investigated the odour emission during food waste composting under the influence of lime addition, and struvite formation. Composting was performed in 20-L reactors for 56days using artificial food waste mixed with sawdust at 1.2:1 (w/w dry basis). VFA was one of the most important odours during food waste composting. However, during thermophilic phase, ammonia is responsible for max odour index in the exhaust gas. Trapping ammonia through struvite formation significantly reduced the maximum odour unit of ammonia from 3.0×104 to 1.8×104. The generation and accumulation of acetic acid and butyric acid led to the acidic conditions. The addition of phosphate salts in treatment with struvite formation improved the variation of total bacteria, which in turn increased the organic decomposition.


Tibial Tubercle Osteotomy May Not Provide Additional Benefit in Treating Patellar Dislocation With Increased Tibial Tuberosity-Trochlear Groove Distance: A Systematic Review.
To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 55-83). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-with-MPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. Level IV, systematic review of Level II to IV studies.


[Extremely rapid progression of oral cavity carcinosarcoma].
Carcinosarcoma is a very rare malignant tumor of the salivary glands including accessory salivary gland, associating malignant mesenchymal and epithelial tissue. It usually occurs after 50 years of age. Its prognosis is very poor. We present a case of carcinosarcoma having evolved extremely rapidly. A 38-year-old female patient presented with an inflammatory budding lesion of the mandibular gingival mucosa. The diagnosis of carcinosarcoma having developed from an accessory salivary gland was made after testing biopsies. The carcinosarcoma could not be removed because of an extremely rapid tumor growth, its volume having increased three fold in 2 weeks. The patient died in a few weeks. The occurrence of carcinosarcoma at 38 years of age is exceptionally rare. The rapidly evolution of carcinosarcoma is well documented. It may prevent complete excision. This case led us to suggest an emergency management for carcinosarcomas.


Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.
Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. This was a cross-sectional case control study. The study was conducted at a clinical research center. Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Blood samples and anthropometric measures were obtained. LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.


Identification of Hsp90 as a species independent H5N1 avian influenza A virus PB2 interacting protein.
The avian influenza polymerase protein PB2 subunit is an important mediator of cross species adaptation and adaptation to mammalian cells is strongly but not exclusively associated with an adaptive mutation of the codon at position 627 of the PB2 protein which alters the glutamate normally found at this position to a lysine. This study sought to identify host cell factors in both mammalian and avian cells that interacted in a species specific or species independent manner. Two PB2 fusion proteins differing only in codon 627 were generated and transfected into mammalian and avian cells and interacting proteins identified through co-immunoprecipitation. A number of proteins including Hsp90 were identified and further investigation showed that Hsp90 interacted with both isoforms of PB2 in both mammalian and avian cells. Hsp90 is thus identified as a species independent interacting protein, further confirming that this protein may be a suitable target for anti-influenza drug development.


Relationship among four Big Five measures of different length.
This study examined the relationship between three short measures of the Big Five. 100 participants completed the 60-item NEO-FFI, the 10-item Personality Inventory, the 5-item Single-Item Measure of Personality, as well as estimating their own NEO-FFI score. Correlations varied from r = .30 to .75. Concerns and advantages of short measures are discussed.


Involvement of nitric oxide in the potentiation of neurogenic contraction by manganese and nickel ions in mouse urinary bladder.
Repetitive electrical field stimulation evoked muscle contractions of the isolated mouse detrusor strips, which could be abolished by tetrodotoxin (TTX). Both Mn2+ and Ni2+ (0.01-0.06 mM) enhanced neurogenic detrusor contractions in high Ca2+ (5 mM) medium. The non-cholinergic component of the evoked detrusor contractions (in the presence of atropine) was specifically sensitive to this enhancing effect by either Mn2+ or Ni2+. In contrast, the cholinergic component in alpha,beta-methylene ATP-treated detrusors remained unaffected. As compared with Mn2+ and Ni2+, other metal ions, Cu2+, Co2+, Cd2+ and UO2(2+), failed to enhancing the non-cholinergic component of neurogenic detrusor contractions. Nitric oxide synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester and 7-nitroindazole (a selective neuronal NOS inhibitor) markedly inhibited the enhancing effect by either Mn2+ or Ni2+ on the neurogenic detrusor contractions. Moreover, Mn2+ and Ni2+ did not affect the contractions induced by either carbachol or alpha,beta-methylene ATP. It is concluded from these findings that the neuronal NOS-NO generation pathway is apparently involved in the enhancing effect of Mn2+ and Ni2+ on the muscle contractions elicited by excitatory non-cholinergic neurotransmission in the mouse detrusor strips.


DSIP-like immunoreactivity in the developing rat brain.
Delta sleep-inducing peptide (DSIP) is a naturally occurring nonapeptide that has been reported to affect sleep. The concentration of DSIP-like material was measured by a highly specific radioimmunoassay in brain tissue from developing rats. DSIP-like immunoreactivity was present in fetal brain at increased levels shortly before birth. In one experiment, a significant elevation in the concentration of the peptide occurred at postnatal day 20, but in a second, similar, study the increase occurred later. No marked differences in the levels of DSIP-like immunoreactivity were found in the brains of rats injected 2 months earlier with DSIP or among 10 parts of brains obtained at postnatal day 20. Regardless of the function of DSIP, it is available to the rat throughout early development.


Reconsideration of the concept of enhanced static fusimotor drive in rigidity in patients with Parkinson's disease.
The electromyographic responses elicited in the first dorsal interosseus muscle by small muscle stretches or by electrical stimulation of the median nerve were investigated in parkinsonian patients and in age-matched healthy subjects. Stimuli were applied during a steady level of contraction in the intrinsic hand muscle. This ensured comparable levels of excitability in the alpha-motoneurone pool in patients and normals. It was found that the normal short-latency stretch reflex was almost absent in rigid patients, while responses to electrical stimulation of low-threshold nerve fibres were of equal size in both groups. This result suggests that there is a change in fusimotor control of muscle spindles in Parkinson's rigidity without alteration of the central gain of the Ia-transmitted stretch reflex.


Role of capsule endoscopy Pillcam COLON 2 in patients with known or suspected Crohn's disease who refused colonoscopy or underwent incomplete colonoscopic exam: a case series.
Almost 70-80 % of patients with Crohn's disease and virtually all patients with ulcerative colitis have colorectal mucosa involvement. Colon capsule endoscopy is an interesting option for patients unable or unwilling to undergo colonoscopy. We report our experience with the second-generation colon capsule PillCam(®) COLON 2 in the detection of significant lesions in patients with known or suspected Crohn's disease, who refused colonoscopy or underwent incomplete colonoscopic exam. We have retrospectively reviewed the results of capsule endoscopy in 6 patients who refused colonoscopy (n = 3) or underwent incomplete colonoscopic exam (n = 3) between March 2011 and October 2012. In all patients, a CT scan was obtained before capsule endoscopy to rule out significant stenosis. In our series of 6 patients, 4 had both small bowel and colonic involvement. The use of the PillCam(®) COLON 2 capsule allowed a thorough examination and evaluation of the mucosal lesions with high acceptability, the method being perceived as noninvasive by the patients. No adverse events related to the capsule or bowel preparation were recorded. In this patient population, PillCam(®) COLON 2 capsule endoscopy was safe. The capsule findings had an important impact on treatment decisions and patient management.


Involvement of the periaqueductal gray in the hypotensive response evoked by L-glutamate microinjection in the lateral hypothalamus of unanesthetized rats.
The lateral hypothalamus (LH) is involved in cardiovascular control. L-glutamate (L-glu) stimulation of the LH of unanesthetized rats evoked hypotensive responses without significant heart rate changes. The neuronal pathway that mediates this response is unknown. There is evidence that the periaqueductal gray (PAG) is involved in the mediation of hypotensive responses evoked by electrical stimulation of the LH. In the present study, we attempted to verify the effect of an acute and reversible pharmacological ablation of the PAG with lidocaine or CoCl(2) on the hypotensive response caused by L-glu injection in the LH of unanesthetized rats. Microinjection of the local anesthetic lidocaine or the unspecific synaptic blocker CoCl(2) in the PAG significantly attenuated the hypotensive effects of L-glu stimulation of the LH, indicating the involvement of local synapses within the PAG in the hypotensive pathway activated by LH glutamatergic receptors. Microinjection of the neuronal tracer biotinylated dextran amine (BDA) in the PAG labeled neuronal cell bodies in the LH, indicating the existence of direct connections between these areas. In conclusion, the present results indicate that the hypotensive response evoked by L-glu stimulation of LH may involve a synaptic relay in the dorsal PAG.


Fibromuscular dysplasia of cardiac conduction system arteries in traumatic and nonnatural sudden death victims aged 0 to 40 years: a histological analysis of 100 cases.
Since 1967, numerous case reports have described fibromuscular alterations of the sinus node artery and/or the atrioventricular node artery as a potential cause of death. However, the prevalence of these changes in a healthy population has only rarely been investigated systematically. The arteries of the cardiac conduction system were studied systematically, by means of routine histology, in 100 cases of victims aged 0 to 40 years with a nonnatural cause of death. Microscopic alterations were seen in the walls of sinus node arteries in 52 out of 100 cases, in the walls of atrioventricular node arteries in 63/100 cases, and in the walls of small vessels in 60/100 cases. The results demonstrate that microscopically detectable findings of the cardiac conduction system arteries similar to fibromuscular dysplasia do not indicate a defined disease and should not be considered as a cause of death when there are no macroscopic findings in the coronary arteries.


A marker of human foetal endoderm defined by a monoclonal antibody involves Type 1 blood group chains.
This report demonstrates that a marker of human embryonic endoderm and embryonal carcinoma cells recognized by a hybridoma antibody FC 10.2, involves Type 1 blood group chains with the sequence Gal beta 1 leads to 3G1cNAc beta 1 leads to 3Gal beta 1 leads to 4G1c. This conclusion has been reached from antigenic analyses of meconium, ovarian cyst glycoproteins, oligosaccharides and glycolipids having Type 1 or Type 2 blood group chains. From knowledge of saccharide sequences and blood group related antigens in gastrointestinal tissues of man, we deduce that the 'disappearance' of FC 10.2 antigen from the normal, differentiated cells of the adult may result from masking by additional glycosylations or other substitutions.


Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05.
To determine if the addition of bromodeoxyuridine (BrdUrd) to radiotherapy prolongs survival when compared to radiotherapy alone in patients with brain metastases. Seventy-two patients with brain metastases were randomized to 37.5 Gy in 15 fractions of 2.5 Gy or to the same dose with BrdUrd 0.8 g/m2 per day for 4 days of each of 3 weeks. Drug treatment was begun on Thursday or Friday before the first week of radiotherapy. Patients had a Karnofsky performance score of at least 70, a neurological function classification of 1 or 2, and any primary tumor except central nervous system (CNS), leukemia, or lymphoma. The primary was absent, controlled, or under active radiotherapy. Patients were free of other metastases. They were stratified by primary site (breast, lung or other), number of metastases (single or multiple) and age (< 60 vs. > 60). There was no significant difference between the two treatment arms (p = 0.904). The study was open from October 1989 to March 1993 and accrued 72 patients. Only one patient in the RT only arm remains alive. The two treatment arms were balanced with respect to all stratification variables. Toxicity due to radiotherapy was similar in both arms. BrdUrd caused significant Grade 4 and 5 hematologic and skin toxicity in five patients. Two patients died due to hematologic toxicity and one from a Stevens-Johnson type skin reaction. Phenytoin played a role in the skin reactions and ranitidine was associated with the hematologic deaths. Ranitidine was eliminated, BrdUrd was discontinued after any hematologic toxicity, and no further Grade 4 or 5 toxicities were seen. The median survival was 6.12 months in the radiotherapy group and 4.3 in the BrdUrd group (p = 0.904). Patients with solitary brain metastases had significantly better survival (p = 0.031). BrdUrd did not enhance the efficacy of the radiotherapy regimen tested, in spite of the fact that brain metastases have shown high labeling indices. The toxicity of this schedule of BrdUrd administration was apparently increased by ranitidine and phenytoin.


Heritability and genomics of gene expression in peripheral blood.
We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (∼777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.


Stool chymotrypsin activity measured by a spectrophotometric procedure to identify pancreatic disease in infants.
The aim of this study was to assess the analytical performance of the BMC stool chymotrypsin test and its accuracy in diagnosing pancreatic disease in infants. The test utilizes a detergent which solubilizes chymotrypsin bound to stool residues, and a tetrapeptide coupled to p-nitroaniline which is specifically cleaved by chymotrypsin. We employed the IL Multistat at 30 degrees C to monitor enzyme activity as an increase in absorbance at 405 nm. The reaction was linear to 600 U/g stool. Recovery of exogenous chymotrypsin with a single detergent extraction was 98-105%, and of endogenous chymotrypsin (as determined by multiple extractions) 80-97%. Imprecision (CV) was 2.2% within-day and 2.4% between-day for the BMC control, and 2.4-5.2% for stool chymotrypsin in the range 8.3-14.4 U/g. Since the test utilises only 100 mg of stool, inhomogeneity of enzyme distribution was assessed by multiple assays on a single stool, which revealed a range of activity from 4.2-150%. We therefore recommend sampling of each stool in triplicate. With this procedure, chymotrypsin was measured in 220 consecutive stool samples submitted for fat determination from children. Applying the manufacturer's lower reference limit of 4.1 U/g, the following results were obtained (number abnormal/total number): suspected intestinal disease with normal stool fat (5/127); proven intestinal disease and increased stool fat (1/26); untreated cystic fibrosis (CF) with (19/22), and without (0/3) steatorrhea; CF with pancreatic insufficiency on replacement therapy (4/42).(ABSTRACT TRUNCATED AT 250 WORDS)


Agency alters perceptual decisions about action-outcomes.
Humans experience themselves as agents, capable of controlling their actions and the outcomes they generate (i.e., the sense of agency). Inferences of agency are not infallible. Research shows that we often attribute outcomes to our agency even though they are caused by another agent. Moreover, agents report the sensory events they generate to be less intense compared to the events that are generated externally. These effects have been assessed using highly suprathreshold stimuli and subjective measurements. Consequently, it remains unclear whether experiencing oneself as an agent lead to a decision criterion change and/or a sensitivity change. Here, we investigate this issue. Participants were told that their key presses generated an upward dot motion but that on 30 % of the trials the computer would take over and display a downward motion. The upward/downward dot motion was presented at participant's discrimination threshold. Participants were asked to indicate whether they (upward motion) or the computer (downward motion) generated the motion. This group of participants was compared with a 'no-agency' group who performed the same task except that subjects did not execute any actions to generate the dot motion. We observed that the agency group reported seeing more frequently the motion they expected to generate (i.e., upward motion) than the no-agency group. This suggests that agency distorts our experience of (allegedly) caused events by altering perceptual decision processes, so that, in ambiguous contexts, externally generated events are experienced as the outcomes of one's actions.