Genetic variants in loci 1p13 and 9p21 and fatal coronary heart disease in a Norwegian case-cohort study.
Single nucleotide polymorphisms (SNPs) in loci 1p13 and 9p21 have previously been found to be associated with incident coronary heart disease (CHD). This study aimed to investigate whether these SNPs show associations with fatal CHD in a population-based cohort study after adjustment for socioeconomic- and lifestyle-related CHD risk factors not commonly included in genetic association studies. Using the population-based Cohort of Norway (CONOR), a nested case-cohort study was set up and DNA from 2,953 subjects (829 cases and 2,124 non-cases) were genotyped. The association with fatal CHD was estimated for four SNPs, three from locus 1p13 and one from locus 9p21. Multivariable Cox regression was used to estimate unstratified and gender-stratified hazard ratios while adjusting for major CHD risk factors. The associations between three SNPs from locus 1p13 and non-HDL cholesterol levels were also estimated. Men homozygous for the risk alleles on rs1333049 (9p21) and rs14000 (1p13) were found to have significantly increased hazard ratios in crude and adjusted models, and the hazard ratios remained statistically significant when both genders were analyzed together. Adjustment for additional socioeconomic- and lifestyle-related CHD risk factors influenced the association estimates only slightly. No significant associations were observed between the other two SNPs in loci 1p13 (rs599839 and rs646776) and CHD mortality in either gender. Both rs599839 and rs646776 showed significant, gradual increases in non-HDL cholesterol levels with increasing number of risk alleles. This study confirms the association between 9p21 (rs1333049) and fatal CHD in a Norwegian population-based cohort. The effect was not influenced by several socioeconomic- and lifestyle-related risk factors. Our results show that 1p13 (rs14000) may also be associated with fatal CHD. SNPs at 1p13 (rs599839 and rs646776) were associated with non-HDL cholesterol levels.


Culturally adapted motivational interviewing's effects on drinking in response to immigration and acculturation stressors among Latinx adults with heavy drinking problems.
Culturally adapted motivational interviewing (CAMI) is a form of motivational interviewing that was adapted to address immigration- and acculturation-related stressors among Latinx adults who met criteria for hazardous drinking. This study hypothesized that (1) receiving CAMI was associated with reduced immigration/acculturation stress and related drinking and that (2) these associations differed by participants' acculturation and perceived discrimination levels. This study employed a single group pre-post study design using data from a randomized controlled trial. Participants were Latinx adults who received CAMI (N = 149). The study assessed immigration/acculturation stress with the Measure of Immigration and Acculturation Stressors (MIAS) and measured related drinking with the Measure of Drinking Related to Immigration and Acculturation Stressors (MDRIAS). The study team conducted linear mixed modeling for repeated measures to examine outcome changes between the baseline and the 6-month and 12-month follow-ups and moderation effects. Compared to baseline, the study found significant decreases in the total MIAS and MDRIAS scores and subscale scores at 6- and 12-month follow-ups. Moderation analysis results showed that lower acculturation levels and higher levels of perceived discrimination were significantly associated with larger decreases at follow-up in total MIAS and MDRIAS scores and several subscale scores. Findings provide preliminary support for CAMI's efficacy in reducing immigration and acculturation stress and related drinking among Latinx adults with heavy drinking problems. The study observed more improvements among the less acculturated and more discriminated participants. Larger studies with more rigorous designs are needed.


UGDAS: Unsupervised graph-network based denoiser for abstractive summarization in biomedical domain.
Abstractive summarization models can generate summary auto-regressively, but the quality is often impacted by the noise in the text. Learning cross-sentence relations is a crucial step in this task and the graph-based network is more effective to capture the sentence relationship. Moreover, knowledge is very important to distinguish the noise of the text in special domain. A novel model structure called UGDAS is proposed in this paper, which combines a sentence-level denoiser based on an unsupervised graph-network and an auto-regressive generator. It utilizes domain knowledge and sentence position information to denoise the original text and further improve the quality of generated summaries. We use the recently-introduced dataset CORD-19 (COVID-19 Open Research Dataset) on text summarization task, which contains large-scale data on coronaviruses. The experimental results show that our model achieves the SOTA (state-of-the-art) result on CORD-19 dataset and outperforms the related baseline models on the PubMed Abstract dataset.


Prediction of axial length on the basis of vitreous body length and lens thickness: retrospective echobiometric study.
To examine the predictability of axial length measurement when lens thickness and vitreous body length are known. Center of Ophthalmology, University of Cologne, Cologne, Germany. This study comprised 227 patients with a mean age of 70.01 years +/- 12.47 (SD). None of the eyes examined had a history of surgery or trauma. Patients with systemic disease were excluded from the study. Before cataract surgery, the length of the vitreous body and thickness of the lens were measured and the correlation between these data and the axial length was evaluated. Two ultrasonic devices were used for biometric measurements: the BMS 811 Biometric System (Grieshaber) and the Cooper Vision Ultrascan Digital A+B-Scan 2000. The correlations between the axial length and vitreous body length and the lens thickness and vitreous body length were analyzed using multiple linear regression. The BMS 811 provided the best prediction of axial length based on vitreous body length. Considering sex but not age significantly improved the model fit. With the BMS 811, the following formula was developed to predict axial length: Axial length (mm) = 7.129 mm + 0.095 mm x sex (female = 0, male = 1) + 1.040 x vitreous body length (mm). An approximate 95% prediction limit may be calculated by the following formula: Axial length (mm) +/- 2 x 0.413 mm. This study yielded an easy-to-use formula for predicting the axial length using the vitreous body length and the patient's sex. The remaining error in prediction is likely to be the result of patient heterogeneity in age, ocular globe size, and lens thickness (cataract formation). Good prediction of the axial length is important to refractive outcomes to distinguish corneal myopia from axial length myopia to choose grafts and the opening size in penetrating keratoplasty. Further studies to detect a clinically relevant improvement in such outcomes are required to assess the utility of the prediction formula.


Study of the formation of soluble complexes of sodium caseinate and xanthan in solution.
The main objective of this work was to determinate the optimum conditions for the formation of soluble complexes between sodium caseinate and xanthan in solution at neutral pH, in the presence of the NaCl. The study of the influence of the concentrations of these three substances showed that salt was the most influent factor. It worsens the thermodynamic incompatibility of the two biopolymers in solution, when they are present at large amounts. However, it contributes to soluble complexes formation, when sodium caseinate concentration is below 5.5%. In this case, gels with enhanced rheological properties were obtained. Infrared spectroscopy confirmed that the complexes formation within these gels involves hydrophobic interactions. On the other hand, dynamic light scattering revealed that dilution cause their dissociation. These soluble complexes are promising ingredients to ensure new texturing properties.


Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis.
Blepharophimosis-ptosis-epicanthus inversus syndrome type I is an autosomal disorder caused by mutations in FOXL2 gene and associated with premature ovarian failure in women by a dominant inheritance. FOXL2 is a recently identified protein that belongs to forkhead family transcription factor, of which signaling pathways are still unknown. Here, we show that FOXL2 induces apoptosis in both Chinese hamster ovary cells and rat granulosa cells, and it interacts with DP103, a DEAD box-containing protein. Overexpression of DP103 itself did not affect cell viability while its coexpression with FOXL2 led to the potentiation of cell death. Our results present previously undiscovered functions of these proteins, an apoptotic activity of FOXL2 in the ovary and a modulating activity of DP103 by interacting with FOXL2.


Targeting gold at the end of the rainbow: surgical gamma probes in the 21st century.
Surgical gamma detection probes (GDPs) have become important in the surgical management of neoplastic disease in the past 20 years. Their history and radiophysics are discussed, with consideration of the overarching issue of tumor-to-background ratio (TBR). GDPs are currently most commonly used in sentinel node applications in a variety of tumors. Whether their role in clinical surgical practice can be extended to other applications will depend on the development of radiolabeled tumor marking agents which have much improved TBR, and parallel developments in oncology research which may overtake this technology.


B cell malignant lymphoma in a patient with progressive systemic sclerosis and Sjögren's syndrome. Report of a case and review of the literature.
We report a patient with progressive systemic sclerosis (PSS) and Sjogren's syndrome (SS) who developed B cell malignant lymphoma 11 and 10 years after the onset of signs of PSS and SS, respectively. As her lymphoma developed, autoantibodies such as rheumatoid factor and antinuclear antibody disappeared from the serum, the lupus erythematosus test yielded negative results and her immunoglobulin levels declined. A good response to chemotherapy was obtained but she died of acute interstitial pneumonitis. Postmortem examination revealed marked diffuse interstitial fibrosis of the lungs.


Quantitative Validation of the Correlation Between Optimized Pyramidal Tract Delineation After Brain Shift Compensation and Direct Electrical Subcortical Stimulation During Brain Tumor Surgery.
It remains unclear whether tractography of pyramidal tracts is correlated with the intraoperative direct electrical subcortical stimulation (DESS), and brain shift further complicates the issue. The objective of this research is to quantitatively verify the correlation between optimized tractography (OT) of pyramidal tracts after brain shift compensation and DESS during brain tumor surgery. OT was performed for 20 patients with lesions in proximity to the pyramidal tracts based on preoperative diffusion-weighted magnetic resonance imaging. During surgery, tumor resection was guided by DESS. A total of 168 positive stimulation points and their corresponding stimulation intensity thresholds were recorded. Using the brain shift compensation algorithm based on hierarchical B-spline grids combined with a Gaussian resolution pyramid, we warped the preoperative pyramidal tract models and used receiver operating characteristic (ROC) curves to investigate the reliability of our brain shift compensation method based on anatomic landmarks. Additionally, the minimum distance between the DESS points and warped OT (wOT) model was measured and correlated with DESS intensity threshold. Brain shift compensation was achieved in all cases, and the area under the ROC curve was 0.96 in the registration accuracy analysis. The minimum distance between the DESS points and the wOT model was found to have a significantly high correlation with the DESS stimulation intensity threshold (r = 0.87, P < 0.001), with a linear regression coefficient of 0.96. Our OT method can provide comprehensive and accurate visualization of the pyramidal tracts for neurosurgical navigation and was quantitatively verified by intraoperative DESS after brain shift compensation.


Augmentation of incisor width with bonded composite resin: another look.
One of the most gratifying composite resin bonding procedures for patients and dentists alike is closure of unwanted and unsightly interdental spaces. Various methods of performing such bonding have been described. The most modern composite resins are strong, tooth-colored materials that can exactly simulate the appearance of normal tooth structure and reliably stay in place for many years. A method of augmenting the mesiodistal coronal dimension of anterior teeth without mechanical preparation of the enamel described.


[Elasticity and mechanism of action of bandage material in compression bandages].
Supportive bandages without elasticity (e.g. UNNA's-boats) aid the blood lift into the deep veins. Well-stretching bandages result in a more difficult return into the superficial veins. This may be demonstrated by photoplethysmography (PPG).


Deep potato - The hyperspectral imagery of potato cultivation with reference agronomic measurements dataset: Towards potato physiological features modeling.
The datasets provide hyperspectral imagery of potato fields with referencing agronomic measurements of several parameters. It contains also meteorological data collected on the place at the same time and some additional data on the variety of potatoes and the experiment. The experiment has been conducted in 2020 and two different potato varieties (Lady Claire and Markies) on the different soil profiles were planted and observed. During that time, on 4 different days, to provide a detailed picture of the experiment the hyperspectral imagery has been taken using a UAV and 150-band hyperspectral camera. The collected material has been later processed into 8 georeferenced ortophotomaps. To provide precise reference information that could be later used for modeling purpose the measurements of plants from each field has been performed. The registered data contains data on plant height, number of stems, stem fresh and dry mass, leaf fresh and dry mass, leaf assimilation area and LAI, number of tubers, tuber fresh and dry mass, starch content, RWC, chlorophyll a fluorescence index, the maximum quantum yield of PSII photochemistry, and the performance of electron flux.


Metabolic profiling of saponins in Medicago sativa and Medicago truncatula using HPLC coupled to an electrospray ion-trap mass spectrometer.
Triterpene saponins isolated from Medicago sativa (alfalfa) and Medicago truncatula roots were separated, profiled and identified using an optimized, reversed-phase HPLC with on-line photodiode array detection and electrospray ionization mass spectrometry method (HPLC/PDA/ESI/MS). ESI source polarity and solvent conditions were compared. The effects of these parameters on mass spectral attributes were determined. Ion structures were confirmed using tandem mass spectrometry (MS/MS). Fifteen saponins were identified in alfalfa (cultivars Apollo, Radius, and Kleszczewska) based upon negative-ion HPLC/PDA/ESI/MS, HPLC/PDA/ESI/MS/MS and literature data. In addition, the identification of two new malonated saponins in alfalfa are proposed. Negative-ion HPLC/PDA/ESI/MS and HPLC/PDA/ESI/MS/MS spectra were utilized along with HPLC retention times to profile and identify 27 saponins in M. truncatula (cultivar Jemalong, A17). M. truncatula yielded a much more complex mixture of saponins than observed for alfalfa. The authors are not aware of any previous reports identifying saponin glycosides in M. truncatula.


Meningiomas and the Polynesian population.
In Auckland Hospital, New Zealand there has been a perception for many years that the incidence of meningiomas was higher in Polynesians. It was also suspected these occurred at a younger age in Polynesians and were more likely to be multiple. The purpose of the present study was to confirm whether the Polynesian population does have a higher incidence of meningioma, review at what age they presented with meningioma and compare the outcome of treatment with Caucasians. A retrospective review was performed of 302 patients who had had a cranial meningioma excised in the 10 years between 1991 and 2001 at Auckland hospital. Age, sex, ethnicity, number of tumours, type, size, comorbidities, time to presentation and outcome at discharge and follow-up were recorded. Polynesians had a significantly higher incidence of meningiomas (P < 0.0001). In particular Polynesian women were significantly over represented. (P < 0.05). Polynesians were more likely to have two or more tumours (P < 0.02) and they presented at a significantly younger age (P < 0.0001). The tumours were also larger. (P = 0.0006). Despite this Polynesians did not have a worse outcome at discharge or at follow up (P > 0.1) nor did they have a higher incidence of comorbidites, perhaps reflected by their younger age. There is a higher incidence of meningiomas in the Polynesian population, particularly young Polynesian women. The tumours are more likely to be multiple and larger in Polynesians. The present study confirms a predisposition to meningioma in New Zealand Polynesians and should lead to further investigation into whether this is genetic (likely chromosome 22) or hormonal possibly mediated by insulin-like growth factor-1.


Distinguishing dural sinus thrombosis from benign intracranial hypertension.
Dural sinus thrombosis (DST) is a life threatening illness and is often overlooked but it must be considered in the differential diagnosis of a patient presenting with a significant headache. DST presents similarly to benign intracranial hypertension (BIH) with intracranial hypertension and headache. A case of a 23 year old woman with DST is described that was initially diagnosed as BIH. A Medline search to determine the examination of a patient with suspected BIH or DST yielded several articles on this topic but only two brief case reports in the emergency medicine literature. Any patient with suspected DST or BIH must have a confirmatory magnetic resonance imaging and magnetic resonance venography study. Treatment of DST seems to be effective, considerably different from BIH, and lack of treatment may lead to increased morbidity and mortality.


Depletion of awareness and double-simultaneous stimulation in split-brain man.
To examine depletion of awareness in six total split-brain patients response to two tactual stimuli applied at the same time was studied. Losses as well as errors in reporting location to one of the pair are present in all patients. This disorder is not seen in callosal patients in whom the splenium is preserved. The results are interpreted to follow the transection of a general consciousness circuit which lies towards the back of the brain.


Two-year Efficacy and Safety of Etanercept in Pediatric Patients with Extended Oligoarthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis.
The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample). There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported. Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.


Pharmacologic treatment of low back pain.
This article provides basic pharmacologic and behavioral principles and facts to simplify drug therapy for low back pain. It outlines basic protocols for symptom control while definitive treatments are beginning or healing occurs.


Effect of family-centered interventions for perinatal depression: an overview of systematic reviews.
This study aimed to evaluate and conclude the quality of critically systematic reviews (SRs) of the efficacy of family-centered interventions on perinatal depression. SRs of the efficacy of family-centered interventions on perinatal depression were systematically searched in nine databases. The retrieval period was from the inception of the database to December 31, 2022. In addition, two reviewers conducted an independent evaluation of the quality of reporting, bias risk, methodologies, and evidence using ROBIS (an instrument for evaluating the bias risk of SRs), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), AMSTAR 2 (an assessment tool for SRs), and grading of recommendations, assessment, development and evaluations (GRADE). A total of eight papers satisfied the inclusion criteria. In particular, AMSTAR 2 rated five SRs as extremely low quality and three SRs as low quality. ROBIS graded four out of eight SRs as "low risk." Regarding PRISMA, four of the eight SRs were rated over 50%. Based on the GRADE tool, two out of six SRs rated maternal depressive symptoms as "moderate;" one out of five SRs rated paternal depressive symptoms as "moderate;" one out of six SRs estimated family functioning as "moderate," and the other evidence was rated as "very low" or "low." Of the eight SRs, six (75%) reported that maternal depressive symptoms were significantly reduced, and two SRs (25%) were not reported. Family-centered interventions may improve maternal depressive symptoms and family function, but not paternal depressive symptoms. However, the quality of methodologies, evidence, reporting, and bias of risk in the included SRs of family-centered interventions for perinatal depression was not satisfactory. The above-mentioned demerits may negatively affect SRs and then cause inconsistent outcomes. Therefore, SRs with a low risk of bias, high-quality evidence, standard reporting, and strict methodology are necessary to provide evidence of the efficacy of family-centered interventions for perinatal depression.


[Risk and postoperative complications in abdominal surgery in elderly patients (author;s transl)].
1005 case histories of patients, older than 70 years, were studied retrospectively: 496 abdominal interventions (lethality - 29%), 509 extraabdominal interventions (lethality - 14%). In each patient 75 preoperative data are compared to 50 data of the intraoperative and postoperative period. There is a correlation between preoperative findings and postoperative complications and lethality. The main factors of risk are: Hb less than 10 g%, Creatinine greater than 1,5 mg%. The analysis implies the necessity of intensive preoperative therapy as well as the immediate correction of even slight post-operative deviations of the "norm".


Association of melanin pigmentation in the gingiva of children with parents who smoke.
The association between gingival pigmentation and active smoking has been established. This investigation is the first to address the relationship between gingival pigmentation in children and passive smoking. A case-control study was performed involving 59 nonsmoking children who were selected from patient records of a dental clinic in a rural town in Japan. The number of subjects was based on a power calculation. Two calibrated examiners independently observed labial gingiva via oral photographs. An interview determined that 61% of children had at least 1 smoking parent. Gingival pigmentation was observed in 71% to 78% of children. Interexaminer agreement was satisfactory (kappa = 0.73). Percentage of smoking parents was higher in children with gingival pigmentation (70-71%) than in those who lacked pigmentation (35%). Odds ratios of parental smoking adjusted by age and gender were 5.6 (95% confidence interval: 1.5-20.0) and 5.4 (1.4-21.2) for the 2 examiners. These findings suggest that excessive pigmentation in the gingiva of children is associated with passive smoking. The visible pigmentation effect in gingiva of children could be useful in terms of parental education.


Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlidemia.
Oxidized low-density lipoprotein plays an important role in the development of atherosclerosis. We evaluated the effect of two lipid-lowering drugs, bezafibrate and lovastatin, on the susceptibility of low-density lipoproteins for oxidation in vitro in 21 heart transplant recipients with hyperlipidemia. Patients were given the same diet for 3 months, and after that they were randomized to lovastatin or bezafibrate for a period of 8 weeks and then crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. The low-density lipoproteins of transplant recipients presents a shorter lag time than in control subjects (64+/-3 vs 80+/-4 minutes, respectively). This parameter increases after both bezafibrate and lovastatin treatment (83+/-5 and 80+/-4 minutes, respectively). Moreover, we did observe a negative correlation between insulinemia and the lag time of oxidation after bezafibrate treatment (r = -0.5014, P < .021) and between the polyunsaturated fatty acids/monounsaturated fatty acids ratio in low-density lipoprotein cholesterol esters and lag time after lovastatin treatment (r = -0.4631, P < .04). Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlipemia.


Body composition in young adults with inborn errors of protein metabolism--a pilot study.
The natural history of inborn errors of protein metabolism and the long-term effects of prescribed semisynthetic therapeutic diets are largely unknown. We assessed body composition, measuring body-fat mass and distribution, fat-free mass, total body protein, total body potassium, bone density and skeletal muscle mass, in young adults (age > 18 years; 6 female, 5 male) with inborn errors of protein metabolism maintained on long-term low-protein diets, compared with controls. Female patients were significantly shorter (159.4 cm vs 169.2 cm, p = 0.013) and had higher BMI (25.3 vs 22.0 kg/m2, p < 0.05), abdominal to gluteal circumference ratio (0.84 vs 0.73, p = 0.011), percentage body fat (42.3% vs 29.5%, p < 0.005) and ratio of central to peripheral body fat (1.15 vs 0.86, p < 0.05) than controls. Male patients had lower height-adjusted total body bone mineral content (0.9 vs 1.02 g/m2, p < 0.04) and skeletal muscle mass (31.1 vs 36.3 kg, p < 0.04) than controls. Compared with controls, patients'nitrogen index was significantly lower (0.91 vs 1.03, p < 0.01), consistent with lower total body protein. Potassium index was significantly higher (121.2% vs 110.4%, p < 0.03), consistent with higher body cell mass, or intracellular water. Documentation of body composition in larger patient series is important to elucidate whether these results reflect increased risks (hence opportunities for prevention) of bone disease, metabolic syndrome and cardiovascular disease in this population.


Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine.
We have investigated the nature of cannabinoid receptors in guinea-pig small intestine by establishing whether this tissue contains cannabinoid receptors with similar binding properties to those of brain CB1 receptors. The cannabinoids used were the CB1-selective antagonist SR141716A, the CB2-selective antagonist SR144528, the novel cannabinoid receptor ligand, 6'-azidohex-2'-yne-delta8-tetrahydrocannabinol (O-1184), and the agonists CP55940, which binds equally well to CB1 and CB2 receptors, and WIN55212-2, which shows marginal CB2 selectivity. [3H]-CP55940 (1 nM) underwent extensive specific binding both to forebrain membranes (76.3%) and to membranes obtained by sucrose density gradient fractionation of homogenates of myenteric plexus-longitudinal muscle of guinea-pig small intestine (65.2%). Its binding capacity (Bmax) was higher in forebrain (4281 fmol mg(-1)) than in intestinal membranes (2092 fmol mg(-1)). However, the corresponding KD values were not significantly different from each other (2.29 and 1.75 nM respectively). Nor did the Ki values for its displacement by CP55940, WIN55212-2, O-1184, SR141716A and SR144528 from forebrain membranes (0.87, 4.15, 2.85, 5.32 and 371.9 respectively) differ significantly from the corresponding Ki values determined in experiments with intestinal membranes (0.99, 5.03, 3.16, 4.95 and 361.5 nM respectively). The Bmax values of [3H]-CP55940 and [3H]-SR141716A in forebrain membranes did not differ significantly from each other (4281 and 5658 fmol mg(-1)) but were both greater than the Bmax of [3H]-WIN55212-2 (2032 fmol mg(-1)). O-1184 (10 or 100 nM) produced parallel dextral shifts in the log concentration-response curves of WIN55212-2 and CP55940 for inhibition of electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation, its KD values being 0.20 nM (against WIN55212-2) and 0.89 nM (against CP55940). We conclude that cannabinoid binding sites in guinea-pig small intestine closely resemble CB1 binding sites of guinea-pig brain and that 0-1184 behaves as a cannabinoid receptor antagonist in the guinea-pig myenteric plexus-longitudinal muscle preparation.


Macrophages Switch to an Osteo-Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model.
In mammals, osteoclasts differentiate from macrophages in the monocyte lineage. Although many factors driving osteoclast formation are known, the detailed processes underlying precursor recruitment, differentiation, and interaction of macrophages with other cell types involved in bone remodeling are poorly understood. Using live imaging in a transgenic medaka osteoporosis model, where ectopic osteoclasts are induced by RANKL expression, we show that a subset of macrophages is recruited to bone matrix to physically interact with bone-forming osteoblast progenitors. These macrophages subsequently differentiate into cathepsin K- (ctsk-) positive osteoclasts. One day later, other macrophages are recruited to clear dying osteoclasts from resorbed bone by phagocytosis. To better understand the molecular changes underlying these dynamic processes, we performed transcriptome profiling of activated macrophages upon RANKL induction. This revealed an upregulation of several bone-related transcripts. Besides osteoclast markers, we unexpectedly also found expression of osteoblast-promoting signals in activated macrophages, suggesting a possible non-cell autonomous role in osteogenesis. Finally, we show that macrophage differentiation into osteoclasts is dependent on inflammatory signals. Medaka deficient for TNFα or treated with the TNFα-inhibitor pentoxifylline exhibited impaired macrophage recruitment and osteoclast differentiation. These results show the involvement of inflammatory signals and the dynamics of a distinct subset of macrophages during osteoclast formation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Steroid protection in aging and age-associated diseases.
Neuroactive steroids are secretory products of peripheral endocrine glands that modulate a variety of brain functions. A close relationship between neuroactive steroid structure and function becomes most evident under pathological circumstances. On one side, overproduction of glucocorticoid and mineralocorticoid neuroactive steroids may be detrimental to the hippocampus, which is enriched in glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Thus, a dysfunction of the adrenocortical system in aging and age-associated diseases (diabetes, hypertension) is able to cause hippocampal damage. Whereas aging and uncontrolled diabetes show a predominant GR overdrive, a MR overdrive characterizes hypertensive animals. Some abnormalities commonly found in the hippocampus of aging, diabetic and hypertensive animals include decreased neurogenesis, astrogliosis and neuronal loss in the hilus of the dentate gyrus (DG). On the other side, and in contrast to adrenal gland-derived steroids, estrogens qualify as hippocampal neuroprotectants. Given to middle-age mice, estrogens stimulated proliferation and differentiation of newborn cells in the DG, decreased astrogliosis and increased hilar neuronal number. Similar estrogen effects were obtained in mice with streptozotocin-induced diabetes and in spontaneously hypertensive rats (SHR). The results suggest that in aging and age-associated diseases, adrenocortical steroid overdrive sensitizes the hippocampus to the pathological milieu imposed by a pre-existing degeneration or illness. In this setting, estradiol neuroprotection rescues hippocampal parameters previously altered by the pathological environment.


[Propensity score matching in SPSS].
To realize propensity score matching in PS Matching module of SPSS and interpret the analysis results. The R software and plug-in that could link with the corresponding versions of SPSS and propensity score matching package were installed. A PS matching module was added in the SPSS interface, and its use was demonstrated with test data. Score estimation and nearest neighbor matching was achieved with the PS matching module, and the results of qualitative and quantitative statistical description and evaluation were presented in the form of a graph matching. Propensity score matching can be accomplished conveniently using SPSS software.


Intraoperative evaluation of coronary bypass grafts by measuring myocardial blood flow using the electrolytic hydrogen clearance method.
The regional myocardial blood flow (MBF) was measured in 33 patients who underwent coronary bypass graft surgery in order to evaluate the efficiency of coronary bypass grafts in restoring MBF. MBF was measured by the electrolytic hydrogen clearance method during the coronary bypass surgery. The mean prebypass MBF was 161 +/- 19, 162 +/- 12, 80 +/- 12, 43 +/- 14, 104 +/- 18 ml/min/100 g in segments supplied by the left anterior descending coronary artery (LAD) showing less than or equal to 50 per cent, 75 per cent, 90 per cent, 99 per cent, and 100 per cent stenosis with collaterals, respectively. After bypass grafting of the LAD, the mean MBF increased from 70 +/- 13 and 126 +/- 12 ml/min/100 g to 133 +/- 14 and 163 +/- 9 ml/min/100 g in the segments with and without infarction, respectively. The mean postbypass MBF was 149 +/- 10 and 152 +/- 14 ml/min/100 g in the segments supplied by the LAD bypassed with saphenous vein grafts and mammary artery grafts, respectively. Postbypass MBF was dependent upon the magnitude of myocardial infarction. Measurement of MBF by the electrolytic hydrogen clearance method made it possible to quantitatively evaluate myocardial perfusion at the time of operation. It also provided direct information about the effectiveness of myocardial revascularization.


Inductive reasoning and implicit memory: evidence from intact and impaired memory systems.
In this study, we modified a classic problem solving task, number series completion, in order to explore the contribution of implicit memory to inductive reasoning. Participants were required to complete number series sharing the same underlying algorithm (e.g., +2), differing in both constituent elements (e.g., 2468 versus 57911) and correct answers (e.g., 10 versus 13). In Experiment 1, reliable priming effects emerged, whether primes and targets were separated by four or ten fillers. Experiment 2 provided direct evidence that the observed facilitation arises at central stages of problem solving, namely the identification of the algorithm and its subsequent extrapolation. The observation of analogous priming effects in a severely amnesic patient strongly supports the hypothesis that the facilitation in number series completion was largely determined by implicit memory processes. These findings demonstrate that the influence of implicit processes extends to higher level cognitive domain such as induction reasoning.


Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells.
Human A3 adenosine receptor (A3AR) agonists showed the anti-tumor activity in various in vitro and in vivo studies. The present study investigates the anti-proliferative effect of a novel adenosine analog 2-chloro-N6-(3-iodobenzyl)-4'-thioadenosine-5'-N-methyluronamide (thio-Cl-IB-MECA) in A549 human lung cancer cells. Thio-Cl-IB-MECA induced arrest of cell cycle progression in G0/G1 phase at lower concentrations (up to 20 microM) and apoptotic cell death at a higher concentration (80 microM), which were manifested by down-regulation of cyclin D1, c-myc, and CDK4, activation of caspase-3 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The activation of Akt-mediated signaling was also inhibited by treatment with thio-Cl-IB-MECA. These data might suggest the potential therapeutic value of an adenosine analog in the treatment of human lung cancer.


Why are people getting tested? Self-reported reasons for seeking voluntary counseling and testing at a clinic in Chennai, India.
VCT has been shown to be an important HIV risk reduction strategy; however, little is known about who attends VCT or why people seek VCT. A retrospective analysis was performed on charts of 6330 clients who attended VCT between 1994 and 2002 at Y.R. Gaitonde Centre for AIDS Research and Education, a non-governmental organization in Chennai, Tamil Nadu, India. Most clients reported more than one reason for attending VCT, and the most commonly reported reasons were risk behavior, having symptoms, having a current HIV-positive partner, and reconfirming a previous positive HIV test. Reasons varied by gender and over time, and the likelihood of testing positive for HIV varied by reason reported. Understanding why people seek VCT informs an understanding of knowledge and attitudes about HIV and HIV testing, which has implications for the development of education, outreach and other HIV prevention services.


Mammographic accuracy and patient age: a study of 297 patients undergoing breast biopsy.
This study was undertaken to compare the diagnostic accuracy of mammography in patients under 50 years with that of patients over 50, and with further subdivisions under 35 and 65 years. A retrospective review of the mammograms of 297 sequential patients undergoing mammography prior to surgical breast biopsy at the Breast Unit, Royal Marsden Hospital, London from 1988-1991 was performed. The films were reviewed blind by a single radiologist and correlated with histological findings at biopsy. The sensitivity and specificity of mammography compared with histology in four age-groups was assessed. There were 144 patients in the under-50 age group (< 35 years = 20, 35-49 years = 124), and 153 patients aged over 50 (50-64 years = 96, > 65 years = 57). Of all patients with histologically malignant biopsies 79% of the under-50s and 76% of the over-50s were diagnosed mammographically. Sensitivity of mammography was therefore 3% greater in the under-50 age-group (95% confidence interval (CI): +16% to -10%). Of patients who had benign biopsies, 76% of the under-50s and 75% of the over-50s were correctly diagnosed by mammography. Mammographic specificity was therefore 1% greater in the over-50 age-group (95% confidence interval: +15% to -14%). Accuracy of mammography was also comparable in the four subdivided age-groups. The results suggest that in patients requiring breast biopsy, contemporary mammography is similar in accuracy in the younger patient when compared to the older post-menopausal patient.


APC/Cdh E3 ubiquitin ligase in the pathophysiology of Alzheimer׳s disease.
The anaphase-promoting complex APC/C is a E3 ligase. It is regulates important functions in neural cells. Its inactivation and accumulation of its substrates has been related with neurodegenerative diseases. Glutaminase is an important target of APC/C-Cdh1 in primary neurons. It catalyzes the conversion of glutamine into glutamate. When cdh1 decreases due to incubation with Aβ, glutaminase concentration increases as does cyclin B1, a known target of the ubiquitin ligase that is involved in the pathophysiology of Alzheimer's disease (AD). The same treatment causes a high increase of glutamate levels in the supernatant of neurons in culture, which subsequently leads to an increase of Ca(2) inside the cells. The increase of glutamate due to the Aβ treatment can be partially reversed by a glutaminase inhibitor. This result suggests that the APC/C-Cdh1 signaling way is involved in the glutamate increase after the treatment with Aβ. Moreover, high levels of glutamate have been observed to further decrease cdh1 levels what also leads to an accumulation of gls. These results lead us to propose that neurons might enter into a positive feedback loop of glutamate production due to a lack of APC/C-Cdh1 signaling. This signaling pathway reveals a new mechanism to cause excitotoxicity in neurons, which could be relevant in AD.


Socioeconomic status influences bystander CPR and survival rates for out-of-hospital cardiac arrest victims.
While lower socioeconomic status is associated with lower level of education and increased incidence of cardiovascular diseases, the impact of socioeconomic status on out-of-hospital cardiac arrest outcomes is unclear. We used residential property values as a proxy for socioeconomic status to determine if there was an association with: (1) bystander CPR rates and (2) survival to hospital discharge for out-of-hospital cardiac arrest. We performed a secondary data analysis of cardiac arrest cases prospectively collected as part of the Ontario Prehospital Advanced Life Support study, conducted in 20 cities with ALS and BLS-D paramedics. We measured patient and system characteristics for cardiac arrests of cardiac origin, not witnessed by EMS, occurring in a single residential dwelling. We obtained property values from the Municipal Property Assessment Corporation. Analyses included descriptive statistics with 95% CIs and stepwise logistic regression. Three thousand six hundred cardiac arrest cases met our inclusion criteria between 1 January 1995 and 31 December 1999. Patient characteristics were: mean age 69.2, male 67.8%, witnessed 44.7%, bystander CPR 13.2%, VF/VT 33.8%, time to vehicle stop 5:36min:s, return of spontaneous circulation 12.7%, and survival 2.7%. Median property value was $184,000 (range $25,500-2,494,000). For each $100,000 increment in property value, the likelihood of receiving bystander CPR increased (OR=1.07; 95% CI 1.01-1.14; p=0.03) and survival decreased (OR=0.77; 95% CI 0.61-0.97; p=0.03). This is the largest study showing an association between socioeconomic status and survival, and the first study showing an association with bystander CPR. Our findings suggest targeting CPR training among lower socioeconomic groups.


Differentially expressed alternatively spliced genes in skeletal muscle from cancer patients with cachexia.
Alternative splicing (AS) is a post-transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms contribute to various cancers and muscle-related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in cancer cachexia (CC) remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome-wide scale and (ii) to identify differentially expressed alternatively spliced genes (DASGs) associated with CC. Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (n = 21, classified based on International consensus diagnostic framework for CC) and non-cachectic controls (n = 19, weight stable cancer patients). Human transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi-quantitative RT-PCR. We identified 8960 ASGs, of which 922 DASGs (772 up-regulated and 150 down-regulated) were identified at ≥1.4 fold-change and P < 0.05. Representative DASGs validated by semi-quantitative RT-PCR confirmed the primary findings from the human transcriptome arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination, and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters. Overall, we have, for the first time, conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts.


The evolving use of serum free light chain assays in haematology.
Over the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2-4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100-150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non-secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non-secretory and oligo-secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of lambda and kappa free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.


Interferon-alpha improves docetaxel antitumoral and antimetastatic efficiency in Lewis lung carcinoma bearing mice.
Interferon-alpha (IFN-α) was shown to reduce P-glycoprotein (P-gp) expression and activity in several tissues. The purpose of this study was to evaluate the impact of IFN-α pretreatment on the antitumoral and antimetastatic, Docetaxel (DTX, P-gp substrate), on Lewis Lung Cancer (3LL) bearing mice and to correlate it to DTX pharmacokinetics. Six groups of C57/Bl6 mice received subcutaneous (s.c.) 2.10(6) 3LL cells, then IFN-α 4MIU/kg for 7days, then received or did not receive i.v. or oral DTX (30mg/kg). Pharmacokinetic studies were done on a part of the mice: DTX concentrations were assessed in plasma and tumors, where AUC were estimated with the Bailer method, and half-lives and MRT were determined with a non-compartmental analysis. Tumor growth was assessed more than 21days: animals were then sacrificed and lung metastases number was counted. Kaplan-Meier analysis was made to analyze survival data during the survey period. DTX i.v. associated with IFN-α significantly improved mouse survival (19.6±0.6days vs. 17.1±0.8days for control mice, p=0.047) with greater antimetastatic effects (87.5% reduction in the number of metastases compared to control mice). The effect on tumor growth was not modified within the IFN-α/DTX i.v. treated groups when compared to mice receiving DTX i.v. alone. The pharmacokinetic analysis showed an increase of DTX concentrations in tumors at 30min after DTX i.v. administration and an increase in the oral bioavailability of orally given DTX following an IFN-α treatment. Our study established that IFN-α increases DTX uptake in tumors, improves its antitumoral efficiency and improves animals' survival.


Inhibitors of mitochondrial function prevent senescence in the ascomycete Podosprora anserina.
The onset of senescence, i.e. decrease of growth rate followed by cellular death, is prevented when inhibitors of mitochondrial function (ethidium-bromide, streptomycin, tiamulin) are present in the culture medium. If mycelia are transferred to a medium not containing one of these substances, senescence occurs after the usual time interval (30 d at 26 degrees C). Inhibitors of cytoplasmic protein synthesis such as emetine and cycloheximide have no effect in preventing senescence.


[Oral leukoplakia in manifest squamous epithelial carcinoma. A clinical prospective study of 101 patients].
The Uppsala-definition of leukoplakia has recently redefined oral leukoplakia. Based on this definition, the aim of our study was to reevaluate the prevalence of oral leukoplakia in patients with histologically proven primary oral cancer. A total of 101 in-patients in four tumor centers in Berlin were interviewed and clinically examined just prior to surgery of an oral squamous cell carcinoma (OSCC). The prevalence of leukoplakia immediately adjacent to the carcinoma was 15.8%. Additional leukoplakias without relation to the carcinoma were found in 4% of the patients. There were no significant differences in age- or sex-distribution, history of tobacco habits or diet between patients with or without leukoplakia. T1 carcinomas were found in 62.5% of patients with, and 24.4% of patients without associated leukoplakia, whereas a balanced distribution was found for the pre-operative staging of the tumor. The prevalence of oral leukoplakia in patients with OSCC was low, compared to retrospective studies. The presence or absence of leukoplakia indicated no influence on the prognosis of the tumor, except of tumor size. The results emphasize that most OSCC develop from healthy appearing oral mucosa.


Prenatal features, associated co-morbidities and clinical course of agenesis of the ductus venosus in the current era.
Agenesis of the ductus venosus (ADV) has been associated with additional anomalies in up to 83% of cases. We sought to investigate characteristics, co-morbidities and outcomes of ADV in the current era. We hypothesized that rates of cardiac and non-cardiac diagnoses and survival would be higher, due to advances in genetic testing, prenatal diagnosis and surveillance. A retrospective series of cases diagnosed at our institution from 2007 to 2018 were identified by searching our database. Cardiac and obstetric charts were reviewed for cardiac and extra-cardiac anomalies, genetic results and outcomes. Fourteen cases were diagnosed at a mean gestational age of 23.9 weeks (range 13-33). All had associated genetic, cardiac or extra-cardiac anomalies. Eight (57%) had cardiac anomalies and one other developed cardiomyopathy by 6 months. Extra-cardiac anomalies were present in 93% (13/14) and genetic diagnoses made in 75% (6/8) of those tested. Cardiac output Z-scores were >2 in 60% (6/10) prior to delivery. Two had hydrops, there was one intra-uterine death, 13 live-births and two neonatal deaths. Our cohort had more associated diagnoses and a lower mortality than previously reported. In our experience, high output occurs frequently, however with a relatively low risk of hydrops and intrauterine death.


Role of Prostaglandin D2 and DP1 Receptor on Japanese Cedar Pollen-Induced Allergic Rhinitis in Mice.
Although we previously demonstrated the contribution of the DP1receptor in nasal obstruction using animals sensitized with ovalbumin in the presence of adjuvant, the contribution of the DP1receptor in sneezing is unclear. Here, we developed a mouse model of Japanese cedar (JC:Cryptomeria japonica) pollinosis to evaluate the symptoms of sneezing. To achieve this, we used JC pollen crude extract in the absence of adjuvant to sensitize mice to develop a model closer to the pathophysiology of human JC pollinosis. The immunologic and pharmacologic features of this model are highly similar to those observed in JC pollinosis in humans. Using this model, we found that DP1receptor antagonists suppressed JC pollen extract-induced sneezing and that a DP1receptor agonist induced sneezing. Moreover, JC pollen extract-induced sneezing was diminished in DP1receptor knockout mice. In conclusion, we developed a novel mouse model of allergic rhinitis that closely mimics human JC pollinosis. A strong contribution of DP1receptor signaling to sneezing was demonstrated using this model, suggesting that DP1receptor antagonists could suppress sneezing and nasal obstruction, and therefore these agents could be a new therapeutic option for allergic rhinitis.


Cholesterol can modulate mitochondrial aquaporin-8 expression in human hepatic cells.
Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under such conditions, mtAQP8 mRNA and protein expressions were significantly reduced. In contrast, cholesterol depletion using mβCD alone increased SREBP-1 and 2 activation and upregulated HMGCR and mtAQP8 mRNA and protein expressions. The results suggest that cholesterol can regulate transcriptionally human hepatocyte mtAQP8 expression likely via SREBPs. The functional implications of our findings are discussed. © 2017 IUBMB Life, 69(5):341-346, 2017.


The effect of fenoldopam on the blood pressure of the rat.
1. Fenoldopam mesylate, a benzazepine derivative, is a D1 receptor agonist that lowers blood pressure through vasodilation of renal, mesenteric, coronary and cerebral vascular beds. 2. Experiments were performed in rats, and mean carotid blood pressure and heart rate were registered. Two series of experiments were performed: (1) fenoldopam as control group and (2) fenoldopam after pretreatment with one of the following drugs: the D1 antagonist SCH 23390, the D2 antagonist sulpiride, the selective beta1-adrenergic antagonist atenolol, the selective beta2-adrenergic antagonist ICI 118.551, the nonselective beta-adrenergic antagonist propranolol and the neurotoxin that destroys catecholaminergic nerve terminals 6-hydroxydopamine (6-OH-DA). 3. Fenoldopam produced a dose-dependent hypotensive effect that was not modified by pretreatment of the rat with atenolol or propranolol; however, ICI 118.551 produced a significant reduction of the hypotensive response induced by fenoldopam. 4. Pretreatment of the animals with SCH 23390 produced a significant dose-related reversal of the rat blood pressure reduction induced by low doses of fenoldopam. Sulpiride produced a result similar to that induced by pretreatment with SCH 23390. 5. The pretreatment of the animals with 6-OH-DA surprisingly attenuated the response induced by fenoldopam and produced only a significant reversal of the reduction of mean blood pressure induced with the lower dose of fenoldopam. 6. The findings obtained in the present work do not provide further evidence of direct participation of beta2-adrenergic receptors on the mechanism of action of fenoldopam. Its action seems to be mainly due to activation of D1 cardiovascular receptors.


Localization of endogenous galactoside-binding lectin during morphogenesis of Xenopus laevis.
A monoclonal antibody has been produced against Xenopus laevis galactoside-binding neural-crest-stage lectin. This antibody inhibits lectin-mediated hemagglutination. Using this antibody in conjunction with immunohistochemical techniques, lectin deposition has been studied in embryos and tadpoles at different stages of morphogenesis, from initial neural crest migration, up to the formation of a swimming tadpole. Lectin levels change during development in different regions of the embryo and tadpole, decreasing in migratory cells, and increasing in sites where cells become more adhesive to one another. The results suggest that galactoside-binding lectins may be an important class of cellular adhesion molecules during these stages of development.


Preparation and characterization of long chain amino acid and peptide vesicle membranes.
Four amino acid dicarboxylic amphiphiles which contain cysteine or homocysteine were synthesized. Each forms synthetic bilayer membranes upon hydration. Extensive sonication above the lipid phase transition temperature, 61 to 82 degrees C, produced 1000 A diameter vesicles. Treatment of the vesicles with water-soluble carbodiimides during and after sonication induced oligopeptide formation at the vesicle surface with retention of vesicle size and shape. Size exclusion chromatography indicates the products are predominantly di- to decapeptides. The permeability characteristics of the amino acid and peptide vesicles to [3H]glucose and 6-carboxyfluorescein are reported. The amino acid vesicles are among the least permeable nonpolymerized bilayer vesicles described in the literature to date. Formation of the peptide vesicles increases the membrane permeability, whereas in other polymerizable lipid vesicles the permeability decreases upon polymerization. The amino acid vesicles can be immobilized on Sephadex beads by reaction with carbodiimide. The impermeability, biodegradability, and ease of immobilization make this class of vesicles attractive materials for the encapsulation of reagents.


Affirming Care for Sexual and Gender Minority Prostate Cancer Survivors: Results from an Online Training.
Sexual and gender minority people have unique, unaddressed healthcare needs following prostate cancer. The research team along with a group of established subject matter experts developed a training and companion materials for healthcare professionals to address this need. Post-assessment evaluation was reported in frequencies and percentages by combining results from learners who attended an original, live web-based training and learners who completed the same training on-demand via a Learning Management System. Learners from both the live and archived training reported that the training increased their knowledge to effectively work with sexual and gender minority prostate cancer survivors. Learners also reported gaining new resources and strategies they could apply to their work. Results indicate the training fills an educational gap for healthcare professionals and supports the need for additional training of healthcare professionals focused on the healthcare needs of SGM cancer survivors.


Utility of rodent models for evaluating protein allergenicity.
Animal models are needed to assess novel proteins produced through biotechnology for potential dietary allergenicity. The exact characteristics that give certain foods allergenic potential are unclear, but must include both the potential to sensitize (induce IgE) as well as the capacity to avoid induction of oral tolerance (specific inhibition of IgE production). EPA has developed two complementary mouse models; one which distinguishes allergenic from non-allergenic food extracts using oral sensitization with adjuvant (cholera toxin) and another which further distinguishes highly potent allergens following oral administration without adjuvant based on the development (or not) of tolerance. For the foods tested thus far (roasted or raw peanut, Brazil nut, egg white, turkey, and spinach), the ability to sensitize and/or tolerize in these models are consistent with observed allergenicity as well as persistence and severity among allergens. Additionally, in vitro pepsin-resistance analysis of these food extracts suggests an association between sensitization capacity and proteins which are stable to gastric digestion. A subcutaneous exposure model did not distinguish allergenic from non-allergenic foods and does not appear useful for assessing potential allergenicity.


[How is iron prescribed in French ICUs: a practice survey].
To evaluate the practice concerning the iron prescription by French intensivists. Survey during an intensive care-national congress. Interviewed practitioners were separated in two groups (prescribing [P] iron once time or more per week; or not [NP] less than one time per month). Iron-treatments (iv or oral) efficacy and tolerance were quoted from 1 to 10. All the 128 interviewed intensivists (73% male; mean age 36+/-8 years) considered having anaemic patients and 94% considered having patients with iron deficiency. For 72% of them, the iron deficiency was judged frequent (concerning >10% of their patients) and 25% were P. Intravenous iron, oral iron or both were used by, respectively, 20, 35 and 44% of the interviewed intensivists. Intravenous iron was considered more efficient (7+/-2 versus 6+/-2; p<0.001) and better tolerated (7+/-2 versus 6+/-2; p<0.001) than oral iron. There was no demographic difference between P and NP. P answered more often having patients with iron deficiency (p=0.04), but they did not perform biological tests for diagnosis of iron deficiency more often and did not consider iron-treatment efficacy or tolerance higher than NP. Intensive-care anaemia and iron deficiency were considered to be frequent and iron treatments to be efficient and quite well tolerated. But only 25% of the interviewed intensivists were frequent-iron prescribers. This survey underscore that iron prescription in ICU seems to rely more on clinical feeling than on strong evidence: it's time to investigate!


Neurotic depression: a diagnosis based on preexisting characteristics.
A neurotic depression is a depression in an emotionally unstable person. Secondary depressions to major personality disorders, neuroses, and drug use disorders fit the above definition. Likewise, primary depressions with a family history of alcohol (depression spectrum disease) are characterized by a long history of stormy life problems and, therefore, would fit the definition. Using these two preexisting characteristics, we examined a group of 401 neurotic depressives and compared them to 536 nonneurotic (endogenous) depressives. The neurotic depressives were younger and the neurotic patients had made more previous suicide attempts. They were less likely to show memory deficits or delusions and less likely to show symptom criteria of melancholia. They were more likely to have suicide thoughts at index. Treatment was more effective in the nonneurotic patients and such patients made fewer suicide attempts in follow-up. These differences confirm the validity of the distinction between neurotic and nonneurotic depression.


DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core with terminal carbamate and ester groups.
The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righthand side with ten carbamate terminal groups and one ester function G(v1) have been recorded. The IR and Raman spectra of the zero generation dendron G(v0) and first generation dendrimer G(1) with the same core and terminal groups were also examined. The structural optimization and normal mode analysis were performed for dendron G(v1) on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that G(v1) has a concave lens structure with planar -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righhand side fragments and slightly non-planar cyclotriphosphazene core. The carbamate groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectrum of G(v1) dendron was interpreted by means of potential energy distributions. The strong band 1604 cm(-1) shows marked changes of the optical density in dependence of the carbamate, ester or azomethyne substituents in the aromatic ring. The frequencies of ν(N-H) and ν(C=O) bands in the IR spectra reveal the presence of the different types of H-bonds in the studied dendrimers.


Designing ultrathin film composite membranes: the impact of a gutter layer.
Industrial membranes comprised of a thin selective layer (<100 nm) requires a gutter layer (<100 nm) between the selective layer and the porous support to achieve high permeance for gas separation. The gutter layer materials must be carefully chosen to enhance overall membrane performance, i.e., high permeance and high selectivity. However, the experimental determination of the optimum gutter layer properties is very challenging. Herein we address this need using a three dimensional (3D) computational model to systematically determine the effects of the gutter layer thickness and permeability on membrane performance. A key finding is that the introduction of a gutter layer between the selective layer and porous support can enhance the overall permeance of the penetrant by up to an order of magnitude, but this gain is accompanied by an undesired decrease in selectivity. The analysis also shows for the first time that a maximum increase in permeance with negligible decrease in selectivity is realized when the thickness of the gutter layer is 1-2 times the pore radius. The modeling approach provides clear and practical guidelines for designing ultrathin multilayer composite membranes to achieve high permeance and selectivity for low-cost and energy-efficient molecular separations.


Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer.
Our study aimed to evaluate response rate (RR) to brain metastasis radiotherapy (RT), depending on the genomic status of non-small-cell lung cancer. We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis. A total of 16 patients (10.2%) harbored EGFR mutations (mEGFR) and 45 patients (28.7%) KRAS (mKRAS). In univariate analysis, RR was significantly higher for mEGFR compared with wild-type EGFR/KRAS (odds ratio [OR]: 4.96; p = 0.05) or mKRAS (OR: 1.81; p = 0.03). In multivariate analysis, KRAS G12V or G12C status was associated with both poor RR (OR: 0.1; p < 0.0001) and overall survival (OR: 3.41; p < 0.0001). mEGFR are associated with higher RR to brain RT than wild-type EGFR/RAS or mKRAS.


Vasoactive intestinal polypeptide-immunoreactive neurons in the main olfactory bulb of the hedgehog (Erinaceus europaeus).
Vasoactive intestinal polypeptide (VIP) immunoreactivity was localized by the indirect antibody enzyme method (PAP technique) in the main olfactory bulb of the hedgehog. Most VIP-immunoreactive cells were located in the glomerular layer and throughout the external plexiform layer. Fewer cells were observed in the granule cell layer. At the morphological level they exhibit the characteristics of periglomerular, external tufted, superficial short axon, horizontal and Van Gehuchten cells. It should be mentioned that another specific neuronal type was found in the inner third of the external plexiform layer, which is not described in other animals. These results revealed that a high number of intrinsic neuronal types of the olfactory bulb of the hedgehog display a strong VIP immunoreactivity.


New aspects of the epigenetic regulation of EMT related to pulmonary fibrosis.
Pulmonary fibrosis is a chronic and progressive fibrotic disease that results in impaired gas exchange, ventilation, and eventual death. The pro-fibrotic environment is instigated by various factors, leading to the transformation of epithelial cells into myofibroblasts and/or fibroblasts that trigger fibrosis. Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in the pathogenesis of pulmonary fibrosis. Epigenetic regulation of tissue-stromal crosstalk involving DNA methylation, histone modifications, non-coding RNA, and chromatin remodeling plays a key role in the control of EMT. The review investigates the epigenetic regulation of EMT and its significance in pulmonary fibrosis.


Evaluation of a year-long dispersion modelling of PM10 using the mesoscale model TAPM for Christchurch, New Zealand.
This paper examines the utility of The Air Pollution Model (TAPM; version 2) in simulating meteorology and dispersion of PM(10) for 1999 over the coastal city of Christchurch, New Zealand. Christchurch usually experiences severe degradation in air quality during austral winter. The formation of a nocturnal inversion layer and the emissions of particulate matter (PM(10)) mainly from solid fuel home heating appliances lead to severe smog episodes on an average of 30 nights during winter. The complex local topography surrounding the city in combination with influences from the urban areas can produce complicated boundary layer winds during quiescent weather. Simulated PM(10) data are used for construction of annual exposure maps for the urban areas in order to assess the health impact of air pollutants due to chronic exposure (presented in an accompanying paper). Meteorology and PM(10) dispersion results are statistically compared with the only permanent air pollution monitoring station available in order to evaluate the model's performance. Statistical measures such as the Index of Agreement (IOA) between modelled and measured data indicate that the model performs well. IOA is greater than 0.6 for meteorological variables, and various calculated skill scores place confidence in the model's performance. However, TAPM has a tendency to overestimate surface wind speed over urban areas during stagnant nocturnal conditions, resulting in quick flushing of pollutants.


Reflections on 'plant neurobiology'.
Plant neurobiology, a new and developing area in the plant sciences, is a meeting place for scientists concerned with exploring how plants perceive signs within their environment and convert them into internal electro-chemical ('plant neurobiological') signals. These signals, in turn, permit rapid modifications of physiology and development that help plants adjust to changes in their environment. The use of the epithet 'neurobiology' in the context of plant life has, however, led to misunderstanding about the aims, content, and scope of this topic. This difficulty is possibly due to the terminology used, since this is often unfamiliar in the context of plants. In the present article, the scope of plant neurobiology is explored and some of analogical and metaphorical aspects of the subject are discussed. One approach to reconciling possible problems of using the term 'plant neurobiology' and, at the same time, of analysing information transfer in plants and the developmental processes which are regulated thereby, is through Living Systems Theory (LST). This theory specifically directs attention to the means by which information is gathered and processed, and then dispersed throughout the hierarchy of organisational levels of the plant body. Attempts to identify the plant 'neural' structures point to the involvement of the vascular tissue - xylem and phloem - in conveying electrical impulses generated in zones of special sensitivity to receptive locations throughout the plant in response to mild stress. Vascular tissue therefore corresponds, at the level of organismic organisation, with the informational 'channel and net' subsystem of LST.


Classification of ecstasy tablets using trace metal analysis with the application of chemometric procedures and artificial neural network algorithms.
This work is concerned with an investigation into the practicalities of using ICP-MS data obtained from the analysis of ecstasy tablets to provide linkage information from seizure to seizure. The generated data was analysed using different statistical techniques, namely principal component analysis, Hierarchical clustering and artificial neural networks. The relative merits of these different techniques are discussed.


Comparative study of perceived pain and nociceptive flexion reflex in man.
The purpose of this study was to compare the amplitude of the flexion reflex of the biceps femoris muscle (BF) with the intensity of the painful sensation elicited by a nociceptive stimulation resulting from application of constant-current either on the sural nerve or on the skin in its distal receptive field. Experiments were carried out on 15 normal volunteers. It was observed that: (1) Stimulation of the sural nerve (either on or through the skin) elicits two different reflex responses in the BF: the first (RII) is of short latency, low threshold and corresponds to a tactile reflex. The second (RIII) is of longer latency and higher threshold, and corresponds to a nociceptive reflex. The threshold of RIII was found to be the threshold of a pain sensation. (2) Stimulation of the skin elicits only a late nociceptive (RIII) response in the BF. The threshold of this response was also found to be that of pain. (3) The threshold of both pain and RIII were found to be higher for sural nerve stimulation (10 mA) than for cutaneous stimulation (5 mA). It was suggested that the large diameter cutaneous fibers could have an inhibitory effect of both pain and the nociceptive reflex. This was supported by the results obtained during a selective ischemic block of the largest diameter fibers in the sural nerve, when a 10 mA stimulation was applied to the nerve. In this case, a decrease of the RII reflex was observed in BF, together with an increase of both RIII and pain sensation. Functional implications of these results are discussed.


The effect of treatment strategy on long-term follow-up results in patients with nonvalvular atrial fibrillation in Turkey: AFTER-2 subgroup analysis.
We performed a subanalysis of the data from the AFTER-2 registry. In our study, we aimed to compare the long-term follow-up results of nonvalvular atrial fibrillation (NVAF) patients in Turkey according to their treatment strategies. All consecutive patients older than 18 years of age who presented to cardiology outpatient clinics, had at least one AF attack and did not have rheumatic mitral valve stenosis or prosthetic heart valve disease were included in our prospective study. The patients were divided into two groups as rhythm control and rate control. Stroke, hospitalization and death rates were compared between the groups. A total of 2592 patients from 35 centers were included in the study. Of these patients, 628 (24.2%) were in the rhythm control group and 1964 (75.8%) in the rate control group. New-onset ischemic cerebrovascular disease or transient ischemic attack (CVD/TIA) was detected at a lower rate in the rhythm control group (3.2% vs. 6.2% p = 0.004). However, there was no significant difference in one-year and five-year mortality rates (9.6% versus 9.0%, p = 0.682 and 31.8% versus 28.6%, p = 0.116, respectively). Hospitalization were found to be significantly higher in patients with rhythm control group (18% vs. 13%, p = 0.002). It was found that rhythm control strategy is preferred in AF patients in Turkey. We found a lower rate of ischemic CVD/TIA in patients in the rhythm control group. Although no difference was observed in mortality rates, we found a higher rate of hospitalization in the rhythm control group.


Spontaneous closure of cerebral arteriovenous malformation demonstrated by angiography and computed tomography.
Spontaneous disappearance of a cerebral arteriovenous malformation, presumably secondary to thrombosis, was demonstrated in a young female patient by angiography and computed tomography 11 and 13 years respectively after the initial radiographic demonstration of the lesion.


Tumor length in elderly patients with esophageal squamous cell carcinoma: is it a prognostic factor?
Several researchers have determined the tumor length to be an important prognostic indictor of esophageal cancer (EC). However, controversy exists concerning the optimal cut-off points for tumor length to predict overall survival. The aim of this study was to determine the prognostic value of tumor length and propose the optimum cut-off point for tumor length in predicting survival difference in elderly patients with esophageal squamous cell carcinoma (ESCC). From January 2001 to December 2009, a retrospective analysis of 132 consecutive patients older than 70 years with ESCC was conducted. A receiver-operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cut-off point for tumor length. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. A ROC curve for survival prediction was plotted to verify the optimum cut-off point for tumor length, which was 4.0 cm. Patients with tumor length ≤ 4.0 cm had significantly better 5-year survival rate than patients with a tumor length >4.0 cm (60.7% versus 31.6%, P = 0.007). Multivariate analyses showed that tumor length (>4.0 cm versus ≤ 4.0 cm, P = 0.036), differentiation (poor versus well/moderate, P = 0.032), N staging (N1-3 versus N0, P = 0.018), and T grade (T3-4 versus T1-2, P = 0.002) were independent prognostic factors. Tumor length is a predictive factor for long-term survival in elderly patients with ESCC, especially in T3-4 grade or nodal-negative patients. We conclude that 4.0 cm may be the optimum cut-off point for tumor length in predicting survival in elderly patients with ESCC.


The behavioral effect of vasopressin in the ventral hippocampus is antagonized by an oxytocin receptor antagonist.
[Arg8]vasopressin improved long-term retrieval processes and relearning in a go-no go visual discrimination task when bilaterally microinjected at a dose of 25 pg/animal into the ventral hippocampus of mice, 10 min prior to the retention session. We had shown that this enhancing effect is antagonized by pretreatment with equal or lower doses (25 pg or 1 ng) of the vasopressin V1 receptor antagonist, (d(CH2)5Tyr(Me)-vasopressin). The present study was an attempt to determine whether the vasopressin V2 receptor antagonist or oxytocin receptor antagonist is as effective as the vasopressin V1 receptor antagonist to block the behavioral effect of vasopressin in the ventral hippocampus. We tested the effect of 25 pg of [d(CH2)5-D-Ile2,Ile4,Arg8]vasopressin, a vasopressin V2 receptor antagonist, and [d(CH2)5,Tyr(Me)2,Thr4,Tyr-NH9(2)]ornithine vasotocin, an oxytocin receptor antagonist, under the same experimental conditions as those used to test the effect of the vasopressin V1 receptor antagonist. The results showed that the vasopressin V2 receptor antagonist microinjected into the ventral hippocampus did not alter the enhancing effect of vasopressin on retrieval and relearning. In contrast, the oxytocin receptor antagonist blocked the vasopressin-enhancing effect on retention processes. We can conclude from the data that both vasopressin V1 receptors and oxytocin receptors seem to be involved in the enhancing effect of vasopressin on memory retention. In contrast, the vasopressin V2 receptors do not seem to be involved in the effect of the peptide.


N-{2-[4-(2-Hy-droxy-eth-yl)piperazin-1-yl]eth-yl}phthalimide.
In the title compound, C(16)H(21)N(3)O(3), the piperazine ring adopts a chair conformation, with its N-C bonds in pseudo-equatorial orientations. In the crystal, mol-ecules are linked by O-H⋯N hydrogen bonds, generating C(5) chains propagating in [101]. Weak aromatic π-π stacking inter-actions also occur [centroid-centroid separation = 3.899 (1) Å].


Prognostic implications of surgical specimen quality on the oncological outcomes of open and laparoscopic surgery in mid and low rectal cancer.
Determine differences in pathologic outcomes between laparoscopic (LAP) and open surgery (OPEN) for mid and low rectal cancer and its influence in long-term oncological outcomes. Retrospective case matched study at a tertiary institution. Adults with rectal cancer below 12 cm from the anal verge operated between January 2005 and September 2018 were included. Primary outcomes were quality of specimen, overall survival (OS), disease-free survival (DFS), and local recurrence (LR). The study included 311 patients, LAP = 108 (34.7%), OPEN = 203 (65,3%). A successful resection was accomplished in 81% of the LAP group and in 84.5% of the OPEN (p = 0.505). No differences in free distal margin (LAP = 100%, OPEN = 97.5%; p = 0.156) or circumferential resection margin (LAP = 95.2%, OPEN = 93.2%; p = 0.603) were observed. However, mesorectum quality was incomplete in 16.2% for LAP and in 8.1% for OPEN (p = 0.048). OS was 91.1% for LAP and 81.1% for OPEN (p = 0.360). DFS was 81.4% for LAP and 77.5% for OPEN (p = 0.923). Overall, LR was 2.3% without differences between groups. Laparoscopic approach could affect the quality of surgical specimen due to technical aspects. However, if principles of surgical oncology are respected, minor pathologic differences in the quality of the mesorectum may not influence on the long-term oncologic outcomes.


Volume fractions of DCE-MRI parameter as early predictor of histologic response in soft tissue sarcoma: A feasibility study.
To find early predictors of histologic response in soft tissue sarcoma through volume transfer constant (Ktrans) analysis based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). 11 Patients with soft tissue sarcoma of the lower extremity that underwent preoperative chemoradiotherapy followed by limb salvage surgery were included in this retrospective study. For each patient, DCE-MRI data sets were collected before and two weeks after therapy initiation, and histologic tumor cell necrosis rate (TCNR) was reported at surgery. The DCE-MRI volumes were aligned by registration. Then, the aligned volumes were used to obtain the Ktrans variation map. Accordingly, three sub-volumes (with increased, decreased or unchanged Ktrans) were defined and identified, and fractions of the sub-volumes, denoted as F+, F- and F0, respectively, were calculated. The predictive ability of volume fractions was determined by using area under a receiver operating characteristic curve (AUC). Linear regression analysis was performed to investigate the relationship between TCNR and volume fractions. In addition, the Ktrans values of the sub-volumes were compared. The AUC for F- (0.896) and F0 (0.833) were larger than that for change of tumor longest diameter ΔD (0.625) and the change of mean KtransΔKtrans¯ (0.792). Moreover, the regression results indicated that TCNR was directly proportional to F0 (R2=0.75, P=0.0003), while it was inversely proportional to F- (R2=0.77, P=0.0002). However, TCNR had relatively weak linear relationship with ΔKtrans¯ (R2=0.64, P=0.0018). Additionally, TCNR did not have linear relationship with DD (R2=0.16, P=0.1246). The volume fraction F- and F0 have potential as early predictors of soft tissue sarcoma histologic response.


Anal fistulas at St Mark's Hospital.
This paper presents the application of a classification of anal fistulas to an unselected consecutive series of 793 patients treated for this condition at St Mark's Hospital from 1968 to 1973 inclusive. The fistulas were divided into five categories on their anatomical relationships: superficial (16 per cent), intersphincteric (54 per cent), trans-sphincteric (21 per cent), suprasphincteric (3 per cent) and extrasphincteric (3 per cent), with the remaining cases multiple or unclassified (3 per cent). There was good correlation between the categories and presentation, physical signs and treatment of the fistulas. Two hundred and forty-nine patients had potentially difficult fistulas. Follow-up of these patients revealed healing of almost all the fistulas, but the functional results were less satisfactory (incontinence of loose stool in 17 per cent and of flatus in 25 per cent, soiling in 31 per cent).


A field study of the accuracy and reliability of a biometric iris recognition system.
The iris of the eye appears to satisfy the criteria for a good anatomical characteristic for use in a biometric system. The purpose of this study was to evaluate a biometric iris recognition system: Mobile-Eyes™. The enrollment, verification, and identification applications were evaluated in a field study for accuracy and reliability using both irises of 277 subjects. Independent variables included a wide range of subject demographics, ambient light, and ambient temperature. A sub-set of 35 subjects had alcohol-induced nystagmus. There were 2710 identification and verification attempts, which resulted in 1,501,340 and 5540 iris comparisons respectively. In this study, the system successfully enrolled all subjects on the first attempt. All 277 subjects were successfully verified and identified on the first day of enrollment. None of the current or prior eye conditions prevented enrollment, verification, or identification. All 35 subjects with alcohol-induced nystagmus were successfully verified and identified. There were no false verifications or false identifications. Two conditions were identified that potentially could circumvent the use of iris recognitions systems in general. The Mobile-Eyes™ iris recognition system exhibited accurate and reliable enrollment, verification, and identification applications in this study. It may have special applications in subjects with nystagmus.


Metabolic Sequelae: The Pancreatitis Zeitgeist of the 21st Century.
Holistic management of pancreatitis means that gastroenterologists in the 21st Century should think beyond improving in-hospital outcomes of pancreatitis alone. In particular, there is considerable room for optimizing the management of new-onset diabetes, exocrine pancreatic insufficiency, and other metabolic sequelae of pancreatitis. The present article provides state-of-the-art information on classification, terminology, and burden of the common sequelae of pancreatitis. A high-risk group of patients with pancreatitis is identified, which is positioned to benefit the most from the metabolic sequelae surveillance program introduced in this article. The program involves continuous follow-up after pancreatitis diagnosis, with the focus on early identification of new-onset diabetes after pancreatitis and exocrine pancreatic insufficiency. The metabolic sequelae surveillance program is scalable and has the potential to reduce the burden of pancreatitis through tertiary prevention in the decades to come.


Standardization of acellular pertussis vaccine by assay of serum neutralizing antibodies to pertussis toxin (antitoxin): analogy with diphtheria toxoid.
Immunity conferred by vaccination with cellular pertussis vaccines and pertussis wanes so that adults are now the main reservoir of B. pertussis. Similar to diphtheria toxoid, acellular pertussis vaccines are suitable for vaccination of adults and it is probable that addition of pertussis toxoid to DT will be recommended for this age group. If this can be achieved, it is easy to predict that pertussis will be eliminated and the possibility of eradicating B. pertussis will become feasible. We propose that, despite the relative inaccuracy of correlating levels of antitoxin with individual immunity, a standardized assay and reference antiserum for pertussis toxoid will control acellular pertussis vaccines as was achieved with diphtheria toxoid.


In vitro labeling of platelets with stable rubidium compounds.
It is a common practice in diagnostic hematology to mark blood cells with radioactive tracers, such as 51Cr, 55Fe, 75Fe, etc., to determine their life-span and study their metabolism. A program has been started to verify the possibility of marking blood cells with stable indicators, assayed by radioisotope-induced X-ray fluorescence analysis. All elements may be considered as indicators aggregating to blood cells, and for in vivo measurements, which are not toxic in the quantities injected, calculated on the basis of the limit of detection of the technique. In this study platelets were marked with a very small quantity of stable compounds of rubidium, a potassium analog. Measurements were carried out in vitro on platelets of normal subjects and in vivo on platelets of rats and rabbits. Several survival curves were deduced and life-span values obtained in accord with previously reported values.


Improved quantitation of delayed-type hypersensitivity responses to sheep erythrocytes in the mouse footpad by estimation of 125I-fibrin deposition.
Footpad swelling in response to subcutaneous antigen challenge is widely used to assess delayed-type hypersensitivity responses to xenogeneic erythrocytes in mice. We report here that quantitation of the deposition of 125I-fibrin, compared with that of 125I-human serum albumin, following intravenous isotope administration, provides a less subjective, convenient and antigen specific index of cell-mediated immunity. Moreover, the results obtained correlate well with in vitro assessment of antigen-specific T cell responses.


Embryonic nervous system genes predominate in searches for dinucleotide simple sequence repeats flanked by conserved sequences.
To study evolution of dinucleotide simple sequence repeats (diSSRs) we searched recently available mammalian genomes for UTR-localized diSSRs with conserved upstream flanking sequences (CFS). There were 252 reported Homo sapiens genes containing the repeats (AC)n, (GT)n, (AG)n or (CT)n in their UTRs including 22 (8.7%) with diSSR-upstream flanking sequences conserved comparing divergent mammalian lineages represented by Homo sapiens and the marsupial, Monodelphis domestica. Of these 22 genes, 19 had known functions including 18 (95%) that proved critical for mammalian nervous systems (Fishers exact test, P<0.0001). The remaining gene, Cd2ap, proved critical for development of kidney podocytes, cells that have multiple similarities to neurons. Gene functions included voltage and chloride channels, synapse-associated proteins, neurotransmitter receptors, axon and dendrite pathfinders, a NeuroD potentiator and other neuronal activities. Repeat length polymorphism was confirmed for 68% of CFS diSSRs even though these repeats were nestled among highly conserved sequences. This finding supports a hypothesis that SSR polymorphism has functional implications. A parallel study was performed on the self-complementary diSSRs (AT)n and (GC)n. When flanked by conserved sequences, the self-complementary diSSR (AT)n was also associated with genes expressed in the developing nervous system. Our findings implicate functional roles for diSSRs in nervous system development.


Identification of the core active structure of a Dendrobium officinale polysaccharide and its protective effect against dextran sulfate sodium-induced colitis via alleviating gut microbiota dysbiosis.
It has been claimed that Dendrobium officinale applied as a functional food in China for centuries derived from the excellent anti-inflammatory activities. Herein, we aim to investigate the core structure of a Dendrobium officinale polysaccharide (DOP) based on the linear structural features by a specific endo-β-1,4-mannanase which was required for the protective effect against dextran sulfate sodium (DSS)-induced colitis in mice. Structure characterization revealed that enzymatic fragment contained the core domain (EDOP) which was composed of glucose and mannose in the molar ratio of 1.00:4.76, and consisted of (1 → 4)-β-D-Glcp and (1 → 4)-β-D-Manp with some attached 2-O-acetylated groups. In colitis mice, both DOP and EDOP could dramatically attenuate the clinical signs via blocking pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and their related mRNA), restoring the levels of short-chain fatty acids (SCFAs), activating the G-protein coupled receptors (GPRs) and modulating the gut microbiota. Gut microbiota dysbiosis is currently considered to be an important factor affecting colitis. The treatment of DOP and EDOP could recall the diversity of gut microbiota and modulate the abundance of the gut microbiota, including increasing the abundance of Bacteroides, Lactobacillus and Ruminococcaceae and reducing the abundance of Proteobacteria. Our findings have suggested that EDOP, as a core domain of DOP, retained similar structural features together with anti-inflammatory activity with DOP, and they could be potentially applied as natural candidates in the treatment of inflammatory bowel disease (IBD).


Surgical overreduction and hyperlordotic fusion of C1-C2 joint are associated with cervical sagittal malalignment.
Previous studies have shown that hyperlordotic C1-C2 fusion was related to postoperative subaxial kyphosis. However, most of the patients in these studies were complicated with rheumatoid arthritis (RA). Moreover, no studies have specifically evaluated the relationship between C1-C2 fusion angle and cervical sagittal vertical axis (cSVA), T1 slope or cranial tilt (CRT) after posterior C1-C2 fusion. This study aimed to investigate the cervical sagittal alignment in non-RA patients following posterior C1-C2 fusion and the correlation between C1-C2 fusion angle and postoperative cervical sagittal alignment. From August 2004 to December 2015, twenty-eight consecutive patients with an average age of 39.2 years (range 6-70 years) who underwent posterior C1-C2 fusion from a single institution were enrolled. The mean follow-up period was 30.7 months (range 12-77 months). Angles of Oc-C1, C1-C2, C2-C3 and C2-C7, cSVA, T1 slope and CRT were measured in lateral cervical radiographs in neutral position before surgery and at the final follow-up. C1-C2 angle significantly increased from 13.6° ± 12.4° to 22.0° ± 8.1° at the final follow-up (P < 0.001). A significant decrease was found both in Oc-C1 and C2-C7 angles from pre-operation to the final follow-up (P < 0.001 and P = 0.011, respectively). Moreover, cSVA and CRT dramatically increased from pre-operation to the final follow-up (P < 0.001). C1-C2 fusion angle was significantly associated with Oc-C1, C2-C7 angle, cSVA and CRT at the final follow-up. A significant correlation was also observed between postoperative change of C1-C2 angle and that of Oc-C1, C2-C7 angle, cSVA and CRT. Apart from decreased subaxial lordosis, posterior C1-C2 fusion in hyperextension may also lead to kyphotic change of atlanto-occipital alignment and increased tilting forward of the cervical spine. Therefore, intraoperative overreduction of C1-C2 angle and hyperlordotic C1-C2 fusion should be avoided to maintain the physiologic cervical sagittal alignment.


Noninvasive approaches to deglutitive aspiration.
Etiologies for aspiration are described. Noninvasive procedures to eliminate aspiration are outlined including postural techniques, variations in bolus volume, viscosity, taste and temperature, methods to enhance oral sensation, swallow maneuvers and exercise programs to improve neuromotor control for swallow. Specific disorders for which each procedure is appropriate are defined.


A Retrospective Analysis of the L3-L4 Disc and Spinopelvic Parameters on Outcomes in Thoracolumbar Fusion: Was Art Steffee Right?
To determine whether the L3-L4 disc angle may be a surrogate marker for global lumbar alignment in thoracolumbar fusion surgery and to explore the relationship between radiographic and patient-reported outcomes after thoracolumbar fusion surgery. Retrospective chart review was conducted on patients who had undergone a lumbar fusion involving levels from T9 to pelvis. EuroQol-Five Dimension (EQ-5D-3L) scores and adverse events including adjacent-segment disease and degeneration, pseudoarthrosis, proximal junctional kyphosis, stenosis, and reoperation were collected. Pre- and postoperative spinopelvic parameters were measured on weight-bearing radiographs, with the L3-L4 disc angle of novel interest. Univariate logistic and linear regression were performed to assess the associations of radiographic parameters with adverse event incidence and improvement in EQ-5D-3L, respectively. In total, 182 patients met inclusion criteria. Univariable analysis revealed that increased magnitude of L3-L4 disc angle, anterior pelvic tilt, and pelvic incidence measures are associated with increased likelihood of developing postoperative adverse events. Conversely, increased lumbar lordosis demonstrated a decreased incidence of developing a postoperative adverse event. Linear regression showed that radiographic parameters did not significantly correlate with postoperative EQ-5D-3L scores, although scores were significantly improved postfusion in all dimensions except Self-Care (P = 0.51). L3-L4 disc angle magnitude may serve as a surrogate marker of global lumbar alignment. The degree of spinopelvic alignment did not correlate to improvement in EQ-5D-3L score in the present study, suggesting that quality of life metric change may not be a sensitive or specific marker of postfusion alignment.