Acquisition of type IX collagen by the developing avian primary corneal stroma and vitreous.
Previous investigations from our laboratory and others have demonstrated that type II collagen, once thought to be a cartilage-specific molecule, is also a component of both the primary corneal stroma and the vitreous of embryonic chickens. In the present immunohistochemical study we have examined the expression in these embryonic matrices of another "cartilage-specific" collagen, type IX, along with type II. In the cornea, type IX collagen is in the primary stroma, but is not detectable in the mature, secondary stroma. Even within the primary stroma this collagen has a brief, transitory existence. It first appears in the peripheral stroma at the time the endothelial cells begin to migrate along its posterior surface, and spreads throughout the stroma during the following 24-36 hr. The epitopes on type IX collagen then suddenly become undetectable just before this matrix swells and becomes populated by the periocular mesenchymal cells (future keratocytes). In comparison, collagen type II (along with type I) is present in the stroma before and long after these events. Deposition of immunodetectable type IX collagen in the developing corneal stroma thus seems to be independent of type II. In the vitreous, we observed type IX collagen along with type II as soon as authentic vitreous could be identified and at all subsequent stages of development. In this tissue, therefore, the expression of collagen types IX and II appears to be coordinate.


Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy.
The concentrations of catecholamines, serotonin, histamine and GABA as well as some of their precursors and metabolites were measured in the CSF and the serum of human patients at different grades of hepatic encephalopathy. In all grades the CSF concentrations of the neurotransmitters were much increased over control levels, while the amount of metabolites varied with the grade of coma. The data suggest modifications of the cerebral turnover of dopamine, norepinephrine and serotonin. The "false transmitters" also occurred in high concentration in all grades of hepatic coma and could play a role in the alterations of synaptic transmission. The present results suggest that the biochemical changes between grade 2 and grade 4 hepatic coma could be due to an inhibition of dopamine beta-hydroxylase. Moreover, the levels of neurotransmitter precursors, tyrosine and 5-hydroxytryptophan, showed enhancement in grades 2 and 3 followed by an important reduction in grade 4. Finally, it seems that the biogenic amines measured in the CSF are of central origin and that their quantification in human lumbar fluid gives new information on the central mechanisms involved in hepatic encephalopathy.


Conformation-based refinement of 18-mer DNA structures.
Nine new crystal structures of CG-rich DNA 18-mers with the sequence 5'-GGTGGGGGC-XZ-GCCCCACC-3', which are related to the bacterial repetitive extragenic palindromes, are reported. 18-mer oligonucleotides with the central XZ dinucleotide systematically mutated to all 16 sequences show complex behavior in solution, but all ten so far successfully crystallized 18-mers crystallized as A-form duplexes. The refinement protocol benefited from the recurrent use of geometries of the dinucleotide conformer (NtC) classes as refinement restraints in regions of poor electron density. The restraints are automatically generated at the dnatco.datmos.org web service and are available for download. This NtC-driven protocol significantly helped to stabilize the structure refinement. The NtC-driven refinement protocol can be adapted to other low-resolution data such as cryo-EM maps. To test the quality of the final structural models, a novel validation method based on comparison of the electron density and conformational similarity to the NtC classes was employed.


Effects of motion related outliers in dynamic functional connectivity using the sliding window method.
It has been suggested that the use of window functions, other than the rectangular, in the sliding window method, may be beneficial for reducing the effects of motion-related outliers in the time-series, when assessing dynamic functional connectivity (dFC) in resting-state fMRI (rs-fMRI). Ten window functions for a wide range of window lengths (20-150 s) combined with Pearson and Kendall correlation metrics, were investigated. One hundred high quality rs-fMRI datasets from healthy controls, were used to systematically assess the effect of varying the window function and length on dFC assessment. To this end, two approaches were implemented: a) simulated outliers were added to the experimental data and b) the experimental data were divided into low and high motion subgroups. The presence of experimental motion-noise tended to inflate the number of dynamic connections for longer (≥100 s) wide-shaped windows, while shorter (20-30 s) narrow-shaped windows exhibited increased sensitivity in the presence of simulated outliers. Moreover, window sizes from 60 s to 90 s were mildly affected by motion-related effects. In most cases, the number of dynamic connections increased, and gradually lower frequencies were captured, with an increasing window size. Subject motion considerably affects the obtained dFC patterns; thus, it is preferable to perform motion artefact removal in the pre-processing stage rather than using alternative window functions to mitigate their effects. Provided that motion-noise is not excessive, the choice of a rectangular window is adequate. Finally, low frequency oscillations in functional connectivity seem to play an important role in the context of dFC assessment.


Roux-en-Y choledochojejunostomy versus duct-to-duct biliary anastomosis in liver transplantation for primary sclerosing cholangitis: a meta-analysis.
Roux-en-Y choledochojejunostomy and duct-to-duct anastomosis are potential methods for biliary reconstruction in liver transplantation (LT) for recipients with primary sclerosing cholangitis (PSC). However, there is controversy over which method yields superior outcomes. The purpose of this study was to evaluate the outcomes of duct-to-duct versus Roux-en-Y biliary anastomosis in patients undergoing LT for PSC. Studies comparing Roux-en-Y versus duct-to-duct anastomosis during LT for PSC were identified based on systematic searches of 9 electronic databases and multiple sources of gray literature. The search identified 496 citations, including 7 retrospective series, and 692 patients met eligibility criteria. The use of duct-to-duct anastomosis was not associated with a significant difference in clinical outcomes, including 1-year recipient survival rates (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.65-1.60; P = .95), 1-year graft survival rates (OR, 1.11; 95% CI, 0.72-1.71; P = .64), risk of biliary leaks (OR, 1.23; 95% CI, 0.59-2.59; P = .33), risk of biliary strictures (OR, 1.99; 95% CI, 0.98-4.06; P = .06), or rate of recurrence of PSC (OR, 0.94; 95% CI, 0.19-4.78; P = .94). There were no significant differences in 1-year recipient survival, 1-year graft survival, risk of biliary complications, and PSC recurrence between Roux-en-Y and duct-to-duct biliary anastomosis in LT for PSC.


Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study.
Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01). Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.


Results of R0 resection for colorectal liver metastases associated with extrahepatic disease.
Extrahepatic malignant disease has always been considered an absolute contraindication to hepatectomy for colorectal liver metastases. This study reports the long-term outcome and prognostic factors of patients undergoing extrahepatic disease resection simultaneously with hepatectomy for liver metastases. From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal liver metastases. They were inscribed in a registry and then prospectively followed up. They represented 25% of the 294 patients who underwent an R0 hepatectomy for colorectal liver metastases during the same period. The mortality rate was 2.7%, and morbidity was 25%. After a median follow-up of 4.9 years (range, 1.7-13.4 years), the overall 3- and 5-year survival rates were 45% and 28%, respectively. By using a Cox model, there was a significant difference in survival between patients with single versus multiple sites of extrahepatic disease. Also, the presence of more than five liver metastases was a significant parameter. Extrahepatic disease in colorectal cancer patients with liver metastases should no longer be considered as a contraindication to hepatectomy. However, this intended R0 resection cannot be performed in 50% of laparotomized patients, and negative prognostic factors for surgery include the presence of multiple extrahepatic disease sites or more than five liver metastases.


Distribution of dopamine immunoreactivity in the brain of the mormyrid teleost Gnathonemus petersii.
The distribution of dopamine-containing cell bodies and fibers was studied with aid of specific antibodies against dopamine in the highly developed brain of the weakly electric fish Gnathonemus petersii. In the telencephalon, dopamine-containing cell bodies were observed in a small area, i.e., area ventralis pars dorsalis and supracommissuralis. In the diencephalon, moderate numbers of dispersed dopamine-immunoreactive cells were present in the preoptic region, while large numbers of dopamine-containing neurons occurred in the hypothalamic paraventricular organ and neighbouring regions. The paraventricular organ, located around small (anterior, intermediate, and posterior) recesses contained many dopamine-immunoreactive cerebrospinal fluid-(CSF)-contacting neurons. Dopamine-containing cells were also observed in a magnocellular hypothalamic cell group, in the nucleus of the lateral recess, and in the nucleus posterior tuberis. In the mesencephalon only a few dopamine-containing cells were observed in a dorsal tegmental (possibly pretectal) area, whereas in ventral mesencephalic regions dopamine-containing cells were lacking. More caudally, dopamine-containing cells were observed in the presumed locus coeruleus, in the caudal region of the reticular formation, and in the presumed area postrema. Dopamine-immunoreactive fiber density was very high in the medioventral hypothalamus and in the preoptic region, where a dense subependymal plexus was observed along the preoptic recess. Such a plexus was also present in the caudal rhombencephalon, where it probably arises from the area postrema. Moderate numbers of dopamine-immunoreactive fibers were present in medioventral parts of the brain along its total rostrocaudal extent as well as in several subnuclei of the torus semicircularis, in the tectum mesencephali, and in the medial part of the dorsal telencephalic area. Other parts of the dorsal telencephalic area, as well as the large cerebellum and the electrosensory lateral line lobe of Gnathonemus, did not contain detectable amounts of dopamine. In spite of the high differentiation of the brain of Gnathonemus, the distribution of catecholamines as visualized with dopamine immunohistochemistry appears to be basically similar to that described in other teleostean and actinopterygian fishes on the basis of formaldehyde-induced fluorescence or tyrosine hydroxylase immunohistochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)


Dynamic training of the lumbar musculature to prevent recurrence of acute low back pain: a randomized controlled trial using a daily pain recall for 1 year.
The purpose of this experiment was to quantify lumbar muscle endurance training for individuals with a recent episode of acute low back pain (LBP) (≥ moderate pain for ≥ 2 days) and to observe whether the training would reduce the rate and severity of recurrent LBP episodes. Twenty-six participants who were pain-free at the time of the study were randomly divided into a high intensity back endurance (HIBE)-trained or a low intensity abdominal (LOAB)-trained (control) group. The HIBE-trained group performed preloaded maximum isokinetic exertions of the back extensors (five sets of 10 repetitions, 3 days a week for 4 weeks, totaling 12 sessions). The LOAB-trained group performed low intensity isometric contractions on their abdominals that had minimal effect on their back musculature. The two groups reported daily pain logs on a weekly basis on an interactive voice response telephone system for 1 year. The HIBE-trained group experienced more pain days (p = 0.038) in the minor and moderate categories and more episodes of acute LBP than the LOAB-trained group. However, there was a trend of less pain in the severe, intense and excruciating categories in the HIBE-trained group. The results of this experiment did not provide evidence that short-term intense training of the low back musculature provides protection against future episodes of LBP.


New aspects of the relationship among hypertension, obesity, and the kidneys.
Recent studies have highlighted the association between obesity and chronic renal disease. Overweight has been shown to be a survival advantage in patients on maintenance hemodialysis therapy. However, in patients with preterminal renal failure, obesity may contribute to the progression of renal disease. Data collected from the Prevention of Renal and Vascular End-stage Disease study suggest that changes in weight directly influence albuminuria, hinting that albumin excretion could be used in the general population as a surrogate marker for risk of developing chronic kidney disease. The causal pathways linking excess weight to chronic kidney disease and hypertension are briefly reviewed in this article, and therapeutic approaches to combat this growing health problem are highlighted.


Comparison of three ultrasound methods of measuring the diameter of the abdominal aorta.
Three ultrasound methods of measuring the diameter of the abdominal aorta exist: the outer-to-outer (OTO) method, where callipers are placed on the outer layer of the aortic wall; the inner-to-inner (ITI) method, where callipers are placed on the inner layer of the aortic wall; and the leading edge-to-leading edge (LELE) method, where callipers are placed on the outer layer of the anterior wall and the inner layer of the posterior wall. The aim was to determine the variability of the three methods, differences between them, and the consequences on prevalence estimates. Some 127 consecutive patients with a small abdominal aortic aneurysm (AAA) were included. The maximal anteroposterior diameter was measured using the OTO, ITI and LELE methods by two vascular sonographers who were blinded to each other's measurements. The variability was described as the standard deviation. The variability was 2.7 (95 per cent limits of agreements ± 5.4) mm for the OTO, 2.3 (± 4.6) mm for the ITI and 2.0 (± 4.0) mm for the LELE method. The corresponding coefficients of variability were 6.4, 6.1 and 5.0 per cent. The difference was 4.1 mm between ITI and OTO (P < 0.001), 2.0 mm between ITI and LELE (P < 0.001), and 2.1 mm between LELE and OTO (P < 0.001). LELE measurement was the most reproducible method of measuring the abdominal aorta. All methods showed a high degree of variability.


Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment.
The ICH S7B guidelines recommend that all new chemical entities should be subjected to hERG repolarization screening due to its association with life-threatening "Torsades de Pointes" (TdP) arrhythmia. However, it has become evident that not all hERG channel inhibitors result in TdP and not all compounds that induce QT prolongation and TdP necessarily inhibit hERG. In order to address the limitations of the S7B/E14 guidelines, the FDA through a public/private partnership initiated the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative to examine the possible modification and refinement of the ICH E14/S7B guidelines. One of the main components of the CiPA initiative is to utilize a predictive assay system together with human cardiomyocytes for risk assessment of arrhythmia. In this manuscript we utilize the xCELLigence® CardioECR system which simultaneously measures excitation-contraction coupling together with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to assess the effect of 8 reference compounds across 3 different independent sites. These 8 compounds were part of Phase I CiPA validation study. Our data demonstrate that hERG channel blockers, such as E4031 and moxifloxacin, prolonged field potential duration (FPD) at low concentration and induced arrhythmic beating activity as measured by field potential (FP) recording and impedance (IMP) recordings at higher concentrations. On the contrary, nifedipine, an inhibitor of calcium channel, didn't disrupt the periodicity of cell beating and weakened cell contractile activity and shortened FPD. Multichannel inhibitors, such as flecainide, quinidine and mexiletine, not only increased FPD and induced arrhythmia but also significantly reduced the amplitude of FP spike. JNJ303, an IKs inhibitor, only affected FPD. Comparison of the compound effect on FPD across the 3 different sites is consistent in terms of trend of the effect with observed 3-10 fold differences in minimal effective concentration at which a minimum of 10% response is detected. In addition, pentamidine, a hERG trafficking inhibitor which induced irregular beating activity over a more prolonged duration of time was readily flagged in this assay system. Taken together, this multi-parameter assay using hiPSC-CMs in conjunction with simultaneous measurement of ion channel activity and contractility can be a reliable approach for risk assessment of proarrhythmic compounds.


Determinants of response to the glucagon-like peptide-1 receptor agonists in a type 2 diabetes population in the real-world.
To identify clinical predictors associated with a response in terms of glycemic control and weight loss in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). A retrospective observational study was performed with real-world databases in primary care. Patients with type 2 diabetes-initiated treatment with GLP-1RAs during the study period, and response to GLP-1RAs were determined six months from treatment initiation. An optimal glycated hemoglobin (HbA1c) or weight response was defined as a reduction of ≥ 1% or ≥ 3%, respectively. A "great" response was defined as both an optimal HbA1c and weight response. Bivariate and multivariate analyses with intention-to-treat were performed. A sample of 2944 patients with type 2 diabetes was recruited. Higher HbA1c at baseline was the main clinical predictor of an optimal HbA1c response (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 1.96-2.71 in men and OR: 2.03, 95% CI: 1.76-2.33 in women). Treatment without insulin at baseline was associated with a greater weight reduction in men (OR: 2.50, 95% CI: 1.41-4.44). Older age and a higher weight at baseline were related with this in women (OR: 1.02, 95% CI: 1.00-1.05 and OR: 1.01, 95% CI: 1.00-1.02, respectively). A high HbA1c at baseline and previous non-insulin therapy were the main predictors of a greater response (optimal HbA1c and weight response) to GLP1ra in both men and women. This may aid in treatment decision-making before initiating treatment with GLP-1RAs.


Publications by family medicine faculty in the biomedical literature: 1989-1999.
Concern has been expressed about a possible decrease in publication productivity of family medicine faculty. This study measured trends in publication productivity by family medicine faculty from 1989 to 1999 and determined the journals in which these individuals published their work. A sample of Society of Teachers of Family Medicine (STFM) members was identified from the STFM membership roster The sample included 900 members from 1980, 1,801 members from 1994, and 1,524 members from 1999. A MEDLINE search was performed to determine how many articles each individual published during those years and in what journals the articles were published. An estimate was made of the total publication productivity of all STFM members. The percentage of STFM members publishing at least one article in 1989, 1994, and 1999 was 16%, 16.3%, and 8.5%, respectively. The estimated total number of publications by all STFM members in all journals was 729 in 1989,1,040 in 1994, and 669 in 1999. The journals in which STFM members most frequently published were the Journal of Family Practice, Family Medicine, and Academic Medicine; 32% of all publications appeared in those three journals. The number of publications in high-profile interdisciplinary journals was very small. Based on a MEDLINE search of a large sample of STFM members' publication records, it appears that the publication productivity of the STFM membership is decreasing.


Factor XII-dependent fibrinolysis: a double function of plasma kallikrein and the occurrence of a previously undescribed factor XII- and kallikrein-dependent plasminogen proactivator.
Fibrinolytic studies in euglobulin fractions of Fletcher trait plasma (deficient in prekallikrein) revealed reduced activities as compared to normal plasma. A quantitative assay for total plasminogen activator plus proactivator in plasma showed that the amount in Fletcher trait patients is about half of normal (normal = +/- 100 blood activator units [BAU]/ml). Plasma kallikrein partially purified in a high and low molecular weight form exerted plasminogen activator activity amounting to 10-15 BAU/ml plasma. So, the absence of kallikrein in the deficient plasma cannot fully account for the reduction in activator activity. Additions of kallikrein preparations or normal plasma fractions resulted in additional activator activity in Fletcher trait plasma which was assessed at 30-40 BAU/ml. This activity was assumed to originate from a previously undescribed plasminogen proactivator whose activation is kallikrein- and factor XII-dependent. Fractionation experiments demonstrated the presence of two major activities and a minor activity caused by kallikrein in normal plasma. It is concluded that plasma kallikrein has two functions in the generation of factor XII-dependent fibrinolytic activity: one as a direct plasminogen activator and another as a factor in the activation of a major factor XII-dependent plasminogen proactivator.


Regulation of mammalian target of rapamycin complex 1 by Bcl-2 and Bcl-XL proteins.
Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and metabolism. Its activity is controlled by various types of signals, including growth factors, nutrients, and stresses. In this study, we show that changes in expression levels of two antiapoptotic proteins, Bcl-2 and Bcl-XL, also affect mTORC1 signaling activity. In cells overexpressing Bcl-XL, mTORC1 activity is increased and becomes less sensitive to growth factor or nutrient conditions. In contrast, reduction in expression levels of the two antiapoptotic proteins inhibits mTORC1 signaling activity. Our results suggest that the effect of Bcl-2 and Bcl-XL on mTORC1 is mediated by FKBP38, an inhibitor of mTORC1. The two proteins compete with mTORC1 for FKBP38 binding and hence alter mTORC1 activity. This study reveals a novel cross-talk between Bcl-2/XL and mTORC1 signaling, which is likely to contribute to cancer development.


Association between osteosarcopenia and coronary artery calcification in asymptomatic individuals.
Osteoporosis and sarcopenia are substantially interrelated with shared cardiovascular risk factors. However, the relationship between osteosarcopenia and coronary artery disease is largely unexplored. We aimed to investigate the association between osteosarcopenia and coronary artery calcification (CAC) scores in asymptomatic adults. A total of 5969 asymptomatic adults without cardiovascular disease who underwent a health examination including estimation of CAC scores by cardiac tomography were analyzed. Osteoporosis was defined as low bone mineral density T-score ≤ - 2.5 standard deviation, and sarcopenia as appendicular skeletal muscle mass < 5.7 kg/m2 for women and < 7.0 kg/m2 for men, and osteosarcopenia as the copresence of both osteoporosis and sarcopenia. Participants were divided into four groups according to the presence of osteoporosis and/or sarcopenia as control, sarcopenia alone, osteoporosis alone, and osteosarcopenia. Prevalence of CAC was 22.0% in control, 23.6% in sarcopenia alone, 38.5% in osteoporosis alone, and 48.3% in osteosarcopenia group, with the osteosarcopenia group showing the highest (p < 0.0001). After adjustments for possible confounders, mean of log (CAC score + 1) in osteosarcopenia group was higher than other three groups (Bonferroni p < 0.0001). Using multivariate-adjusted analysis, subjects with osteosarcopenia had the highest risk for having CAC > 0 (odds ratio [OR] 2.868; 95% confidence interval [CI] 1.717-4.790). Furthermore, subjects with osteosarcopenia had a significant risk of moderate-to-extensive CAC (CAC score ≥ 100) (OR 2.709; 95% CI 1.128-6.505). We demonstrated that osteosarcopenia was independently associated with a higher prevalence of subclinical coronary atherosclerosis. Our results suggest osteosarcopenia as a predisposing factor for coronary heart disease.


Reduction of Venous Thromboembolism in Surgical Patients Using a Mandatory Risk-Scoring System: 5-Year Follow-Up of an American College of Surgeons National Surgical Quality Improvement Program.
Sheikh Khalifa Medical City's (SKMC) surgery institute was identified as a high outlier in the incidence of venous thromboembolism (VTE; deep vein thrombosis [DVT] and pulmonary embolism [PE]) based on the semiannual report of the American College of Surgeon's National Surgical Quality Improvement Program (ACS NSQIP) in June 2010. To report our rates of VTE at SKMC, the results, and 5-year follow-up after an ACS NSQIP quality improvement program. A multidisciplinary VTE task force was established in June 2010. We instituted a compulsory risk assessment for VTE and utilized the ACS NSQIP best practice guidelines to review cases of VTE. We prospectively evaluated the observed/expected (O/E) ratio for DVT/PE after implementing the action plan. The O/E ratio for PE/DVT in general and general/vascular (GV) surgery was 6.00 and 4.86 in June 2010. Our compliance with ordering antithrombotic prophylactic measures was as low and it improved to 100% and our O/E ratio decreased to 1.18 and 1.5 in July 2011 and stabilized for the next 4 years. Currently, our compliance with ordering antithrombotic prophylactic measures is 100%, and our last 2 O/E ratio for DVT/PE are 0.74 and 0.75 in GV surgery and 0.82 and 0.78 in the entire surgery institute, respectively, and we are considered an exemplary site of the ACS NSQIP in GV surgery. A compulsory risk assessment for VTE has led to an overall improvement in DVT/PE rates in the surgery institute and for GV surgery to become an exemplary site for the ACS NSQIP.


The vehicle tray revisited: the use of the vehicle tray in assessing allergic contact dermatitis by a 24-hour application method.
Over 700 patients were screened by patch testing for sensitivity to the components of a vehicle tray from July 1974 through June 1976 at the Mayo Clinic. A modified version of the vehicle tray originally suggested by Fisher et al. (1971) was used, containing 14 substances commonly found in vehicles. Patches were applied for 24 rather than the usual 48 hours. Our percentage of reactivity compares favorably with the 48-h application method, thus demonstrating the efficacy of this time-saving technique. The method and usefulness of determining a percentage of irritancy are discussed. This was found to be a valuable tool in assessing false-positive reactions among our percentage of reactivity. Four irritants were demonstrated: phenylmercuric acetate (0.05% pet.), sodium lauryl sulfate (1% aq), thimerosal (0.1% aq) and hexachlorophene (1% pet.).


Pseudosarcomatous myofibroblastic proliferations of the urinary bladder are neoplasms characterized by recurrent FN1-ALK fusions.
Pseudosarcomatous myofibroblastic proliferation is a descriptive term that designates a group of clinically indolent genitourinary lesions that most commonly arise in the urinary bladder. Given that pseudosarcomatous myofibroblastic proliferation may show morphologic overlap with inflammatory myofibroblastic tumor, the relationship, if any, between the two entities has been unclear. Moreover, pseudosarcomatous myofibroblastic proliferations are known to be positive for ALK immunohistochemistry in a subset of cases, although an inconsistent association with ALK rearrangement (ranging from 0 to 60%) has been reported. The objectives of this study were to determine the frequency of ALK rearrangement and to identify fusion partners using fluorescence in situ hybridization (FISH) and targeted RNA sequencing studies in a contemporary series of 30 pseudosarcomatous myofibroblastic proliferations of the urinary bladder, as well as to investigate ROS1 status by immunohistochemistry. ALK immunohistochemistry was positive in 70% (21/30) of pseudosarcomatous myofibroblastic proliferations; ROS1 immunohistochemistry was consistently negative (0/28). ALK rearrangements were detected by FISH in 86% (18/21) of cases, correlating with ALK immunohistochemical positivity in all but 3 cases. Of eight cases confirmed to be ALK rearranged by FISH, targeted RNA-sequencing detected FN1-ALK fusions in seven (88%) cases, which involved exons 20-26 of FN1 (5') and exon 18-19 of ALK (3'). In conclusion, ALK rearrangements are frequent in pseudosarcomatous myofibroblastic proliferations, typically involving exon 19, and FN1 appears to be a consistent fusion partner. Given the significant clinicopathologic differences between inflammatory myofibroblastic tumor and pseudosarcomatous myofibroblastic proliferation, our findings provide further support for classification of pseudosarcomatous myofibroblastic proliferation as a distinct clinicopathologic entity, and propose the alternate terminology "pseudosarcomatous myofibroblastic neoplasm of the genitourinary tract."


Crash involvement during the different phases of the New Zealand Graduated Driver Licensing System (GDLS).
The New Zealand Graduated Driver Licensing System (GDLS) is designed to allow novice drivers to gain driving experience under conditions of reduced risk. To examine the effectiveness of the GDLS, an analysis of how the crash involvement of novice drivers changes as drivers move through the GDLS was undertaken. Crash profiles were created by data matching the New Zealand license and crash databases, covering a time period from 1999-2006. The crash profiles show that the initial learner period of the GDLS is relatively safe and the time at which novice drivers have the highest rate of crash involvement is during the first few months of solo driving. Analysis using logistic regression also showed an effect of age and gender, with higher crash involvement associated with younger drivers and males. In addition, individuals who gained a full license within 12-18 months of holding a restricted license, due to completion of a time-discount associated educational program, had a higher level of involvement in crashes than individuals who gained a full license after 18 months. The crash profiles provide an insight into the crash risk associated with different phases of the New Zealand GDLS. Increasing the age at which drivers first begin to solo drive and the removal of the time-discount associated with completion of an educational program should be considered.


Circling back to PTEN: Fumarate inhibits canonical tumor suppressor.
Ge et al. (2022) describes an inhibitory, post-translational modification of PTEN at C211 by fumarate, which offers new insight into the integration of PI3K signaling and metabolism via a potential feedforward regulatory mechanism involving a PI3K-glucose-fumarate-PTEN axis.


Diagnostic significance of parafibromin expression in parathyroid carcinoma.
Parathyroid carcinomas are difficult to distinguish from adenomas according to the current diagnostic criteria. The judgment of local infiltration is subjective and inconsistent. Existing studies have found that the CDC73 gene encoding parafibromin is related to the occurrence of parathyroid carcinomas. This study is aimed at investigating whether the immunohistochemistry of parafibromin is helpful in distinguishing malignant from benign parathyroid tumors. A total of 53 patients with parathyroid carcinoma from Peking Union Medical College Hospital were included. Metastasis was found in 17 of 53 patients. In addition, another 53 patients with parathyroid adenomas were included as controls. Appropriate sections were stained with an immunohistochemical autostainer. Three senior pathologists evaluated the sections and analyzed their clinicopathological features independently. The loss of parafibromin expression only occurred in malignant tumors, including all carcinomas with metastasis (17/17) and 14 of 36 carcinomas with only local infiltration. All staining results of adenomas (53/53) were positive. Considering invasion as the gold standard of malignancy, the sensitivity of parafibromin staining is 58%, and the specificity is 100%. If the gold standard is changed to metastasis, the sensitivity becomes 100%, and the specificity becomes 84%. By analyzing clinicopathological features with metastasis and parafibromin staining, it is found that local-infiltrative carcinomas with positive staining results have better biological behaviors than carcinomas that lack parafibromin expression. Parafibromin staining is highly recommended as an auxiliary method in the diagnosis of parathyroid carcinoma.


Capsaicin-induced neuronal death and proliferation of the primary sensory neurons located in the nodose ganglia of adult rats.
To evaluate the potential for neuronal replacement following destruction of vagal afferent neurons, we examined nodose ganglia following i.p. capsaicin treatment of adult rats. Rats received capsaicin or vehicle followed by a regimen of 5'-bromo-2'-deoxyuridine injections (BrdU) to reveal DNA replication. Nodose ganglia were harvested at various times post-treatment and processed for 4',6-diamidino-2-phenylindole (DAPI) nuclear staining and immunofluorescence to estimate neuronal numbers and to determine vanilloid receptor, cleaved caspase 3, TUNEL, BrdU, the neuron-selective marker protein gene product (PGP) -9.5 and neurofilament-M-immunoreactivity. Twenty-four hours after capsaicin approximately 40% of nodose ganglion neurons expressed cleaved caspase 3-immunoreactivity and 16% revealed TUNEL staining, indicating that primary sensory neurons are killed by the capsaicin treatment of adult rats. The occurrence of neuronal death was confirmed by counts of DAPI-stained neuronal nuclei, which revealed >or=50% reduction of nodose neuron number by 30 days post-capsaicin. However, by 60 days post-capsaicin, the total numbers of neuronal nuclei in nodose ganglia from capsaicin-treated rats were not different from controls, suggesting that new neurons had been added to the nodose ganglia. Neuronal proliferation was confirmed by significant BrdU incorporation in nuclei of nodose ganglion cells immunoreactive for the neuron-specific antigen PGP-9.5 revealed 30 and 60 days post-capsaicin. Collectively, these observations suggest that in adult rats massive scale neurogenesis occurs in nodose ganglia following capsaicin-induced neuronal destruction. The adult nodose ganglion, therefore, provides a novel system for studying neural plasticity and adult neurogenesis after peripheral injury of primary sensory neurons.


INTEGRATING CHRONIC KIDNEY DISEASE PATIENT'S SPIRITUALITY IN THEIR CARE: HEALTH BENEFITS AND RESEARCH PERSPECTIVES.
Patients who suffer from chronic renal disease face problems in many aspects of their life; problems such as physical and social as well as mental such as stress, anxiety, depression. In addition, they exhibit an amount of spiritual needs, which relate and influence the psychological adaptation to the illness. The aim of this article is to examine evidence from the international literature regarding the possible relation of spirituality and health outcomes, mostly in the complex codex of a chronic and life treathing disease such as CKD. Spirituality is a very debatable issue and the term has no single and widely agreed definition. The key components of spirituality were 'meaning', 'hope', 'relatedness/connectedness', and 'beliefs/beliefs systems'. Spirituality has been characterized as the quest for meaning in life, mainly through experiences and expressions of mind, in a unique and dynamic process different for each individual. For many individuals spirituality and religion are important aspects of their existence, constituting a source support contribute to wellbeing and coping with life's daily difficulties. Considering, assessing and addressing chronic kidney disease patient's spirituality and spiritual needs is necessary and it can have a positive outcome in health related quality of life, mental health and life expectancy.


Micellization and solubilization of phospholipids by surfactants.
Phospholipids comprise the major component that defines biological membranes. Yet these amphiphilic molecules exist as liquid crystals when they are dispersed in water. Surfactants which form micelles in aqueous solution are quite useful in solubilizing the phospholipids by converting them into mixed micelles. Phospholipids containing short-chain fatty acids have also been chemically synthesized and these form micelles themselves without added surfactants. Below their cmc, monomers of these synthetic phospholipids can be co-micellized with surfactants. The solubilization of natural phospholipids and the micellization of synthetic phospholipids as well as their co-micellization by surfactants will be discussed. Emphasis will be placed on nonionic surfactants where the formation of micelles and mixed micelles with phospholipids has been well studied.


Operative treatment of intraarticular calcaneal fractures: Anatomical and functional outcome of three different operative techniques.
Management of the intraarticular calcaneal fracture is a challenge. The optimal method of treatment remains controversial. This study evaluates the anatomical and functional postoperative outcomes of displaced intraarticular calcaneal fractures that have been treated using three different techniques of ORIF. Between 2004 and 2011 we treated 143 patients with calcaneal fractures, 40 of these patients (28%) were treated conservatively. This is a retrospective study of the remaining 103 patients (72%) who were operated on consecutively, mainly by one surgeon (NG). Calcaneal fractures were classified according to the Sanders classification. Three types of osteosynthesis were used: standard anatomical plate (SP), locking anatomical plate (LCP) and standard anatomical plate with autologous bone graft (SP+ABG). Clinical outcome was assessed one year after the operation: anatomical reduction was evaluated according to the analysis of Bohler's angle at final follow-up, and functional assessment was conducted using the Maryland Foot Score (MFS). The fractures were classified as follows: 35 (34%) Sanders type II, 47 (45.6%) Sanders type III and 21 (20.4%) Sanders type IV. The SP was used in 67 (65%) fractures, LCP in 16 (15.5%) and SP+ABH in 20 (19.4%). The correlation test showed a weak association between the Sanders fracture type and the operation technique (Pearson correlation coefficient r=0.26). The non-parametric tests showed that the fracture type did not significantly influence the postoperative Bohler's angle outcome (p=0.132), or the type of operation (p=0.664). Excellent or good reduction of the posterior calcaneal facet was achieved in all operated fractures. One year after the operation, the distribution of Bohler's angle was normal with a mean 31.9° (SD 4.84) in all three groups. There was no significant difference in the functional postoperative outcome in terms of MFS in the three groups (p=0.601), but the Sanders fracture type had significant influence on the functional postoperative outcome in terms of MFS (p=0.001). In the representative sample of 103 operatively treated intraarticular calcaneal fractures, anatomical and functional postoperative efficacy outcomes appeared to be similar in all three treatment groups. High-grade displaced intraarticular calcaneal fractures (Sanders IV) had worse functional results irrespective of the type of operation. The optimal method for management of intraarticular calcaneal fracture is operative, using the standard anatomic calcaneal plate. Autologous bone grafting is not required. Large sample comparative studies are still needed.


Activation of mitochondrial calcium-independent phospholipase A2γ (iPLA2γ) by divalent cations mediating arachidonate release and production of downstream eicosanoids.
Calcium-independent phospholipase A(2)γ (iPLA(2)γ) (PNPLA8) is the predominant phospholipase activity in mammalian mitochondria. However, the chemical mechanisms that regulate its activity are unknown. Here, we utilize iPLA(2)γ gain of function and loss of function genetic models to demonstrate the robust activation of iPLA(2)γ in murine myocardial mitochondria by Ca(2+) or Mg(2+) ions. Calcium ion stimulated the production of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) from 1-palmitoyl-2-[(14)C]arachidonoyl-sn-glycero-3-phosphocholine during incubations with wild-type heart mitochondrial homogenates. Furthermore, incubation of mitochondrial homogenates from transgenic myocardium expressing iPLA(2)γ resulted in 13- and 25-fold increases in the initial rate of radiolabeled 2-AA-LPC and arachidonic acid (AA) production, respectively, in the presence of calcium ion. Mass spectrometric analysis of the products of calcium-activated hydrolysis of endogenous mitochondrial phospholipids in transgenic iPLA(2)γ mitochondria revealed the robust production of AA, 2-AA-LPC, and 2-docosahexaenoyl-LPC that was over 10-fold greater than wild-type mitochondria. The mechanism-based inhibitor (R)-(E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL) (iPLA(2)γ selective), but not its enantiomer, (S)-BEL (iPLA(2)β selective) or pyrrolidine (cytosolic PLA(2)α selective), markedly attenuated Ca(2+)-dependent fatty acid release and polyunsaturated LPC production. Moreover, Ca(2+)-induced iPLA(2)γ activation was accompanied by the production of downstream eicosanoid metabolites that were nearly completely ablated by (R)-BEL or by genetic ablation of iPLA(2)γ. Intriguingly, Ca(2+)-induced iPLA(2)γ activation was completely inhibited by long-chain acyl-CoA (IC(50) ∼20 μm) as well as by a nonhydrolyzable acyl-CoA thioether analog. Collectively, these results demonstrate that mitochondrial iPLA(2)γ is activated by divalent cations and inhibited by acyl-CoA modulating the generation of biologically active metabolites that regulate mitochondrial bioenergetic and signaling functions.


Safety Summary of Pediatric Inflammatory Bowel Disease Therapies.
Therapeutic options for the treatment of pediatric inflammatory bowel disease include aminosalicylates, enteral nutrition, corticosteroids, immunomodulators, biologics, and emerging small molecule agents. Infectious risk due to systemic immunosuppression should be mitigated by appropriate screening before therapy initiation. Rare but serious malignancies have been associated with thiopurine use alone and in combination with anti-tumor necrosis factor agents, often in the setting of a primary Epstein-Barr virus infection. Potential agent-specific adverse events such as cytopenias, hepatotoxicity, and nephrotoxicity warrant regular clinical and laboratory monitoring.


Scleral exposure changes after Le Fort I maxillary advancement with vertical component in individuals with skeletal Class III malocclusion-A stereophotogrammetric image study.
This retrospective study aimed to evaluate inferior scleral exposure changes in Class III patients that underwent orthognathic surgery with Le Fort I osteotomy with and without vertical displacement. Preoperative and 6 months postoperative cephalograms and stereophotogrammetric images of 45 subjects (mean age: 21.66 ± 2.97 years) who underwent orthognathic surgery for Class III correction were retrieved. Subjects were divided into 3 groups: maxillary advancement-only (AO), maxillary advancement + impaction (AI) and maxillary advancement + downfracture (AD). Exclusion criteria were mandibular-only surgery, occlusal canting, facial asymmetry, orbital surgery and craniofacial syndrome. One investigator measured inferior scleral exposure on both sides using following landmarks: upper eyelid margin (A), inferior limbus (B) and lower eyelid margin (C). Distance between A and C was recorded as overall eye height (E), and distance between B and C was recorded as inferior sclera exposure (S). S:E ratio in percentage was calculated to standardize sclera exposure relative to overall eye height. Wilcoxon signed-rank and Kruskal-Wallis tests were used for statistical analysis (P < .05). Mean value of maxillary movements was as follows: 4.21 ± 1.82 mm advancement in AO, 5.08 ± 2.18 mm advancement and 2.33 ± 0.99 mm impaction in AI, 3.95 ± 1.45 mm advancement and 3.1 ± 0.71 mm downfracture in AD. Change in reduction of scleral exposure was significant in all groups (P < .05). AI group bilaterally and AO group right side had highest differences (-4.96 ± 4.86, -6.09 ± 4.21, -4.99 ± 3.23, respectively). There was no significant difference between groups in S:E ratio changes (P > .05). Intergroup comparisons showed no statistically significant difference, revealing similar reduction in all three groups despite the differences in the vertical movement variable.


Mobile ER-to-Golgi but not post-Golgi membrane transport carriers disappear during the terminal myogenic differentiation.
The organelles of the exocytic pathway undergo a profound reorganization during the myogenic differentiation. Here, we have investigated the dynamics of the membrane trafficking at various stages of the differentiation process by using the green fluorescent protein-tagged, temperature-sensitive vesicular stomatitis virus G protein (tsG-GFP) as a marker. At the restrictive temperature of 39°C, the tsG-GFP located to the endoplasmic reticulum (ER) at each stage of differentiation. Mobile membrane containers moving from the ER to the Golgi elements were seen in myoblasts and myotubes upon shifting the temperature to 20°C. In adult myofibers, in contrast, such containers were not seen although the tsG-GFP rapidly shifted from the ER to the Golgi elements. The mobility of tsG-GFP in the myofiber ER was restricted, suggesting localization in an ER sub-compartment. Contrasting with the ER-to-Golgi trafficking, transport from the Golgi elements to the plasma membrane involved mobile transport containers in all differentiation stages. These findings indicate that ER-to-Golgi trafficking in adult skeletal myofibers does not involve long-distance moving membrane carriers as occurs in other mammalian cell types.


Differential stripping demonstrates a significant reduction of the hair follicle reservoir in vitro compared to in vivo.
Penetration studies are commonly performed on in vitro models, presumably due to a lack of non-invasive in vivo methods. To date, it is not clear whether in vitro models are suitable to reflect the in vivo conditions for percutaneous penetration. Apart from inter and intraspecies skin differences, the excision of a skin sample may influence the penetration rate inter alia as a result of the contraction of the elastic fibres in the skin during excision. Therefore, the aim of the present study was to investigate the follicular reservoir of the hair follicles of human skin in vivo and in vitro utilizing the method of differential stripping. The results obtained revealed a significantly reduced follicular reservoir in vitro, which was only 9.5+/-10.6% of the in vivo reservoir. These results are important for the interpretation of earlier and future penetration investigations. It can thus be assumed that excised skin models are suitable for penetration studies only to a limited extent, as follicular penetration is greatly diminished due to the contraction of the elastic fibres of the skin.


Opposing regulation of Sox2 by cell-cycle effectors E2f3a and E2f3b in neural stem cells.
The mechanisms through which cell-cycle control and cell-fate decisions are coordinated in proliferating stem cell populations are largely unknown. Here, we show that E2f3 isoforms, which control cell-cycle progression in cooperation with the retinoblastoma protein (pRb), have critical effects during developmental and adult neurogenesis. Loss of either E2f3 isoform disrupts Sox2 gene regulation and the balance between precursor maintenance and differentiation in the developing cortex. Both isoforms target the Sox2 locus to maintain baseline levels of Sox2 expression but antagonistically regulate Sox2 levels to instruct fate choices. E2f3-mediated regulation of Sox2 and precursor cell fate extends to the adult brain, where E2f3a loss results in defects in hippocampal neurogenesis and memory formation. Our results demonstrate a mechanism by which E2f3a and E2f3b differentially regulate Sox2 dosage in neural precursors, a finding that may have broad implications for the regulation of diverse stem cell populations.


Specific angiotensin II binding sites in the rat stellate and superior cervical ganglia.
Angiotensin II binding sites were localized and quantified in rat stellate and superior cervical ganglia by quantitative autoradiography using 125I-Sar1-angiotensin II as a ligand. Both ganglia possess a single class of angiotensin II binding sites. High concentrations of binding sites were localized in the areas rich in principal ganglion cells. These binding sites might mediate the facilitatory action of angiotensin II on the ganglionic transmission.


Impact of delay in the diagnosis and treatment of head and neck cancer.
Head and neck tumors can be easily recognized through clinical evaluation. However, they are often diagnosed at advanced stages. To evaluate the delay from the patient's initial symptoms to the definitive treatment. Retrospective study of patients enrolled in 2011 and 2012. A questionnaire was filled in about socioeconomic aspects, patient history, tumor data, professionals who evaluated the patients, and the respective time delays. The following time delay medians were observed: ten months between symptom onset and the first consultation; four weeks between the latter and the first consultation with a specialist; four weeks between the specialist consultation and diagnosis attainment; and 12 weeks between diagnosis and the start of treatment. Most head and neck tumors are diagnosed at advanced stages, due to patient and health care factors.


A rare case of emphysematous pyelonephritis caused by Candida parapsilosis and Finegoldia magna complicated by medical care avoidance.
Emphysematous pyelonephritis (EPN) is a necrotizing gas producing infection of the renal parenchyma that commonly occurs in patients with diabetes. EPN requires early diagnosis and treatment due to the possible life-threatening septic complications. We report a rare case of EPN caused by an unfavorable mixed infection of Candida parapsilosis and Finegoldia magna. To our knowledge, this is the first reported case of EPN caused by Finegoldia magna. A 62-year-old male with diabetes mellitus (DM) presented with abdominal pain, shortness of breath, and nausea in which a diagnosis of septic shock was made due to EPN. Our patient first noticed abdominal pain 3 weeks prior to hospital presentation; however, he avoided getting treatment due to a fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This patient exhibited deterioration and expired after surgical intervention despite uneventful nephrectomy. This case suggests that medical care avoidance behaviors among patients could potentially complicate their clinical course.


Role of creatine kinase in cardiac excitation-contraction coupling: studies in creatine kinase-deficient mice.
To understand the role of creatine kinase (CK) in cardiac excitation-contraction coupling, CK-deficient mice (CK-/-) were studied in vitro and in vivo. In skinned fibers, the kinetics of caffeine-induced release of Ca2+ was markedly slowed in CK-/- mice with a partial restoration when glycolytic substrates were added. These abnormalities were almost compensated for at the cellular level: the responses of Ca2+ transient and cell shortening to an increased pacing rate from 1 Hz to 4 Hz were normal with a normal post-rest potentiation of shortening. However, the post-rest potentiation of the Ca2+ transient was absent and the cellular contractile response to isoprenaline was decreased in CK-/- mice. In vivo, echocardiographically determined cardiac function was normal at rest but the response to isoprenaline was blunted in CK-/- mice. Previously described compensatory pathways (glycolytic pathway and closer sarcoplasmic reticulum-mitochondria interactions) allow a quasi-normal SR function in isolated cells and a normal basal in vivo ventricular function, but are not sufficient to cope with a large and rapid increase in energy demand produced by beta-adrenergic stimulation. This shows the specific role of CK in excitation-contraction coupling in cardiac muscle that cannot be compensated for by other pathways.


[Culture and susceptibility testing of mycobacteria with VersaTREK].
Our laboratory of microbiology use the VersaTREK/ESP Culture System II for the isolation of mycobacteria. In this study, we evaluate this system for the analysis carried out between April 2009 and March 2010. The Myco bottles are supplemented with growth supplements and an antimicrobial agent solution prior to inoculation with the specimen. The technology of the VersaTREK/ESP Culture System II is based on the detection of headspace pressure changes within a sealed bottle. It monitors changes in either gas production or gas consumption due to microbial growth. A special algorithm has been developed for detection of very slow growing mycobacteria. The bottles are incubated during 42 days. Meanwhile a solid medium is inoculated too. All specimen types can be analysed with this system. Compared to solid culture, the time needed for detection of positive cultures was significantly shorter for the VersaTREK with a good recovery rate. For isolates recovered in both systems, mean time of detection is respectively 19.1 and 35.6 days for liquid and solid cultures. Mycobacteria identification may be determined using nucleic acid probs directly in Myco VersaTREK or in the solid medium. The susceptibility test of Mycobacteria tuberculosis complex is obtained between six and 13 days for rifampin, isoniazid, ethambutol, streptomycin and pyrasinamide. This system offers a faster diagnosis and is an alternative to other instruments using liquid culture.


Physical beneficiation of heavy minerals - Part 1: A state of the art literature review on gravity concentration techniques.
The efficiency of physical separation techniques of heavy minerals usually encounters some set-backs. The reason is often not far from the inability to develop suitable mineral characterization strategies in order to comprehend/evaluate certain physicochemical features such as surface chemistry, specific gravity difference, magnetic and electrical responses distributed among the mineral particles. The intense need for the development/advancement of efficient gravity concentration route on heavy minerals, more especially for the recovery and upgrade of fine, near-dense, low-grade heavy mineral deposits cannot be over-emphasized. However, the process application of gravity concentration on heavy minerals has not been widely investigated, and has often times been neglected. Existing literature on investigations conducted does not completely incorporate process routes, operating principles, parameters and applications; and as such, information in this area is somewhat scanty, hence the purpose of this study. A bulk of more recently developed gravity concentration medium such as enhanced gravity concentrations possess essential potentials which can be applied in certain physical beneficiation routes. On this premise, the need for further investigation is highly imperative. This review is therefore aimed at revealing the advantageous features of enhanced gravity concentrations over the conventional techniques, as well as the process selection for optimal beneficiation and high-grade yields. Thus, process applications, operating mechanism/principles, general performance evaluation in treating/upgrading heavy minerals using gravity techniques, the merits/shortcomings involved in conventional/enhanced gravity concentrators and recommendations have been captured in this review. This study will thus contribute greatly to the body of knowledge in the physical treatment/concentration of heavy minerals.


Multidimensional gas chromatography for the detailed PIONA analysis of heavy naphtha: hyphenation of an olefin trap to comprehensive two-dimensional gas chromatography.
A multidimensional method providing the composition of a heavy naphtha in paraffins, isoparaffins, olefins, naphthenes, and aromatics (PIONA) in the C8-C14 range is presented. The analytical set-up consists in a silver modified silica olefin trap on-line coupled to comprehensive two-dimensional gas chromatography (GC x GC). In this configuration, hydrocarbons are separated, in gaseous state, in two fractions, saturate and unsaturate, each fraction being subsequently analysed by GC or by GC x GC. The resolution between saturates and olefins was found to be improved compared to a single GC x GC run. The characterisation of the olefin trap highlights the benefits and the limits related to the use of that stationary phase as a double bond selective fractionation medium.


The morphology of ascending aortic aneurysms.
To determine the frequency of morphologic abnormalities of the aorta, especially of the media, in patients with aneurysms of the ascending aorta, tissue specimens from surgically resected ascending aortic aneurysms of 339 patients were studied. Included were 232 men and 107 women; 53 (29 men, 23 women) had clinical signs of Marfan's disease. Features evaluated and graded included fragmentation of elastic fibers, cystic medial change, medial fibrosis, medial necrosis, atherosclerosis, periaortic fibrosis, and thickening of the vasa vasorum. Both elastic fragmentation and cystic medial change were present in a high percentage of patients. Cystic medial change was inversely correlated with increasing age of patients, especially in the group of patients without clinical evidence of Marfan's syndrome. Marked changes of these types in many younger patients without Marfan's syndrome could reflect a "tissue insufficiency" in early life that causes the aortic wall to weaken and dilate. Medial necrosis, fibrosis, and atherosclerosis were directly correlated with age. Hemodynamic events are considered to initiate injury and repair within the aortic wall. Dissection was more frequently seen with medial abnormalities than with atherosclerosis.


Perspectives in weight control in diabetes - BI 456906.
Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved treatments for Type 2 diabetes mellitus, with liraglutide and semaglutide also approved for the treatment of obesity. The natural gut hormone oxyntomodulin is a weak dual agonist of the glucagon receptor (GCGR) and GLP-1R. Development of poly-agonists mimicking oxyntomodulin, such as the novel dual GCGR/GLP-1R agonist BI 456906, represents an important step towards a more effective treatment for people with Type 2 diabetes mellitus and obesity. BI 456906 is a 29-amino acid peptide derived from glucagon, with the incorporation of potent GLP-1 activities. It contains a C18 diacid which mediates binding to albumin, thereby prolonging the half-life to enable once-weekly subcutaneous dosing. The utilisation of GCGR agonism aims to enhance body weight-lowering effects by increasing energy expenditure in addition to the anorectic action of GLP-1R agonists. Glucose-lowering efficacy of BI 456906 has been demonstrated in a Phase II trial in patients with Type 2 diabetes mellitus and obesity and was associated with clinically meaningful body weight loss. These data highlight the potential of dual GCGR/GLP-1R agonism for reducing glycated haemoglobin and body weight in patients with Type 2 diabetes mellitus, and for greater therapeutic efficacy compared with GLP-1R agonism alone.


The low-density lipoprotein receptor-related protein associates with calnexin, calreticulin, and protein disulfide isomerase in receptor-associated-protein-deficient fibroblasts.
The low-density lipoprotein receptor-related protein (LRP) is a large (>600 kDa) multi-ligand-binding cell surface receptor that is now known to participate in a diverse range of cellular events. To accomplish this diverse role, LRP is composed of repetitive amino acid motifs consisting of complement-type and EGF precursor-type repeats. Within these repeats are six conserved cysteine residues that form the core disulfide bond structure of each repeat. To accommodate the intricate folding that such a complex structure dictates, a specialized chaperone is present in the endoplasmic reticulum (ER) called the receptor-associated protein (RAP) that binds to LRP immediately following its biosynthesis and assists in its exocytic transport. Interestingly, RAP -/- mice show reduced LRP expression in certain cell types, but not a more global affect on LRP expression that was expected. Such a tissue-restricted effect by RAP prompted an investigation if other ER chaperones associate with LRP to assist in its complex folding requirements and compensate for the absence of RAP in RAP -/- cells. Fibroblasts obtained from RAP -/- mice demonstrate similar LRP expression levels and subcellular distribution as RAP +/+ fibroblasts. Moreover, RAP -/- cells show an identical exocytic trafficking rate for LRP as RAP +/+ cells and comparable cell surface internalization kinetics. In RAP -/- cells, three well-known ER chaperones, calnexin, calreticulin, and protein disulfide isomerase (PDI), associate with LRP and likely compensate for the absence of RAP.


Short-term prophylaxis with cefotaxime in colorectal surgery. A prospective, randomized trial.
In a controlled, randomized study the effect of penicillin and streptomycin on postoperative septic complications in colorectal surgery (penicillin, 2 ml, IU, intramuscularly, three times daily for a period of six days and concomitantly streptomycin, 0.5 gm, intramuscularly, two times daily for a period of four days) was compared with the effect of cefotaxime, 2 gm, intravenously, three times on the day of surgery. One hundred patients completed the study: 48 were treated with penicillin and streptomycin (Group 1) and 52 with cefotaxime (Group 2). Wound infection occurred in one patient (2.1 percent) in Group 1, but not in Group 2 (0%, N.S.). Rupture of the wound occurred in one patient in each group (2.1 percent vs. 1.9 percent, N.S.). Insufficiency of the anastomosis occurred in four patients in Group 1 (8.3 percent) and in one patient in Group 2 (1.9 percent). It is concluded that short-term prophylaxis with cefotaxime is as effective as long-term prophylaxis with penicillin and streptomycin.


ILCs and Allergy.
The recent discovery of new innate lymphoid cells (ILCs) has revolutionized the field of allergies. Since most allergic diseases induce a type 2 immune response, Th2 cells, which produce IL-4, IL-5, and IL-13 in an antigen-dependent manner, in addition to basophils and mast cells which are activated by antigen-specific IgE, are thought to play a major role in the pathogenesis. However, since group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines (i.e., IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, GM-CSF, and amphiregulin) in response to various cytokines, including IL-33 in the surrounding environment, the possibility has emerged that there are two types of allergies: allergies induced in an antigen-dependent manner by Th2 cells and allergies induced in an antigen-independent manner by ILC2s. In order to make an impact on the increasing incidence of allergic diseases in the world, it is essential to research and develop new treatments that focus not only on Th2 cells but also on ILC2s. In this chapter, the role of ILCs in allergic diseases, which has rapidly changed with the discovery of ILCs, is discussed, focusing mainly on ILC2s.


DNA metabarcoding and morphological macroinvertebrate metrics reveal the same changes in boreal watersheds across an environmental gradient.
Cost-effective, ecologically relevant, sensitive, and standardized indicators are requisites of biomonitoring. DNA metabarcoding of macroinvertebrate communities is a potentially transformative biomonitoring technique that can reduce cost and time constraints while providing information-rich, high resolution taxonomic data for the assessment of watershed condition. Here, we assess the utility of DNA metabarcoding to provide aquatic indicator data for evaluation of forested watershed condition across Canadian eastern boreal watersheds, subject to natural variation and low-intensity harvest management. We do this by comparing the similarity of DNA metabarcoding and morphologically derived macroinvertebrate metrics (i.e. richness, % Ephemeroptera, Plecoptera and Trichoptera, % chironomid), and the ability of DNA metabarcoding and morphological metrics to detect key gradients in stream condition linked to forested watershed features. Our results show consistency between methods, where common DNA metabarcoding and morphological macroinvertebrate metrics are positively correlated and indicate the same key gradients in stream condition (i.e. dissolved oxygen, and dissolved organic carbon, total nitrogen and conductivity) linked to watershed size and shifts in forest composition across watersheds. Our study demonstrates the potential usefulness of macroinvertebrate DNA metabarcoding to future application in broad-scale biomonitoring of watershed condition across environmental gradients.


In-depth proteomic analysis of shell matrix proteins of Pinctada fucata.
The shells of pearl oysters, Pinctada fucata, are composed of calcite and aragonite and possess remarkable mechanical properties. These shells are formed under the regulation of macromolecules, especially shell matrix proteins (SMPs). Identification of diverse SMPs will lay a foundation for understanding biomineralization process. Here, we identified 72 unique SMPs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of proteins extracted from the shells of P. fucata combined with a draft genome. Of 72 SMPs, 17 SMPs are related to both the prismatic and nacreous layers. Moreover, according to the diverse domains found in the SMPs, we hypothesize that in addition to controlling CaCO3 crystallization and crystal organization, these proteins may potentially regulate the extracellular microenvironment and communicate between cells and the extracellular matrix (ECM). Immunohistological localization techniques identify the SMPs in the mantle, shells and synthetic calcite. Together, these proteomic data increase the repertoires of the shell matrix proteins in P. fucata and suggest that shell formation in P. fucata may involve tight regulation of cellular activities and the extracellular microenvironment.


5-HT6 receptors and Alzheimer's disease.
During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease.


Effects of mineral additives on antibiotic resistance genes and related mechanisms during chicken manure composting.
In this study, two typical minerals (diatomite and bentonite) were applied during composting, and their influences on antibiotics, antibiotic resistance genes (ARGs), intI1 and the bacterial communities were investigated. The relative abundance of total ARGs decreased by 53.72% and 59.54% in diatomite and bentonite addition compared with control on day 42. The minerals addition also reduced the relative abundance of intI1, as much as 41.41% and 59.81% in diatomite and bentonite treatments. Proteobacteria and Firmicutes were the dominant candidate hosts of the major ARGs. There was a significant correlation between total ARGs and intI1 during the composting. Structural equation models further demonstrated that intI1 and antibiotics were the predominant direct factors responsible for ARG variations, and composting properties and bacterial community composition also shifted the variation of ARG profiles by influencing intI1. Overall, these findings suggest that diatomite and bentonite could decrease the potential proliferation of ARGs in chicken manure.


A succinylcholine-like action of an Ipomoea carnea Jacq subsp. fistulosa (Mart. ex choisy) extract.
An aqueous alcoholic extract of Ipomoea carnea subsp. fistulosa was tested in vitro on isolated preparations of the frog rectus abdominis muscle and the rabbit perfused heart as well as in vivo in the chicken. The extract and succinylcholine (suxamethonium) contracted the frog rectus abdominis muscle and this action was blocked by tubocurarine, 1.5 micrograms/ml. Both extract and succinylcholine produced bradycardia of the rabbit heart which was antagonized by atropine, 20 micrograms/ml. Like succinylcholine, the extract produced spastic paralysis in chickens. It is suggested that the extract possesses a depolarizing action similar to that of succinylcholine.


Observations on the history of non-insect invertebrate pathology from the perspective of a participant.
This paper discusses diseases of commercially important non-insect invertebrates from both a historical and a personal perspective. Early studies of curious scientists such as Metchnikoff using invertebrate systems led to important discoveries with much wider impact. As commercial culture of oysters, shrimp, and other invertebrates grew, so did studies of their diseases. Here, the impact of pioneering scientists and important new techniques on our understanding of these diseases is described.


Shigella spp. and enteroinvasive Escherichia coli pathogenicity factors.
Bacteria of Shigella spp. (S. boydii, S. dysenteriae, S. flexneri and S. sonnei) and enteroinvasive Escherichia coli (EIEC) are responsible for shigellosis in humans, a disease characterized by the destruction of the colonic mucosa that is induced upon bacterial invasion. Shigella spp. and EIEC strains contain a virulence plasmid of approximately 220 kb that encodes determinants for entry into epithelial cells and dissemination from cell to cell. This review presents the current model on mechanisms of invasion of the colonic epithelium by these bacteria and focuses on their pathogenicity factors, particularly the virulence plasmid-encoded type III secretion system.


Individualized fludarabine-based regimen in elderly patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.
The aim of this study was to investigate the efficacy and safety of a fludarabine-based individualized regimen in elderly patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Sixteen patients were treated with the individual regimen of fludarabine combined with rituximab. Adverse reactions and efficacy of treatment were observed. Sixteen patients received a total of 69 courses of immunochemotherapy, with an average administration of 275 mg fludarabine per person. The overall response rate was 81.3% (13/16), in which seven cases (43.8%) achieved complete remission, six cases (37.5%) achieved partial remission, two cases (12.5%) had stable disease, and one case (6.3%) developed disease progression. The most frequent side effect was myelosuppression. Two patients experienced grade 3-4 cytopenia, one case developed a grade 3 infection, and no treatment-related death was observed. The individual regimen of fludarabine combined with rituximab demonstrated marked clinical efficacy and acceptable toxicity in elderly patients with CLL/SLL.


Technique of recanalization of long-segment flush superior mesenteric artery occlusions.
To describe technical tips for recanalization of long-segment flush superior mesenteric artery (SMA) occlusions. Ultrasound-guided left brachial artery access was gained in 2 patients with a 7F 90-cm sheath being advanced to the supraceliac aorta. The SMA stump was visualized using a selective inferior mesenteric artery (IMA) catheterization via femoral approach. A combination of a 7F 100-cm Multipurpose (MPA) guide and a 5F 125-cm MPA catheter was utilized to provide support for selective catheterization. Subsequently, a 0.018-inch wire and catheter were advanced crossing the area of occlusion. Predilatation was performed, followed by placement of covered stent. Both patients had uncomplicated course and resolution of symptoms. Flush SMA occlusions are challenging lesions but may be treated by antegrade percutaneous recanalization with good results. Technical aspects that facilitate recanalization include brachial approach, use of a stiff system (sheath, guide, and catheter) and concomitant injection to facilitate visualization of the SMA stump.


Pancytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis.
Low dose pulse MTX was associated with the development of pancytopenia in six patients with RA. Two patients died. Factors implicated in the occurrence of this complication were renal impairment in five patients, medication errors by two patients, preexisting marrow injury from occult alcoholism in one patient, and an apparent idiosyncratic reaction to the drug in another. Medication errors were associated with the use of five or more medications, and the unusual schedule of administration of low dose MTX may also have been contributory. From a consideration of the clinical pharmacokinetics of MTX, we suggest other factors that may predispose to the occurrence of marrow toxicity: the presence of hypoalbuminemia, interactions between MTX and other protein bound or weakly acidic drugs, and the repetitive dosing schedule of low dose MTX. Based on our experience, patients with impaired renal function (creatinine greater than or equal to 2.0 mg/dL) should not receive MTX. Renal function should be monitored regularly during treatment with MTX, and blood counts should be observed carefully if a new drug is added or substituted. A 5 mg test dose of MTX before initiating weekly therapy may identify patients with severe hypersensitivity to the drug. The potential risks of using MTX in a patient unwilling to accept blood products should be acknowledged and discussed with the patient. Furthermore, we recommend the use of leucovorin if pancytopenia occurs, even if low or undetectable serum levels of MTX are present.


Involvement of Na+/K+ pump in fine modulation of bursting activity of the snail Br neuron by 10 mT static magnetic field.
The spontaneously active Br neuron from the brain-subesophageal ganglion complex of the garden snail Helix pomatia rhythmically generates regular bursts of action potentials with quiescent intervals accompanied by slow oscillations of membrane potential. We examined the involvement of the Na(+)/K(+) pump in modulating its bursting activity by applying a static magnetic field. Whole snail brains and Br neuron were exposed to the 10-mT static magnetic field for 15 min. Biochemical data showed that Na(+)/K(+)-ATPase activity increased almost twofold after exposure of snail brains to the static magnetic field. Similarly, (31)P NMR data revealed a trend of increasing ATP consumption and increase in intracellular pH mediated by the Na(+)/H(+) exchanger in snail brains exposed to the static magnetic field. Importantly, current clamp recordings from the Br neuron confirmed the increase in activity of the Na(+)/K(+) pump after exposure to the static magnetic field, as the magnitude of ouabain's effect measured on the membrane resting potential, action potential, and interspike interval duration was higher in neurons exposed to the magnetic field. Metabolic pathways through which the magnetic field influenced the Na(+)/K(+) pump could involve phosphorylation and dephosphorylation, as blocking these processes abolished the effect of the static magnetic field.


Murine thymocytes possess specific cell surface-associated exoaminopeptidase activities: preferential expression by immature CD4-CD8- subpopulation.
Murine thymocytes are shown to possess at least three well-defined exo-N-aminopeptidase activities on their surface. One of them cleaves the prolyl bond in the synthetic dipeptide nitroanilide Gly-Pro-pNA (Km 0.95 mM and Vmax 8 nmol/h at pH 7.4 and 37 degrees C) and is specifically inhibited by phenylmethane sulfonyl fluoride, diprotin A, Gly-Pro-Ala and Gly-Pro-Gly-Gly. These data further support identification of this enzyme with a serine exopeptidase dipeptidyl peptidase IV (DPP IV), previously reported to be specific for collagen. The two other forms of N-exopeptidase activities are detected when Ala-pNA and Leu-pNA are used as substrates. Leu-aminopeptidase activity (Km 1.4 mM, Vmax 15 nmol/h) and Ala-aminopeptidase activity (Km 4.0 mM, Vmax 20 nmol/h) are inhibited by inhibitors for thiol- and trypsin-like proteinases, i.e. tosyl lysyl chloromethyl ketone, leupeptin and N-ethylmaleimide. Addition inhibition of Leu-aminopeptidase activity by peptstatin, a known inhibitor of carboxyl proteases, suggests that aminopeptidase activity detected with Leu-pNA is different in part from Ala-aminopeptidase activity. Among the various lymphoid cell populations tested, the three aminopeptidase activities are increased by three- to fourfold in the immature CD4-CD8- thymocyte subset as well as in the thymoma BW5147. In contrast, cortisone-resistant thymocytes, lymph node and spleen cells exhibit levels of activities almost similar to that of unfractionated thymocytes. During ontogeny, the levels of these activities are increased four- to sevenfold on fetal thymocytes (from days 14 to 16). Finally, when thymocytes or spleen cells are cultured with a mitogenic concentration of concanavalin A, their proliferative responses are correlated with an enhancement of the aminopeptidase activities (1.3- to 5-fold). From these results, a correlation between the presence of these peptidases on the cell surface of immature and mature lymphoid cells and biological responsiveness is suggested.


The effect of 8-methoxypsoralen-plus ultraviolet light on cell-virus interaction: the transforming infection; effect of PUVA on the transformation of baby hamster kidney cells by polyoma virus.
Pre-treatment of baby hamster kidney (BHK) cells with 8-methoxypsoralen (8-MOP) plus ultraviolet (UV) light enhances the frequency of their transformation by polyoma (Py) virus. Of the doses tested, 0.5 microgram/ml 8-MOP plus 0.3 J/cm2 UV-light results in maximal (30-fold) stimulation of viral transformation. 8-MOP alone does not affect viral transformation and UV-light alone causes only a slight increase in the transformation frequency. Thus the drug and light act synergistically in promoting the effect. Treatment of BHK cells with drug plus light without Py infection does not lead to a transformed morphology. A drug-light combination (0.01 microgram/ml 8-MOP plus 1.2 J/cm2 UV) that inhibits cellular DNA synthesis to 75% of control at 28 hr after treatment results in a 6-fold stimulation of the transformation frequency.


Effect of thin carbonate-containing apatite (CA) coating of titanium fiber mesh on trabecular bone response.
The influence of thin carbonate-containing apatite (CA) coating on trabecular bone response to cylindrical titanium fiber mesh (porosity of 85%, pore size of 200-300 microm, 2.8 mm diameter x 6 mm length) implants was investigated. Thin CA coatings were deposited by the so-called molecular precursor method. Molecular precursor solution was obtained by adding dibutylammonium diphosphate salt to Ca-EDTA/amine ethanol solution by adjusting Ca/P = 1.67. Sintered cylindrical titanium fiber mesh was immersed into molecular precursor solution and then tempered at 600 degrees C for 2 h. The immersion and tempering process was repeated three times. An adherent thin CA film could be deposited on the inside of titanium fiber mesh. After the immersion of a CA-coated titanium fiber mesh in simulated body fluid, apatite crystals precipitated on the titanium fiber mesh. Uncoated and CA-coated titanium fiber mesh was inserted into the trabecular bone of the left and right femoral condyles of rabbits. Histological and histomorphometrical evaluation revealed a significantly greater amount of bone formation inside the porous area of the CA-coated titanium fiber mesh after 12 weeks of implantation. The present results suggested that a thin CA-coated titanium mesh has better osteoconductivity and will be useful for a three-dimensional scaffold.


BRUCH MEMBRANE RUPTURE AND CHOROIDAL NEOVASCULARIZATION COMPLICATING EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE: A CASE REPORT.
To describe a case of extensive macular atrophy with pseudodrusen-like appearance complicated by Bruch membrane rupture and choroidal neovascularization, treated with intravitreal injection of an antivascular endothelial growth factor drug. A 54-year-old woman, affected by extensive macular atrophy with pseudodrusen-like appearance, has developed Bruch membrane rupture and choroidal neovascularization. This report discusses the development of the disease and the improvement after a single intravitreal injection of Avastin. After treatment, the visual acuity increased from 20/400 to 20/200; clinical and anatomical improvement remained stable with a 2-month follow-up. Extensive macular atrophy with pseudodrusen-like appearance could be complicated by Bruch membrane rupture and subsequent choroidal neovascularization. Antivascular endothelial growth factor intravitreal injection could have beneficial effects on this entity, but concern could raise in respect of possible increase of chorioretinal atrophy.


The Risk of Vocal Fold Atrophy after Serial Corticosteroid Injections of the Vocal Fold.
The aim of this study was to illustrate the risk of vocal fold atrophy in patients who receive serial subepithelial steroid injections for vocal fold scar. This study is a retrospective case report of two patients who underwent a series of weekly subepithelial infusions of 10 mg/mL dexamethasone for benign vocal fold lesion. Shortly after the procedures, both patients developed a weak and breathy voice. The first patient was a 53-year-old man with radiation-induced vocal fold stiffness. Six injections were performed unilaterally, and 1 week later, he developed unilateral vocal fold atrophy with new glottal insufficiency. The second patient was a 67-year-old woman with severe vocal fold inflammation related to laryngitis and calcinosis, Raynaud's phenomenon, esophagean dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. Five injections were performed bilaterally, and 1 week later, she developed bilateral vocal fold atrophy with a large midline glottal gap during phonation. In both cases, the steroid-induced vocal atrophy resolved spontaneously after 4 months. Serial subepithelial steroid infusions of the vocal folds, although safe in the majority of patients, carry the risk of causing temporary vocal fold atrophy when given at short intervals.


Long-term quality of life and symptoms of patients who underwent esophageal reconstruction employing intestinal pedicle grafts.
This study was conducted to assess the long-term quality of life (QOL) and symptoms experienced by patients who underwent esophageal reconstruction. We invited by mail 64 patients (group 1) and 400 subjects from the general population (group 2) to complete a two-part questionnaire regarding esophageal function and QOL (RAND 36). In all 39 group 1 and 114 group 2 subjects qualified for the final analysis. In the majority esophageal symptoms appeared directly after the operation. Symptoms of problems were choking (51%), burp (38%), and postprandial fullness (36%). Nineteen patients (49%) reported other comorbidities. Group 1 reported poorer QOL (P <0.01) in 2 of 8 QOL areas by comparision with group 2. There were no correlations between QOL scales and type of intestinal pedicle grafts or time after esophageal reconstruction. Long-term QOL assessed by the patients themselves in general seems to be similar to that of the control sample. Combining a QOL survey with an esophageal module makes this instrument more specific.


Rhabdoid tumours of the central nervous system. Report of three cases with immunocytochemical and ultrastructural findings.
Three cases of rhabdoid tumour of the central nervous system arising in a supratentorial location are reported. The patients were 18, 14, and 7 years old. All three tumours showed a common morphology. The neoplastic cells were usually globoid with round nuclei and prominent nucleoli and large acidophilic, cytoplasmic inclusions were present in many of them. These inclusions showed strong immunoreactivity for vimentin, weak immunoreactivity for epithelial membrane antigen and focal immunoreactivity for cytokeratins. Ultrastructurally they were made up of whorls of intermediate filaments, 8-10 nm in thickness. Rhabdoid tumours of the central nervous system, whatever the cell of origin, appear to be an independent entity with identifiable histology and aggressive behaviour.


Formation of N-nitrosodimethylamine (NDMA) from reaction of monochloramine: a new disinfection by-product.
Studies have been conducted specifically to investigate the hypothesis that N-nitrosodimethylamine (NDMA) can be produced by reactions involving monochloramine. Experiments were conducted using dimethylamine (DMA) as a model precursor. NDMA was formed from the reaction between DMA and monochloramine indicating that it should be considered a potential disinfection by-product. The formation of NDMA increased with increased monochloramine concentration and showed maximum in yield when DMA was varied at fixed monochloramine concentrations. The mass spectra of the NDMA formed from DMA and 15N isotope labeled monochloramine (15NH2Cl) showed that the source of one of the nitrogen atoms in the nitroso group in NDMA was from monochloramine. Addition of 0.05 and 0.5 mM of preformed monochloramine to a secondarily treated wastewater at pH 7.2 also resulted in the formation of 3.6 and 111 ng/L of NDMA, respectively, showing that this is indeed an environmentally relevant NDMA formation pathway. The proposed NDMA formation mechanism consists of (i) the formation of 1,1-dimethylhydrazine (UDMH) intermediate from the reaction of DMA with monochloramine followed by, (ii) the oxidation of UDMH by monochloramine to NDMA, and (iii) the reversible chlorine transfer reaction between monochloramine and DMA which is parallel to (i). We conclude that reactions involving monochloramine in addition to classical nitrosation reactions are potentially important pathways for NDMA formation.


Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma.
We describe three patients from a family with motor and sensory neuropathy accompanied by open-angle glaucoma. Autosomal recessive demyelinating hereditary motor and sensory neuropathies (HMSN) include different disorders. To our knowledge, autosomal recessive HMSN has not been associated with juvenile onset glaucoma. Sural nerve pathology of the three patients were examined, and genetic analysis of the family was performed. - The most prominent pathologic finding was a highly unusual myelin abnormality consisting of irregular redundant loops and folding of the myelin sheath. The family survey supports autosomal recessive inheritance. The molecular analysis failed to demonstrate either linkage of the disease to MPZ gene, PMP22 gene, Cx32 gene, orEGR2 gene. Analysis did not establish linkage of the disease to the locus of CMT4A, 4B, and 4C genes. The present cases may represent a new type of HMSN accompanied by juvenile onset glaucoma.


Abnormal extension of the big toe as a cause of ulceration in diabetic feet.
Relief from external pressure and repetitive stress is a main concept in treating diabetic neuropathic ulcers. Ulcers on the tip of the big toe may be caused by abnormal extension of the big toe, which can be diagnosed only by observing the patient during barefoot walking. A flexor pad underneath the big toe eliminates the phenomenon, but in case of rigidity of the toe, extremely roomy toe boxes must be prescribed. Out of a series of 272 diabetic patients with skin lesions on the feet 18 suffered this phenomenon, in one case with bilateral ulcerations. Fifteen ulcers healed and below the knee amputation had to be carried out in 4 legs due to ischaemia.


Structure elucidation, biogenesis, and bioactivities of acylphloroglucinol-derived meroterpenoid enantiomers from Dryopteris crassirhizoma.
Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 ∼ 10, 13, 14, and 17 ∼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 ∼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (±1/±2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1β, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1).


In vitro fertilization outcomes after fresh and frozen blastocyst transfer in South Asian compared with Caucasian women.
To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles. Retrospective cohort study. Not applicable. Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014. Not applicable. Live birth rate. A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%). Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET.


Transposons in place of telomeric repeats at a Drosophila telomere.
We present the first isolation of the terminal DNA of an intact Drosophila telomere. It differs from those isolated from other eukaryotes by the lack of short tandem repeats at the terminus. The terminal 14.5 kb is composed of four tandem elements derived from two families of non-long terminal repeat retrotransposons and is subject to slow terminal loss. One of these transposon families, TART (telomere-associated retrotransposon), is described for the first time here. The other element, HeT-A, has previously been shown to transpose to broken chromosome ends. Our results provide key evidence that these elements also transpose to natural chromosome ends. We propose that the telomere-associated repetitive DNA is maintained by saltatory expansions, including terminal transpositions of specialized retrotransposons, which serve to balance terminal loss.


The Impact of 1 Year of Healthier School Food Policies on Students' Diets During and Outside of the School Day.
In 2012, Massachusetts implemented both the updated national school meal standards and comprehensive competitive food/beverage standards that closely align with current national requirements for school snacks. This study examines the impact of these combined standards on school meal and snack food selections, as well as food choices outside of school. In addition, this study examines the impact of these standards on nutrients consumed. The NOURISH (Nutrition Opportunities to Understand Reforms Involving Student Health) Study was an observational cohort study conducted among students from spring 2012 to spring 2013. One hundred sixty students in 12 middle schools and high schools in Massachusetts completed two 24-hour recalls before (spring 2012) and after implementation (spring 2013) of the updated standards. Changes in school meals, competitive food, and after-school snack selection, as well as nutrients consumed outside of school were examined. Logistic regression and mixed-model analysis of variance were used to examine food selection and consumption. After implementation, 13.6% more students chose a school meal (70.1% vs 56.5%; P=0.02). There were no differences in competitive food purchases but a significant decrease in the number of after-school unhealthy snacks consumed (0.69 [standard error=0.08] vs 1.02 [standard error=0.10]; P=0.009). During the entire day, students consumed, on average, 22 fewer grams of sugar daily after implementation compared with before implementation (86 g vs 108 g; P=0.002). With the reduction in the number of unhealthy school snacks, significantly more students selected school meals. Students did not compensate for lack of unhealthy snacks in school by increased consumption of unhealthy snacks outside of school. This provides important new evidence that both national school meal and snack policies may improve daily diet quality and should remain strong.