CBS homogenization mutation strategy narrows the glycan binding profile of a GlcNAc-specific lectin AANL.
Glycosylation plays important roles in many cellular processes, such as signal transduction, cell cycle progression and transcriptional regulation. However, the identification and analysis of glycosylation are severely hampered by the low specificity or avidity of antiglycan antibodies and lectins. We have reported that a lectin AANL, which has high specificity for terminal GlcNAc glycans and contains six carbohydrate binding sites (CBSs), was used to enrich O-GlcNAcylated peptides. To further improve AANL binding specificity, we designed a CBS-homogenization strategy and restructured six mutant lectins, known as AANL1-AANL6. Affinity chromatography with GlcNAc and isothermal titration calorimetry analysis indicated that the two mutants (AANL3 and AANL6) all maintained GlcNAc binding activity. AANL6 and AANL3 showed higher specificity for terminal GlcNAc glycans than AANL, as shown by the hemagglutination assay, cell binding assays and glycan microarray analysis, and AANL6 exhibited the highest specificity. The binding activity of AANL6 for O-GlcNAcylated peptides was shown by surface plasmon resonance assays. By AANL6 affinity chromatography enrichment and mass spectrometry analysis, 79 high-confidence and 21 putative O-GlcNAcylated sites were identified on 85 peptides mapped onto 54 proteins. Most of these sites were new sites compared with reported data. These results indicate that the enrichment capacity of AANL6 is higher than that of wild-type AANL. In conclusion, the CBS-homogenization mutation strategy was successful, and AANL6 was identified as a powerful tool for O-GlcNAcylation enrichment. Our research suggests that the CBS-homogenization strategy is valuable for improving the specificity of lectins with multiple CBSs.


SARM1, an Enzyme Involved in Axon Degeneration, Catalyzes Multiple Activities through a Ternary Complex Mechanism.
Sterile alpha and toll/interleukin receptor (TIR) motif containing protein 1 (SARM1) is an NAD+ hydrolase and cyclase involved in axonal degeneration. In addition to NAD+ hydrolysis and cyclization, SARM1 catalyzes a base exchange reaction between nicotinic acid (NA) and NADP+ to generate NAADP, which is a potent calcium signaling molecule. Herein, we describe efforts to characterize the hydrolysis, cyclization, and base exchange activities of TIR-1, the Caenorhabditis elegans ortholog of SARM1; TIR-1 also catalyzes NAD(P)+ hydrolysis and/or cyclization and regulates axonal degeneration in worms. We show that the catalytic domain of TIR-1 undergoes a liquid-to-solid phase transition that regulates not only the hydrolysis and cyclization reactions but also the base exchange reaction. We define the substrate specificities of the reactions, demonstrate that cyclization and base exchange reactions occur within the same pH range, and establish that TIR-1 uses a ternary complex mechanism. Overall, our findings will aid drug discovery efforts and provide insight into the mechanism of recently described inhibitors.


Digital radiography reject analysis: data collection methodology, results, and recommendations from an in-depth investigation at two hospitals.
Reject analysis was performed on 288,000 computed radiography (CR) image records collected from a university hospital (UH) and a large community hospital (CH). Each record contains image information, such as body part and view position, exposure level, technologist identifier, and--if the image was rejected--the reason for rejection. Extensive database filtering was required to ensure the integrity of the reject-rate calculations. The reject rate for CR across all departments and across all exam types was 4.4% at UH and 4.9% at CH. The most frequently occurring exam types with reject rates of 8% or greater were found to be common to both institutions (skull/facial bones, shoulder, hip, spines, in-department chest, pelvis). Positioning errors and anatomy cutoff were the most frequently occurring reasons for rejection, accounting for 45% of rejects at CH and 56% at UH. Improper exposure was the next most frequently occurring reject reason (14% of rejects at CH and 13% at UH), followed by patient motion (11% of rejects at CH and 7% at UH). Chest exams were the most frequently performed exam at both institutions (26% at UH and 45% at CH) with half captured in-department and half captured using portable x-ray equipment. A ninefold greater reject rate was found for in-department (9%) versus portable chest exams (1%). Problems identified with the integrity of the data used for reject analysis can be mitigated in the future by objectifying quality assurance (QA) procedures and by standardizing the nomenclature and definitions for QA deficiencies.


[The effects of amiodarone on the thyroid].
Amiodarone is a drug widely used for the treatment of arrhythmias. In 16% of amiodarone-treated patients it causes changes in the thyroid function. The aim of this study was to determine the importance of amiodarone-induced thyroid dysfunction in the population of Navarre, studied between 2001 and 2007. We present a retrospective study that considers the characteristics of 182 amiodarone-treated patients with thyroid dysfunction who had been referred to our Institute. We determined a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid sonography and thyroid scintigraphy uptake). Screening of the thyroid function, recommended before starting amiodarone treatment, was carried out in only 20.9 % of the patients. Forty-one percent of patients developed amiodarone induced hypothyroidism; in 76% of them the drug was withdrawn. Hypothyroidism appears after 21 (+/- 12) months of amiodarone treatment. Forty-eight point six developed permanent hypothyroidism. This group of patients had higher serum levels of TSH (thyrotropin) and were treated for less time with amiodarone. Fifty-nine percent of patients developed amiodarone induced thyrotoxicosis; 59.4 % were diagnosed with thyrotoxicosis (AIT) type 1, 30.6% AIT type 2 and the remaining 10 % were diagnosed with mixed thyrotoxicosis. Thyrotoxicosis appears after 29.5 (+/- 17) months of amiodarone treatment. The serum levels of free thyroxine were significantly higher in the AIT type 2 than in the AIT type1. All patients were treated with antithyroid drugs and/or corticoids. Some patients were admitted to hospital due to the severity of their illness. In our study, amiodarone induced thyrotoxicosis was more frequent than hypothyroidism (59% vs 41%) because Navarre is an iodine-deficient area. It is necessary to control the thyroid function after 2-3 years of amiodarone treatment.


A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.
In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. In a prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum, and nonpregnant periods. Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower during pregnant compared with postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and nonpregnant periods (P = 0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared with nonpregnant periods. CD4 count declines among HIV-1-infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short-term impact on plasma HIV-1 RNA concentrations.


Patient evaluation of otolaryngology department service at Christchurch Hospital.
One hundred and four consecutive patients seen in the ENT department for consultation and inpatient treatment completed a structured questionnaire at their first postoperative (or posttreatment) outpatient clinic appointment. The aims of the survey were to ascertain the patients opinions and perceptions regarding the ENT department service in a variety of areas. Satisfaction was high in areas of medical and nursing care and with the information given regarding treatment. The major area of dissatisfaction was with waiting times, particularly waiting times at appointments during ENT outpatient clinics.


The growth of virulent African swine fever virus in pig monocytes and macrophages.
The replication of virulent African swine fever virus (ASFV) in cultures of monocytes and macrophages derived from pig bone marrow (PBM) and pig leukocyte (PL) cells was investigated by light microscopy, immunofluorescence, haemadsorption and infective virus release. Monocytes showed a high rate of infection and complete destruction within 2 to 3 days, whereas macrophages had only a very low level of infection and survived to form persistently infected cultures. These observations may explain the decrease in sensitivity of PBM and PL cells for ASFV assay after extended periods of incubation and suggest that the macrophage may be one of the cell types concerned with virus persistence in the pig.


Developmental changes in antioxidant enzymatic defences against oxidative stress in sheep placentomes.
Early pregnancy is susceptible to oxidative stress, and thus characterisation of antioxidant systems and pro- and anti-apoptotic pathways would improve understanding of placental development and function. We aimed, therefore, to determine the activities of the antioxidant enzymes, copper/zinc-superoxide dismutase (SOD1), manganese-SOD (SOD2), catalase (CAT), glutathione (GSH) peroxidase (GPX) and GSH reductase (GSR); and to quantify the expression of BAX and MCL1 proteins in relation to the developmental changes in antioxidant defences in sheep placentomes sampled on days 35, 55 and 80 of pregnancy. Placentome progesterone content was analyzed to determine steroidogenic capacity. Malondialdehyde (MDA) and protein carbonyl were quantified in placentomes as biomarkers of lipid peroxidation and protein damage respectively. Placentome tissues demonstrated significantly increased content of progesterone and MDA at day 80 of pregnancy and protein carbonyl as early as day 50 of pregnancy. Progesterone and MDA contents were not different between days 35 and 55 of pregnancy. While SOD1 and CAT activities did not alter significantly, SOD2 activity decreased from days 35 to 55. GPX activity increased from days 35 to 55 and increased further to day 80 of pregnancy. GSR activity increased from days 35 to 55 of pregnancy. BAX protein expression decreased, while MCL1 increased from days 35 to 55 and 80 of pregnancy. The increased GPX activity was associated with a decrease in the BAX/MCL1 protein expression ratio. Changes in the antioxidant enzymatic defences could be a part of placentome adaptation to reactive oxygen species-induced oxidative stress at specific early developmental stages of pregnancy.


Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells.
Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX-loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.


Giant cell tumor of the mobile spine: a review of 49 cases.
This is a retrospective review of 49 cases of giant cell tumor (GCT) of the mobile spine treated surgically. Our goal was to determine which factors influenced local recurrence. GCT is a benign, locally aggressive tumor that rarely occurs in the spine. The management of local recurrence can be challenging. We performed a retrospective analysis of GCTs of the mobile spine managed between 1970 and 2005. Median follow-up was 145 months with a minimum of 2 years or until death. We used the Kaplan-Meier method to test whether Enneking stage, surgery type, and surgical margin had statistically significant impact on local recurrence. The log rank test was used for comparison, and a P value of less than 0.05 was deemed significant. Of the 49 patients, 11 (22%) local recurrences occurred. The latest recurrence occurred at 60 months. Age less than 25 years was associated with a worse relapse-free survival (P = 0.03). En bloc resection was associated with better local control with Enneking stage III tumors (P = 0.01); however, intralesional resection provided adequate control of Enneking stage II tumors. There were 6 (12%) cases of metastasis, and 2 patients died from the progression of their disease. One patient died from the complications of the surgery. En bloc resection should be considered for Enneking stage III GCTs of the mobile spine. The choice of en bloc resection must be balanced with the inherent risks of the procedure. Intralesional resection of Enneking stage II tumors provides adequate local control. Patients should be followed for at least 5 years because local relapse can occur late.


Predicted Value of MicroRNAs, Vascular Endothelial Growth Factor, and Intermediate Monocytes in the Left Adverse Ventricular Remodeling in Revascularized ST-Segment Elevation Myocardial Infarction Patients.
Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients; nevertheless, some patients develop left ventricular adverse remodeling (LVAR) a few months after the intervention. The main objective of this study was to characterize the role of pro-inflammatory cell populations, related cytokines, and microRNAs (miRNAs) released after PPCI as reliable prognostic biomarkers for LVAR in patients with STEMI. We evaluated the level of pro-inflammatory subsets, before and after revascularization, 1 and 6 months after PPCI, using flow cytometry. We also performed a miRNA microarray in isolated peripheral blood mononuclear cells (PBMCs) and examined the levels of 27 cytokines in patients' serum of patients by multiplex ELISA. We observed that the levels of classical and intermediate monocytes increased 6 h after PPCI in patients who developed LVAR later. Multivariate regression analysis and ROC curves indicated that intermediate monocytes, after PPCI, were the best monocyte subset that correlated with LVAR. Within the 27 evaluated cytokines evaluated, we found that the increase in the level of vascular endothelial growth factor (VEGF) correlated with LVAR. Furthermore, the microarray analysis of PBMCs determined that up to 1,209 miRNAs were differentially expressed 6 h after PPCI in LVAR patients, compared with those who did not develop LVAR. Using RT-qPCR we confirmed a significant increase in miR-16, miR-21-5p, and miR-29a-3p, suggested to modulate the expression of different cytokines, 6 h post-PPCI in LVAR patients. Interestingly, we determined that the combined analysis of the levels of the intermediate monocyte subpopulation, VEGF, and miRNAs gave a better association with LVAR appearance. Similarly, combined ROC analysis provided high accurate specificity and sensibility to identify STEMI patients who will develop LVAR. Our data suggest that the combined analysis of intermediate monocytes, VEGF, and miRNAs predicts LVAR in STEMI patients.


[Predispositional and "process" factors in the pathology of cognitive activity in schizophrenia].
Psychological studies demonstrated certain changes of speech and thinking in schizophrenic patients, increasing as the morbid process develops. However these changes cannot be considered as specific schizophrenic and apparently are related to changes of more general factors, determining mental activity and particular an increase in it. The conducted studies permit to single out in the pathology of cognitive activity of schizophrenia changes which are connected both with the process and predispositional factors, the interaction of which determines its expressivity in the cognitive activity during the process of a schizophrenic defect formation.


Weaning from mechanical ventilation: current controversies.
As an acute episode of respiratory failure resolves for the patient who is receiving mechanical ventilation, the sometimes difficult task of resuming spontaneous ventilation begins. The resumption of spontaneous ventilation, commonly referred to as weaning, is often difficult for the patient with preexisting lung disease. The purpose of this article is to explore the current controversies related to weaning patients from mechanical ventilation. Patients with chronic obstructive pulmonary disease are used as examples, providing the background for understanding weaning in difficult cases. Weaning is conceptualized as a process of three phases: preweaning, weaning, and extubation. Important considerations during each phase are examined.


[A simple electronic delay line that facilitates the incomplete display of spontaneous bioelectric signals on an oscilloscope].
A simple electronic delay line is described which is appropriate to delay bioelectric events like action potentials of neurons up to 100 ms. Thus, the device allows to use untriggered potentials as trigger signals and thereafter to display the delayed events including possible prepotentials in toto on an oscilloscope. The delay line mainly consists on charge coupled devices (CCD) in which samples of potentials to be delayed are transported like in "bucket-chain". Thereby the delay time at a given number of CCD elements only depends on the frequency of a clock which drives the chain. As long as action potentials and other bioelectric events have to be delayed up to ca. 0,1 s this device may be used as an alternative to transient recorders or other apparatus which are far more expensive than the presented delay line.


A Large-Scale Clinical Benchmark of ResNet-based Deep Models for Newborn Face Recognition.
Newborn face recognition is a meaningful application for obstetrics in the hospital, as it enhances security measures against infant swapping and abduction through authentication protocols. Due to limited newborn face datasets, this topic was not thoroughly studied. We conducted a clinical trial to create a dataset that collects face images from 200 newborns within an hour after birth, namely NEWBORN200. To our best knowledge, this is the largest newborn face dataset collected in the hospital for this application. The dataset was used to evaluate the four latest ResNet-based deep models for newborn face recognition, including ArcFace, CurricularFace, MagFace, and AdaFace. The experimental results show that AdaFace has the best performance, obtaining 55.24% verification accuracy at 0.1% false accept rate in the open set while achieving 78.76% rank-1 identification accuracy in a closed set. It demonstrates the feasibility of using deep learning for newborn face recognition, also indicating the direction of improvement could be the robustness to varying postures.


Interactions among catechol-O-methyltransferase genotype, parenting, and sex predict children's internalizing symptoms and inhibitory control: Evidence for differential susceptibility.
We used sex, observed parenting quality at 18 months, and three variants of the catechol-O-methyltransferase gene (Val158Met [rs4680], intron1 [rs737865], and 3'-untranslated region [rs165599]) to predict mothers' reports of inhibitory and attentional control (assessed at 42, 54, 72, and 84 months) and internalizing symptoms (assessed at 24, 30, 42, 48, and 54 months) in a sample of 146 children (79 male). Although the pattern for all three variants was very similar, Val158Met explained more variance in both outcomes than did intron1, the 3'-untranslated region, or a haplotype that combined all three catechol-O-methyltransferase variants. In separate models, there were significant three-way interactions among each of the variants, parenting, and sex, predicting the intercepts of inhibitory control and internalizing symptoms. Results suggested that Val158Met indexes plasticity, although this effect was moderated by sex. Parenting was positively associated with inhibitory control for methionine-methionine boys and for valine-valine/valine-methionine girls, and was negatively associated with internalizing symptoms for methionine-methionine boys. Using the "regions of significance" technique, genetic differences in inhibitory control were found for children exposed to high-quality parenting, whereas genetic differences in internalizing were found for children exposed to low-quality parenting. These findings provide evidence in support of testing for differential susceptibility across multiple outcomes.


Multiple forms of acetylcholinesterase from pig brain.
1. A number of methods of solubilization of pig brain acetylcholinesterase (EC 188.8.131.52) were studied. The multiple enzymic forms of the resultant preparations were examined by polyacrylamide-gel electrophoresis. 2. Butanol extraction, Nagarase treatment and ultrasonication proved unsuitable as preparatory methods, but detergent treatment (Triton X-100, Triton X-100-KCl and lysolecithin) gave good yields. 3. Separation of soluble enzyme in three systems of polyacrylamide-gel electrophoresis were compared and the relative advantages are discussed. 4. By using a 6% (w/v) gel and continuous buffer system two forms of acetylcholinesterase were detected in Triton X-100-solubilized enzyme, but the incorporation of a sample and spacer gel and a discontinuous buffer system resolved this into four components. The forms of the soluble enzyme extracted by different methods differed in mobility. 5. With gradient polyacrylamide-gel electrophoresis between two and six forms were detected, depending on the method used for extraction. The average molecular weights of the five forms most frequently found were 60000, 130000, 198000, 266000 and 350000. 6. Treatment of the Triton X-100-extracted enzyme with 2.5m-urea altered the pattern and evidence of dissociation was observed. 7. The results are discussed in the light of present theories on the molecular structure of acetylcholinesterase.


Prospective chest pain evaluation in the emergency department with use of high-sensitivity C-reactive protein (PROCEED-CRP study).
We evaluated the clinical value of a single measurement of high-sensitivity C-reactive protein (hs- CRP) in patients presenting to the emergency department with chest pain. We screened 408 consecutive patients of whom 292 comprised the final cohort for this study. Hs-CRP measured in the emergency department (ED) in patients presenting with chest pain and admitted for evaluation of acute myocardial infarction was neither sensitive nor specific in predicting acute myocardial infarction, myocardial ischemia on SPECT imaging, need for coronary revascularization, or cardiovascular or all-cause rehospitalization at 30 days. In addition, use of a specific CRP cut off >1 was not associated with an increase in all-cause rehospitalization at 30 days.


Activation of Pregnane X Receptor Sensitizes Mice to Hemorrhagic Shock-Induced Liver Injury.
Hemorrhagic shock (HS) is a life-threatening condition associated with tissue hypoperfusion and often leads to injury of multiple organs including the liver. Pregnane X receptor (PXR) is a species-specific xenobiotic receptor that regulates the expression of drug-metabolizing enzymes (DMEs) such as the cytochrome P450 (CYP) 3A. Many clinical drugs, including those often prescribed to trauma patients, are known to activate PXR and induce CYP3A. The goal of this study is to determine whether PXR plays a role in the regulation of DMEs in the setting of HS and whether activation of PXR is beneficial or detrimental to HS-induced hepatic injury. PXR transgenic, knockout, and humanized mice were subject to HS, and the liver injury was assessed histologically and biochemically. The expression and/or activity of PXR and CYP3A were manipulated genetically or pharmacologically in order to determine their effects on HS-induced liver injury. Our results showed that genetic or pharmacological activation of PXR sensitized wild-type and hPXR/CYP3A4 humanized mice to HS-induced hepatic injury, whereas knockout of PXR protected mice from HS-induced liver injury. Mechanistically, the sensitizing effect of PXR activation was accounted for by PXR-responsive induction of CYP3A and increased oxidative stress in the liver. The sensitizing effect of PXR was attenuated by ablation or pharmacological inhibition of CYP3A, treatment with the antioxidant N-acetylcysteine amide, or treatment with a PXR antagonist. Conclusion: We have uncovered a function of PXR in HS-induced hepatic injury. Our results suggest that the unavoidable use of PXR-activating drugs in trauma patients has the potential to exacerbate HS-induced hepatic injury, which can be mitigated by the coadministration of antioxidative agents, CYP3A inhibitors, or PXR antagonists.


Human cardiac progenitor cells with regenerative potential can be isolated and characterized from 3D-electro-anatomic guided endomyocardial biopsies.
In the present study, we aimed to develop a percutaneous approach and a reproducible methodology for the isolation and expansion of Cardiac Progenitor Cells (CPCs) from EndoMyocardial Biopsies (EMB) in vivo. Moreover, in an animal model of non-ischemic heart failure (HF), we would like to test whether CPCs obtained by this methodology may engraft the myocardium and differentiate. EMB were obtained using a preformed sheath and a disposable bioptome, advanced via right femoral vein in 12 healthy mini pigs, to the right ventricle. EMB were enzymatically dissociated, cells were expanded and sorted for c-kit. We used 3D-Electro-Anatomic Mapping (3D-EAM) to obtain CPCs from 32 patients affected by non-ischemic cardiomyopathy. The in vivo regenerative potential of CPCs was tested in a rodent model of drug-induced non-ischemic cardiomyopathy. c-kit positive CPCs replicative capacity was assessed in 30 patients. Telomere length averaged 7.4±0.4kbp and telomerase activity was present in all preparations (1.7×105 copies). The in situ hybridization experiments showed that injected human CPCs may acquire a neonatal myocyte phenotype given the expression of the alpha-sarcomeric actin together with the presence of the Alu probe, suggesting a beneficial impact on LV performance. The success in obtaining CPCs characterized by high regenerative potential, in vitro and in vivo, from EMB indicates that harvesting without thoracotomy in patients affected by either ischemic or non-ischemic cardiomyopathy is feasible. These initial results may potentially expand the future application of CPCs to all patients affected by HF not undergoing surgical procedures.


Clinical and Endoscopic Outcomes Through 78 Weeks of Tofacitinib Therapy for Ulcerative Colitis in a US Cohort.
Tofacitinib is an oral JAK inhibitor for the treatment of ulcerative colitis (UC). We assessed outcomes through 78 weeks of tofacitinib therapy for UC in a real-world setting. This retrospective cohort study included adults initiating tofacitinib for UC from May 1, 2018, to April 1, 2021, at a large academic center in the United States. The primary outcome was steroid-free clinical remission at 78 (+/-4) weeks (SFCR 78; simple clinical colitis activity index ≤2 with no corticosteroid use within 30 days). The secondary outcome was tofacitinib discontinuation due to nonresponse (treatment persistence). Additional outcomes were endoscopic response/remission and adverse events (AEs). Seventy-three patients initiated tofacitinib, with a median follow-up of 88 weeks. Among patients with available data, 31 of 60 (51.7%) achieved SFCR 78, 21 of 47 (44.7%) achieved endoscopic remission during follow-up, and 25 of 73 (34.2%) discontinued tofacitinib during follow-up due to nonresponse (including 11 patients who required colectomy). Nineteen AEs were reported among 15 patients during follow-up: shingles (n = 4, all without documented vaccinations), deep venous thrombosis (n = 2), elevated liver enzymes (n = 2), skin abscess (n = 2), pneumonia (n = 2), possible miscarriage (n = 2), norovirus (n = 1), COVID-19 (n = 1), lymphopenia (n = 1), Clostridioides difficile infection (n = 1), and heart block (n = 1). One patient discontinued therapy due to an AE (elevated liver enzymes), and no deaths occurred. Tofacitinib treatment was effective in achieving SFCR for the majority of patients with UC through 78 weeks. Adverse events were consistent with the known safety profile of tofacitinib, and AEs requiring discontinuation were rare. Due to limitations regarding sample size, larger studies are needed to confirm these findings.


Screening and Characterization of Potential Bacillus Starter Cultures for Fermenting Low-Salt Soybean Paste (Doenjang).
The bacterial strains were screened as potential starters for fermenting low-salt doenjang (a Korean traditional fermented soybean paste) using Korean doenjang based on proteolytic and antipathogenic activities under 6.5-7.5% NaCl conditions. Phylogenetic analysis based on 16S rRNA gene sequences showed that they all belonged to the genus Bacillus. Proteolytic and antipathogenic activities against Escherichia coli, Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, and Aspergillus flavus, as well as fibrinolytic, amylase, and cellulase activities of the 10 strains were quantitatively evaluated. Of these, strains D2-2, JJ-D34, and D12-5 were selected, based on their activities. The functional, phenotypic, and safety-related characteristics of these three strains were additionally investigated and strains D2-2 and D12-5, which lacked antibiotic resistance, were finally selected. Strains D2-2 and D12-5 produced poly-γ-glutamic acid and showed various enzyme activities, including α-glucosidase and β-glucosidase. Growth properties of strains D2-2 and D12-5 included wide temperature and pH ranges, growth in up to 16% NaCl, and weak anaerobic growth, suggesting that they facilitate low-salt doenjang fermentation. Strains D2-2 and D12-5 were not hemolytic, carried no toxin genes, and did not produce biogenic amines. These results suggest that strains D2-2 and D12-5 can serve as appropriate starter cultures for fermenting low-salt doenjang with high quality and safety.


Mechanisms of resistance to antibiotics.
Microbial resistance to antibiotics is manifested by changes in antibiotic permeability, alteration of target molecules, enzymatic degradation of the antibiotics, and efflux of antimicrobials from the cytosol. Bacteria and other microorganisms use all of these mechanisms to evade the toxic effects of antibiotics. Recent research on the molecular aspects of these mechanisms, often informed by atomic resolution structures of proteins, enzymes and nucleic acids involved in these processes, has deepened our understanding of antibiotic action and resistance and, in several cases, spurred the development of strategies to overcome resistance in vitro and in vivo.


Fractures of the dens. A multicenter study.
The treatment of fractures of the dens is often inadequate, and surgeons are divided in their opinions regarding the best surgical management of these potentially serious injuries. Because of these concerns, the Cervical Spine Research Society conducted a multicenter survey of its membership regarding the management of these fractures. Fractures of the dens can be effectively classified according to the anatomical level of the fracture, as described by Anderson and d'Alonzo. We have found that the degree of angulation and amount of displacement are also important factors. Fractures occurring at the junction of the dens with the vertebral body (Type-II fractures) were found to be the most troublesome. The initial management of these fractures with a halo device was successful in only 68 per cent; however, posterior cervical fusion was successful in 96 per cent, and that appears to be the treatment of choice. Fractures extending into the vertebral body (Type-III injuries) were found not to be as benign as has been reported. Malunion and non-union occurred in patients with this injury who were treated with an orthosis alone, and a halo device or surgery may be indicated for unstable lesions.


Frequency and spatial patterning of clonal reproduction in Louisiana iris hybrid populations.
The plant genera in which natural hybridization is most prevalent tend to be outcrossing perennials with some mechanism for clonal (i.e., asexual) reproduction. Although clonal reproduction in fertile, sexually reproducing hybrid populations could have important evolutionary consequences, little attention has been paid to quantifying this parameter in such populations. In the present study, we examined the frequency and spatial patterning of clonal reproduction in two Louisiana iris hybrid populations. Allozyme analysis of both populations revealed relatively high levels of genotypic diversity. However, a considerable amount of clonality was apparent. Nearly half of all genets (47%) in one population and more than half (61%) in the other had multiple ramets. Furthermore, both populations exhibited relatively high levels of genetic structuring, a pattern that resulted from the aggregation of clonal ramets. The occurrence of clonal reproduction in hybrid populations could not only facilitate introgression through an increase in the number of flowering ramets per genet and/or the survivorship of early generation hybrids, but might also influence the mating system of such populations. Any potential increase in the selfing rate due to cross-pollination among ramets of the same genet may, in turn, increase the likelihood of homoploid hybrid speciation.


[Conservative surgery of epidermoid cyst of the testis].
Epidermoid cyst of the testis is a rare, benign testicular tumor. It is estimated that epidermoid cyst of the testis represent less than 1% of all testicular tumors. Opinion is divided as to the best treatment for this condition. The majority opinion favours excision of the tumour and preservation of the testis, although some recommend radical inguinal orchiectomy. We present a case of a 26 years old man with an epidermoid cyst of the testis and submitted to organ preserving surgery. Organ preserving surgery with the excision or enucleation of the epidermoid cyst suffices, having not been reported relapse or metastasis after such treatment. The longest reported follow up time is 37 years. The conservative management of epidermoid cyst is an alternative with important psycho logical benefits and without jeopardizing life.


The increasing incidence of remote metastasis: a case report of metastatic hepatocellular carcinoma to the rectosigmoid.
As the fifth most common malignancy worldwide, survival rates of hepatocellular carcinoma (HCC) have only slightly improved over the years due to early-stage detection. HCC is well known to metastasize to the lung, lymph nodes, and musculoskeletal regions; however, only 0.5% to 6% of HCCs metastasize to the gastrointestinal tract. In the case described here, a CT scan and subsequent colonoscopy of a 51-year-old Asian male with a history of hepatitis B and HCC revealed a mass lesion of metastatic HCC 12 cm from the anal verge. Because metastatic HCC to the lower gastrointestinal tract has only recently been reported, it is speculated that the prolonged survival of patients is also increasing the incidence of extrahepatic metastasis, giving the disease greater opportunity to spread to more distant regions of the body. This case may be the farthest metastasis within the gastrointestinal tract to date.


An Examination of the Roles of Mental Health Literacy, Treatment-Seeking Stigma, and Perceived Need for Care in Female Veterans' Service Use.
Little is known about the role of mental health literacy in military veterans' treatment-seeking stigma and service use, or the impact of these factors on perceived need for mental health care. In addition, most research has focused on mixed-gender samples. This study examined the relationships among mental health literacy, treatment seeking stigma, perceived need for mental health care, and service use in a national, longitudinal study of female veterans. A sample of 171 female veterans were drawn from a larger three-wave prospective national survey conducted between 2014 and 2017. Path analyses revealed that treatment seeking stigma had a direct negative effect on service use and an indirect effect that was mediated by perceived need for care, such that higher treatment seeking stigma was associated with lower perceived need for mental health care. Mental health literacy had an indirect effect on service use via its inverse association with treatment-seeking stigma. In contrast, mental health literacy was not associated with perceived need. Mental health literacy, treatment-seeking stigma, and perceived need for care affect female veterans' service use in unique ways. Further longitudinal research is needed to better understand these pathways in diverse samples.


Characterization of the atypical Ppz/Hal3 phosphatase system from the pathogenic fungus Cryptococcus neoformans.
Ppz Ser/Thr protein phosphatases (PPases) are found only in fungi and have been proposed as potential antifungal targets. In Saccharomyces cerevisiae Ppz1 (ScPpz1) is involved in regulation of monovalent cation homeostasis. ScPpz1 is inhibited by two regulatory proteins, Hal3 and Vhs3, which have moonlighting properties, contributing to the formation of an unusual heterotrimeric PPC decarboxylase (PPCDC) complex crucial for CoA biosynthesis. Here we report the functional characterization of CnPpz1 (CNAG_03673) and two possible Hal3-like proteins, CnHal3a (CNAG_00909) and CnHal3b (CNAG_07348) from the pathogenic fungus Cryptococcus neoformans. Deletion of CnPpz1 or CnHal3b led to phenotypes unrelated to those observed in the equivalent S. cerevisiae mutants, and the CnHal3b-deficient strain was less virulent. CnPpz1 is a functional PPase and partially replaced endogenous ScPpz1. Both CnHal3a and CnHal3b interact with ScPpz1 and CnPpz1 in vitro but do not inhibit their phosphatase activity. Consistently, when expressed in S. cerevisiae, they poorly reproduced the Ppz1-regulatory properties of ScHal3. In contrast, both proteins were functional monogenic PPCDCs. The CnHal3b isoform was crystallized and, for the first time, the 3D-structure of a fungal PPCDC elucidated. Therefore, our work provides the foundations for understanding the regulation and functional role of the Ppz1-Hal3 system in this important pathogenic fungus.


The structural basis of promiscuity in small multidrug resistance transporters.
By providing broad resistance to environmental biocides, transporters from the small multidrug resistance (SMR) family drive the spread of multidrug resistance cassettes among bacterial populations. A fundamental understanding of substrate selectivity by SMR transporters is needed to identify the types of selective pressures that contribute to this process. Using solid-supported membrane electrophysiology, we find that promiscuous transport of hydrophobic substituted cations is a general feature of SMR transporters. To understand the molecular basis for promiscuity, we solved X-ray crystal structures of a SMR transporter Gdx-Clo in complex with substrates to a maximum resolution of 2.3 Å. These structures confirm the family's extremely rare dual topology architecture and reveal a cleft between two helices that provides accommodation in the membrane for the hydrophobic substituents of transported drug-like cations.


Fluctuating fitness shapes the clone-size distribution of immune repertoires.
The adaptive immune system relies on the diversity of receptors expressed on the surface of B- and T cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types (B cells, T cells, naive, memory) is governed by a variety of antigenic and environmental signals, yet the observed clone sizes follow a universal power-law distribution. Guided by this reproducibility we propose effective models of somatic evolution where cell fate depends on an effective fitness. This fitness is determined by growth factors acting either on clones of cells with the same receptor responding to specific antigens, or directly on single cells with no regard for clones. We identify fluctuations in the fitness acting specifically on clones as the essential ingredient leading to the observed distributions. Combining our models with experiments, we characterize the scale of fluctuations in antigenic environments and we provide tools to identify the relevant growth signals in different tissues and organisms. Our results generalize to any evolving population in a fluctuating environment.


T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation.
An mAb MRC OX-22, reactive with the high molecular weight forms of the rat leukocyte-common antigen, has revealed a heterogeneity among CD4+ T cells in this species. Approximately two-thirds are CD4+, OX-22+, and one-third are CD4+, OX-22-. This phenotypic heterogeneity was found to be associated with a functional one. CD4+, OX-22+ cells proliferated well in mixed leukocyte culture, responded to the T cell mitogen Con A, and produced IL-2 on activation. In contrast, the CD4+, OX-22- cells performed poorly in these assays, but unlike CD4+, OX-22+ cells, did provide effective help for B cells. By sampling supernatants from cultures containing primed B cells and either of the two CD4+ T cell subsets, it was shown that, when specific antigen was included in the cultures, those containing the OX-22- subset of CD4+ cells produced high levels of antibody and some IL-2, whereas those containing the OX-22+ cells produced neither. In contrast, when specific antigen was replaced by Con A, the B cell cultures supplemented with CD4+, OX-22+ cells synthesized much higher levels of IL-2 than those containing CD4+, OX-22- cells, but only the latter cultures produced detectable levels of antibody. The data show that inducer/helper T cells comprise two functional subsets: one that, on appropriate stimulation, synthesizes high levels of IL-2, and may therefore be presumed to play an important role in cell-mediated immunity, and another that plays an essential role in humoral responses to soluble antigens. The significance of this functional heterogeneity, with regard to the possible independent regulation of cellular and humoral responses, is briefly considered.


Inhibition of the SEC61 translocon by mycolactone induces a protective autophagic response controlled by EIF2S1-dependent translation that does not require ULK1 activity.
The Mycobacterium ulcerans exotoxin, mycolactone, is responsible for the immunosuppression and tissue necrosis that characterizes Buruli ulcer. Mycolactone inhibits SEC61-dependent co-translational translocation of proteins into the endoplasmic reticulum and the resultant cytosolic translation triggers degradation of mislocalized proteins by the ubiquitin-proteasome system. Inhibition of SEC61 by mycolactone also activates multiple EIF2S1/eIF2α kinases in the integrated stress response (ISR). Here we show mycolactone increased canonical markers of selective macroautophagy/autophagy LC3B-II, ubiquitin and SQSTM1/p62 in diverse disease-relevant primary cells and cell lines. Increased formation of puncta positive for the early autophagy markers WIPI2, RB1CC1/FIP200 and ATG16L1 indicates increased initiation of autophagy. The mycolactone response was SEC61A1-dependent and involved a pathway that required RB1CC1 but not ULK. Deletion of Sqstm1 reduced cell survival in the presence of mycolactone, suggesting this response protects against the increased cytosolic protein burden caused by the toxin. However, reconstitution of baseline SQSTM1 expression in cells lacking all autophagy receptor proteins could not rescue viability. Translational regulation by EIF2S1 in the ISR plays a key role in the autophagic response to mycolactone. Mycolactone-dependent induction of SQSTM1 was reduced in eif2ak3-/-/perk-/- cells while the p-EIF2S1 antagonist ISRIB reversed the upregulation of SQSTM1 and reduced RB1CC1, WIPI2 and LC3B puncta formation. Increased SQSTM1 staining could be seen in Buruli ulcer patient skin biopsy samples, reinforcing genetic data that suggests autophagy is relevant to disease pathology. Since selective autophagy and the ISR are both implicated in neurodegeneration, cancer and inflammation, the pathway uncovered here may have a broad relevance to human disease.Abbreviations: ATF4: activating transcription factor 4; ATG: autophagy related; BAF: bafilomycin A1; ATG16L1: autophagy related 16 like 1; BU: Buruli ulcer; CQ: chloroquine; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; CALCOCO2: calcium binding and coiled-coil domain 2; DMSO: dimethyl sulfoxide; EIF2S1: eukaryotic translation initiation factor 2 subunit alpha; ER: endoplasmic reticulum; GFP: green fluorescent protein; HDMEC: human dermal microvascular endothelial cells; HFFF: human fetal foreskin fibroblasts; ISR: integrated stress response; ISRIB: integrated stress response inhibitor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; Myco: mycolactone; NBR1: NBR1 autophagy cargo receptor; NFE2L2: nuclear factor, erythroid 2 like 2; OPTN: optineurin; PFA: paraformaldehyde; PtdIns3P: phosphatidylinositol-3-phosphate; RB1CC1: RB1-inducible coiled coil 1; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; ULK: unc-51 like autophagy activating kinase; UPS: ubiquitin-proteasome system; WIPI: WD repeat domain, phosphoinositide interacting; WT: wild type.


The effectiveness of a verbal opt-out system for human immunodeficiency virus screening during pregnancy.
We sought to evaluate the use of human immunodeficiency virus (HIV) screening during pregnancy in a health care system using the verbal opt-out method, in which HIV screening was recommended during all pregnancies and women were given an opportunity to refuse testing. This was a retrospective cohort study of pregnancies resulting in delivery from 1998 through 2001 at Denver Health Medical Center, an urban public hospital. The main outcome measure was the proportion of documented HIV screening within 9 months before the delivery date. Of 12,221 pregnancies resulting in delivery, HIV screening was completed in 12,000 (98.2%, 95% confidence interval 97.9-98.4%). Of the 221 women not screened for HIV, only 24 (10.9% of those not screened, 0.2% of all women in the study) were documented as refusing HIV testing. Patients not screened for HIV presented late in pregnancy, a median of 1 day before delivery, compared with a median of 176 days for those who were screened (P <.001). A verbal opt-out system was very effective in promoting HIV screening during pregnancy. Late presentation in pregnancy was associated with not having HIV screening performed.


The detection of depression by patient self-report in women with gynecologic cancer.
We examined the utility of patient self-report forms in identifying those gynecologic oncology patients who would be diagnosed by an experienced consultation-liaison psychiatrist as suffering from major depression. Sixty-five women with gynecologic tumors were evaluated by a consultation-liaison psychiatrist, using standardized (DSM-III) criteria. Each patient also completed a Carroll Rating Scale for Depression (CRS). The CRS demonstrated sensitivity and specificity of 87 percent and 58 percent, respectively. Used as a screening instrument to rule out depression, the CRS yielded a negative predictive value of 94 percent. We identified a priori forty items from the CRS which should not be influenced by the non-psychiatric biologic effects of gynecologic tumors, and compared the performance of this non-cancer related symptoms subscale (NCSG) to that of the CRS. The NCSG did not significantly outperform the CRS; its sensitivity and specificity were 87 percent and 62 percent, respectively. Because our study population was relatively homogeneous (i.e., non-ovarian gynecologic oncology patients without severe debilitation who were not receiving chemotherapy, radiation therapy, or other invasive procedures), the findings should not be generalized to other oncologic populations at this time. Our results suggest that patient self-report forms can be effective screening devices for identifying those non-ovarian, gynecologic oncology patients who should then be carefully evaluated for coexisting clinical depression.


Pyridoxine therapy on Nigerian children with infantile spasms.
Nine Nigerian children, with infantile spasms, 4 boys and 5 girls age 2.5-15 months, were treated with high doses of vitamin B6. Unlike results from some European and Japanese centres, our results have not been encouraging. Possible reasons for this poor response are suggested.


Plasma neurofilament light as a potential biomarker for cognitive decline in a longitudinal study of middle-aged urban adults.
Plasma neurofilament light (NfL) is a marker for neurodegenerative diseases. Few studies have examined the association of NfL with middle-aged changes in cognitive performance, and no studies have examined differential NfL effects by race. Using data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 625, Agev1: 30-66 y, 41.6% male, 56.3% African American, 27.8% below poverty), we investigated the associations of initial NfL levels and annualized change with cognitive performance over time in global mental status, verbal and visual memory, fluency, attention, and executive function. We used ordinary least squares and mixed-effects regressions stratified by race, while exploring differential associations by age group, sex, and poverty status. Over a mean follow-up of 4.3 years, we found initial NfL level was associated with a faster decline on normalized mental status scores in Whites only and in those >50 years old. Annualized increase in NfL was associated with a greater decline in verbal fluency in men. In other exploratory analyses, annualized increase in NfL was associated with a slower decline in verbal memory among individuals living above poverty; in the older group (>50 years), first-visit NfL was linked with better performance at baseline in global mental status and verbal memory. In summary, first-visit NfL was primarily associated with the global mental status decline among Whites, while exhibiting inconsistent relationships in some exploratory analyses. Plasma NfL levels can be detected and quantified in non-demented middle-aged adults and changes can be analyzed over time. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.


A retrospective comparison of programmed intermittent epidural bolus with continuous epidural infusion for maintenance of labor analgesia.
To assess whether maintenance of labor epidural analgesia using programmed intermittent epidural bolus (PIEB) is associated with reduced local anesthetic (LA) consumption, patient-controlled epidural analgesia (PCEA) use, and rescue analgesia requirements compared to continuous epidural infusion (CEI). This is a retrospective study at an academic university medical center. Women receiving epidural labor analgesia from March to July of 2015 were identified and categorized into three groups: 1) CEI 5 mL/hr, 2) PIEB 5 mL/60 minutes, 3) PIEB 3 mL/30 minutes. The LA consisted of bupivacaine 0.125 mg/mL and fentanyl 2 μg/mL. All patients had similar PCEA settings. Data were collected on pattern of LA usage, obstetric outcomes and Bromage scores. The primary endpoint was total volume of LA consumed per hour. Secondary outcomes included need for clinician boluses, pattern of PCEA use, degree of motor blockade and delivery mode. We included 528 patients (262 had CEI, 162 had PIEB 5 mL/60 minutes, and 104 had PIEB 3 mL/30 minutes). Median LA consumed was 10.3, 9.5, and 9.7 mL/hr, respectively (p = 0.10). There were no differences in PCEA attempts or rescue clinician boluses, but PCEA volume (p = 0.03) and ratio of PCEA attempts/given (p < 0.01) were significantly different among the groups. Patients receiving PIEB 3 mL/30 minutes used lower PCEA volume than patients receiving CEI (p = 0.04). Patients with PIEB 5 mL/60 minutes and PIEB 3 mL/30 minutes had a higher ratio of PCEA attempts/given than CEI patients (p = 0.01 and p < 0.01, respectively). There were no differences in Bromage scores (p = 0.14) or delivery mode (p = 0.55) among the groups. The epidural maintenance regimen used (CEI vs. PIEB) was not associated with differences in LA consumption, motor blockade or delivery mode. Main limitations of the study include its single center retrospective design and the fact that patients were not randomized to treatment groups.


A peptide derived from acetylcholinesterase induces neuronal cell death: characterisation of possible mechanisms.
Acetylcholinesterase (AChE) exhibits functions unrelated to the catalysis of acetylcholine (ACh) in particular during development. Although the underlying mechanism(s) is presently unknown, a candidate peptide fragment (AChE-peptide) has recently been identified, and been shown to induce a continuum of apoptotic and necrotic neuronal cell death in rat hippocampal organotypic cultures. The aim of this study was to trace the cell death pathway initiated by AChE-peptide. Using specific antagonists, it was possible to track a series of cellular events following application of 1 nM AChE-peptide: NMDA receptor activation, opening of the L-type voltage gated calcium channel, activation of calcium/calmodulin kinase II, generation of reactive oxygen species and caspase activation. Pharmacological interception at any stage of this cascade blocked the effect of 1 nM AChE-peptide on neurite retraction. Lactate dehydrogenase (LDH) release, a marker for cell lysis, was unaffected by 1 nM AChE-peptide. In contrast, cell death induced by 1 mM AChE-peptide, monitored as neurite retraction and increased LDH efflux, was not offset by any drug treatment. These data suggest that nanomolar concentrations of AChE-peptide exhibit pathophysiological activity via an apoptotic pathway that could play an important role in neuronal development and neurodegeneration.


Cognitive Attributes, Attention, and Self-Efficacy of Adequate and Inadequate Responders in a Fourth Grade Reading Intervention.
We examined cognitive attributes, attention, and self-efficacy of fourth grade struggling readers who were identified as adequate responders (n = 27), inadequate responders with comprehension only deficits (n = 46), and inadequate responders with comprehension and word reading deficits (n = 52) after receiving a multicomponent reading intervention. We also included typical readers (n = 40). These four groups were compared on measures of nonverbal reasoning, working memory, verbal knowledge, listening comprehension, phonological awareness, and rapid naming as well as on teacher ratings of attention problems and self-reported self-efficacy. The two inadequate responder groups demonstrated difficulties primarily with verbal knowledge and listening comprehension compared to typical readers and adequate responders. Phonological awareness and rapid naming differentiated the two inadequate responder groups. In addition, both inadequate responder groups showed more attention problems and low self-efficacy compared to typical readers.


Laproscopic versus open appendectomy: a comparative study.
To compare the results of open with laparoscopic appendectomy in terms of postoperative pain, rate of wound infection and hospital stay. This quasi-experimental study was conducted in Deprtment of Surgery, Ziauddin University Hospital, Karachi, over a period of six months. Patients undergoing surgery for acute appendicitis were randomly assigned into one of the two groups (A or B) after obtaining written and informed consent. In Group-A patients underwent open appendectomy and in Group B laparoscopic appendectomy was performed. Post operatively pain chart and wound infection was recorded and, at the time of discharge, number of days in hospital was calculated. Sixty patients (38 male, 22 female), with clinical diagnosis of acute appendicitis based on Alvarado score of six and above, were included in the study. They were randomized into 2 groups of A and B with 30 patients in each group. Group-A comprised open appendectomy procedure and Group-B comprised laparoscopic appendectomy. Mean comparison of postoperative pain by visual analogue scale, was significantly low in Group B, compared with Group A, on day 0, 1 and 2. Number of days in Hospital was 4.1 +/- 0.8 days in Group A and 1.5 +/- 0.06 days in Group B. None of the patients in Group B, while 8 (26.67%) patients in-Group A, developed postoperative wound infection at 1 week follow up. Laparoscopic appendectomy is safe and effective. Wound infection and postoperative pain is significantly lower after this mode of surgery


Historical contingency and the gradual evolution of metabolic properties in central carbon and genome-scale metabolisms.
A metabolism can evolve through changes in its biochemical reactions that are caused by processes such as horizontal gene transfer and gene deletion. While such changes need to preserve an organism's viability in its environment, they can modify other important properties, such as a metabolism's maximal biomass synthesis rate and its robustness to genetic and environmental change. Whether such properties can be modulated in evolution depends on whether all or most viable metabolisms - those that can synthesize all essential biomass precursors - are connected in a space of all possible metabolisms. Connectedness means that any two viable metabolisms can be converted into one another through a sequence of single reaction changes that leave viability intact. If the set of viable metabolisms is disconnected and highly fragmented, then historical contingency becomes important and restricts the alteration of metabolic properties, as well as the number of novel metabolic phenotypes accessible in evolution. We here computationally explore two vast spaces of possible metabolisms to ask whether viable metabolisms are connected. We find that for all but the simplest metabolisms, most viable metabolisms can be transformed into one another by single viability-preserving reaction changes. Where this is not the case, alternative essential metabolic pathways consisting of multiple reactions are responsible, but such pathways are not common. Metabolism is thus highly evolvable, in the sense that its properties could be fine-tuned by successively altering individual reactions. Historical contingency does not strongly restrict the origin of novel metabolic phenotypes.


Levels of organochlorine pesticides in the blood of people living in areas of intensive pesticide use in Sudan.
Ninety-six human blood samples were collected from six locations that represent areas of intensive pesticide use in Sudan, which included irrigated cotton schemes (Wad Medani, Hasaheesa, Elmanagil, and Elfaw) and sugarcane schemes (Kenana and Gunaid). Blood samples were analyzed for organochlorine pesticide residues by gas liquid chromatography (GLC) equipped with an electron capture detector (ECD). Residues of p,p'-dichlorodiphenyldichloroethylene (DDE), heptachlor epoxide, γ-HCH, and dieldrin were detected in blood from all locations surveyed. Aldrin was not detected in any of the samples analyzed, probably due to its conversion to dieldrin. The levels of total organochlorine burden detected were higher in the blood from people in the irrigated cotton schemes (mean 261 ng ml(-1), range 38-641 ng ml(-1)) than in the blood of people from the irrigated sugarcane schemes (mean 204 ng ml(-1), range 59-365 ng ml(-1)). The highest levels of heptachlor epoxide (170 ng ml(-1)) and γ-HCH (92 ng ml(-1)) were observed in blood samples from Hasaheesa, while the highest levels of DDE (618 ng ml(-1)) and dieldrin (82 ng ml(-1)) were observed in blood samples from Wad Medani and Kenana, respectively. The organochlorine levels in blood samples seemed to decrease with increasing distance from the old irrigated cotton schemes (Wad Medani, Hasaheesa, and Elmanagil) where the heavy application of these pesticides took place historically.


Comparison of three PCR techniques for detecting cytomegalovirus (CMV) DNA in serum, detection of early antigen fluorescent foci and culture for the diagnosis of CMV infection.
Three PCR assays were developed for detection of cytomegalovirus (CMV) DNA in serum and were evaluated with samples from organ transplant recipients. The Qiamp Blood Kit was efficient for extraction of DNA from sera. Single-round PCR of a 293-bp region of CMV DNA was sensitive and highly specific for CMV targets and was more sensitive than detection of early antigen fluorescent foci (DEAFF) testing or isolation of CMV from buffy coat by cell culture. The results of a significant proportion of buffy coat samples were not interpretable because of toxicity in conventional culture or DEAFF tests. A non-competitive quantitative PCR test and semi-quantitative PCR test for the detection of CMV DNA in serum yielded comparable results for samples taken serially from three bone marrow transplant recipients. Single-round PCR was superior to conventional techniques for the diagnosis of CMV infection, was simple to perform and was completed rapidly. The semi-quantitative technique has added advantages where quantification is important.


Optimal finite-range atomic basis sets for liquid water and ice.
Finite-range numerical atomic orbitals are the basis functions of choice for several first principles methods, due to their flexibility and scalability. Generating and testing such basis sets, however, remains a significant challenge for the end user. We discuss these issues and present a new scheme for generating improved polarization orbitals of finite range. We then develop a series of high-accuracy basis sets for the water molecule, and report on their performance in describing the monomer and dimer, two phases of ice, and liquid water at ambient and high density. The tests are performed by comparison with plane-wave calculations, and show the atomic orbital basis sets to exhibit an excellent level of transferability and consistency. The highest-order bases (quadruple-ζ) are shown to give accuracies comparable to a plane-wave kinetic energy cutoff of at least ~1000 eV for quantities such as energy differences and ionic forces, as well as achieving significantly greater accuracies for total energies and absolute pressures.


Associations Among Quadriceps Strength and Rate of Torque Development 6 Weeks Post Anterior Cruciate Ligament Reconstruction and Future Hop and Vertical Jump Performance: A Prospective Cohort Study.
Study Design Prospective cohort. Background Quadriceps strength is associated with hop distance and jump height in persons who have undergone anterior cruciate ligament (ACL) reconstruction. However, it is unknown whether the ability to rapidly generate quadriceps torque in the early phase of recovery is associated with future hopping and jumping performance in this population. Objective To evaluate the prospective associations among quadriceps strength and rate of torque development (RTD) and single-leg hop for distance, vertical jump height, vertical ground reaction force (vGRF), and vertical force loading rate during a landing task in persons who have undergone ACL reconstruction. Methods Seventy patients with unilateral ACL reconstruction participated. At 6 weeks post ACL reconstruction, isometric quadriceps strength and RTD were measured using a dynamometer. At 6 months following ACL reconstruction, patients performed the single-leg hop for distance test. Patients also performed the single-leg vertical jump test on a force plate that measured maximum jump height, vGRF, and average loading rate during landing. Results Both quadriceps strength and RTD at 6 weeks post ACL reconstruction were associated with all hopping and jumping measures at 6 months post ACL reconstruction (P≤.04). Single-leg hop distance was associated more closely with quadriceps strength than with quadriceps RTD (P = .05), and vertical jump height and vGRF measures were associated more closely with quadriceps RTD than with quadriceps strength (P = .05 and P<.01, respectively). Both quadriceps measures were associated with loading rate. Conclusion Quadriceps strength and RTD are complementary but distinct predictors of future hopping and jumping performance in persons who have undergone ACL reconstruction. These findings may contribute to improved rehabilitation of patients who are at risk for poor jumping/hopping performance and abnormal knee loading. J Orthop Sports Phys Ther 2017;47(11):845-852. Epub 13 Oct 2017. doi:10.2519/jospt.2017.7133.


[Indications for, and the significance of, the tuberculin test in the Netherlands].
The almost 100-year-old tuberculin skin test still is the gold standard for diagnosing Mycobacterium tuberculosis infection. The sensitivity of this test with the usual cut-off values is high, but may be decreased with impaired cellular immunity and at older age. The specificity is primarily determined by cross-reactivity to atypical mycobacterial infections and vaccination with Bacillus Calmette-Guérin (BCG). Positivity of the skin test after BCG vaccination decreases with time after vaccination and depends on the age when vaccinated. The tuberculin reaction can be boosted by repeated tuberculin skin tests over a short time period, whereby the anamnestic immune response is stimulated. This boosting phenomenon occurs mostly with atypical mycobacterial infections, after BCG vaccination and at older age. Interpretation of the tuberculin skin test depends on the indication for the test, the expected risk of latent tuberculosis infection, higher prevalence of 'old' tuberculosis in elderly Dutch people and immigrants, BCG vaccination status and, if a baseline value is available, the boosting phenomenon. Its role in the diagnosis of tuberculosis is limited.


Mechanical studies of single ribosome/mRNA complexes.
Methodology was developed for specifically anchoring Escherichia coli 70S ribosomes onto a chemically modified, cysteine-reactive glass surface. Immobilized ribosomes maintain the capability of binding a polyuridylic acid (poly(U)) template, enabling investigation of mechanical properties of individual ribosome-poly(U) complexes using laser tweezers. Streptavidin-coated polystyrene microspheres bound specifically to the biotinylated 3' end of long (up to 10,000 bases) poly(U) strands. A novel optical method was built to control the position of the laser trap along the microscope optical axis at 2 nm resolution, facilitating measurement of the force-extension relationship for poly(U). Some immobilized ribosome-poly(U) complexes supported 100 pN of force applied at the 3' end of the mRNA. Binding of N-acetylated Phe-tRNA(Phe), an analog of the initiator fMet-tRNA(Met), enhanced the population of complexes that could withstand high forces. The persistence length of poly(U) RNA homopolymer, modeled as a worm-like chain, was found to be 0.79 +/- 0.05 nm and the backbone elasticity was 900 +/- 140 pN, similar to values for single-stranded DNA.


A robust and accurate method for calculating the fractal signature of texture in macroradiographs of osteoarthritic knees.
In osteoarthritis of the knee, horizontal trabeculae in the tibia thicken, leading to the appearance of horizontal striations on radiographs. Any attempt to understand and monitor the disease process must examine these changes. We have previously described a method of analysing the texture in these images that uses the mathematical morphology operations of dilation and erosion to calculate how image fractal dimension varies with resolution. This variation with resolution is the fractal signature. Calculation of fractal dimension should be independent of linear transformations in image values, and it is shown that careful choice of morphological structuring element is required for this. In this paper we describe the dependence of our method of calculating the fractal signature on image acquisition and digitization parameters. Errors due to variations in pixel size, X-ray exposure, and patient repositioning are small compared to the changes seen in the signature due to osteoarthritic change. Using pairs of orthogonal structuring elements, one tuned to calculate the signature due to horizontal image structure and the other for vertical image structure, texture directionality is examined. The difference between the two resulting signatures in individual knees is shown to be a measure of the change in texture seen in osteoarthritis.


Homodyne dynamic light scattering in supramolecular polymer solutions: anomalous oscillations in intensity correlation function.
Dilute solutions of electronically active molecules capable of irradiation-driven supramolecular self-assembly are studied by dynamic light scattering. We detect unusual well-defined oscillations in the long time range of the homodyne intensity correlation function for all solutions that were irradiated with white light prior to the measurements. The oscillation effect is attributed to the local laser-induced heating of the samples due to strongly enhanced absorption manifested by the supramolecular filaments. It is found that the oscillation frequency depends on the irradiation time, solution concentration, and the incident laser power, but is independent of the scattering angle. These observations are explained with a semi-quantitative theory relating the oscillation effect to thermo-gravitational convection flows generated by laser beam. The results suggest that the presence of such homodyne oscillations could be a sensitive probe for aggregation in many complex systems.


A plant-specific transcription factor IIB-related protein, pBRP2, is involved in endosperm growth control.
General transcription factor IIB (TFIIB) and TFIIB-related factor (BRF), are conserved RNA polymerase II/III (RNAPII/III) selectivity factors that are involved in polymerase recruitment and transcription initiation in eukaryotes. Recent findings have shown that plants have evolved a third type of B-factor, plant-specific TFIIB-related protein 1 (pBRP1), which seems to be involved in RNAPI transcription. Here, we extend the repertoire of B-factors in plants by reporting the characterization of a novel TFIIB-related protein, plant-specific TFIIB-related protein 2 (pBRP2), which is found to date only in the Brassicacea family. Unlike other B-factors that are ubiquitously expressed, PBRP2 expression is restricted to reproductive organs and seeds as shown by RT-PCR, immunofluorescence labelling and GUS staining experiments. Interestingly, pbrp2 loss-of-function specifically affects the development of the syncytial endosperm, with both parental contributions required for wild-type development. pBRP2, is the first B-factor to exhibit cell-specific expression and regulation in eukaryotes, and might play a role in enforcing bi-parental reproduction in angiosperms.


Genome-wide analysis of histone modifications in human endometrial stromal cells.
Dramatic changes of gene expressions occur in human endometrial stromal cells (ESCs) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by histone modifications. Here we investigated genome-wide changes in histone modifications associated with decidualization in human ESCs using chromatin immunoprecipitation combined with next-generation sequencing. ESCs were incubated with estradiol and medroxyprogesterone acetate for 14 days to induce decidualization. The chromatin immunoprecipitation-sequence data showed that induction of decidualization increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in only a few regions. Most of the H3K27ac-increased regions (80%) and half of the H3K4me3-increased regions were located in the distal promoter regions (more than 3 kb upstream or downstream of the transcription start site). RNA sequence showed that induction of decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Induction of decidualization increased the mRNA levels of these genes more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3-increased regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with the insulin signaling, which may be involved in glucose uptake that is necessary for ESCs to undergo decidualization. These results show that histone modification statuses on a genome-wide basis change in human ESCs during decidualization. The main changes of histone modifications are increases of H3K27ac and H3K4me3 in both the proximal and distal promoter regions, which are involved in the up-regulation of gene expression that occurs during decidualization.


[Interleukin-6 levels changes in cervicovaginal exudates in labor evolution].
To evaluate the secretion of interleukin 6 (IL-6) in cervicovaginal fluid in a pseudocohort that emulates the evolution of the labor. Samples of cervicovaginal fluid of patients with 20 to 40 weeks of gestation were taken, patients were classified in 5 strata of the development of the labor. Each stratum reflects the progressive activation of the uterine activity and the cervical changes. To each sample was made determination of IL-6 by means of the system Multiplex. The samples of patient with infection data were eliminated. 173 samples were included distributed in each one of the five strata. Basal secretion exists of IL-6 to the cervicovaginal fluid along the gestation, that doesn't modify until the active labor appears. Only when the uterine activity is manifested in form to regulate and effective, very significant increase is documented in the concentration of the IL-6 in the cervicovaginal fluid. The IL-6 it is a proinflammatory cytokine that increases in a specific way in the moment in that the effective uterine activity begins, thus, it is an excellent candidate to be evaluated as marker presage of the event of normal labor and preterm.


Differential effect of ATP binding cassette transporter A1 R219K and cholesteryl ester transfer protein TaqIB genotypes on HDL-C levels in overweight/obese and non-obese Chinese subjects.
ATP-binding cassette transporter A1 (ABCA1) and cholesteryl ester transfer protein (CETP) are involved in the HDL metabolism and play a key role in reverse cholesterol transport. The study aim was mainly to examine the possible association of the ABCA1 and CETP polymorphisms with overweight/obesity in a South-West Chinese population. Three hundred and thirty-eight Han Chinese (206 overweight/obese and 132 normal control subjects) in Chengdu area were studied using the PCR-RFLP analysis. The genotype and allele frequencies of the ABCA1 R219K, CETP Taq IB and -629C > A polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to those of the control subjects. However, on analysis of the HDL-C levels, cases showed statistically higher levels among those carrying the ABCA 1 KK genotype compared to RR genotype carriers, and controls having the CETP B2B2 genotype had a marginally significantly higher serum HDL-C concentration than those of the B1B1 genotype. In addition, the combined genotype effect of the ABCA1 R219K and the CETP Taq IB polymorphisms on HDL-C levels was evident in the control subjects: the carriers of the KK/B2B2 genotype showed the highest levels of HDL-C (2.23 +/- 0.91 mmol/L), whereas those of the RR/B1B1 genotype showed the lowest (1.32 +/- 0.33 mmol/L). There were significant differences of the HDL-C levels between subjects with genotype KK/B2B2 and those with each of the other genotype combinations (all P < 0.05). Polymorphisms of theABCA1 and CETP genes are associated with altered plasma HDL-C concentrations.These associations on HDL-C levels are modified by BMI in a Chinese population of the Chengdu area.


Neuronal expression of a functional receptor for the C5a complement activation fragment.
The present studies were undertaken to determine whether neuronal subsets in normal brains constitutively express functionally competent C5a receptors. In situ hybridization studies coupled with immunohistochemical approaches revealed that most neurons in the hippocampal formation, many pyramidal cortical neurons, and cerebellar Purkinje neurons in normal human and murine brains constitutively express C5a receptors. Neuronal C5a receptors bound C5a-coated fluorescent microspheres, and primary rodent hippocampal neurons responded to C5a with increased calcium fluxes via a pertussis-sensitive, presumably Gi-coupled protein. Additional studies with human neuroblastoma cells conducted to address the functional role of C5a receptors revealed that C5a triggered rapid activation of protein kinase C and activation and nuclear translocation of the NF-kappa B transcription factor. In addition, C5a was found to be mitogenic for undifferentiated human neuroblastoma cells, a novel action for the C5aR. In contrast, C5a protected terminally differentiated human neuroblastoma cells from toxicity mediated by the amyloid A beta peptide. Thus, normal rodent hippocampal neurons as well as undifferentiated and differentiated human neuroblastoma cells express functional C5a receptors. These results have implications for understanding the role of neuronal C5aR receptors in normal neuronal development, neuronal homeostasis, and neuroinflammatory conditions such as Alzheimer's disease.


Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo.
In multiple sclerosis (MS), chronic active lesions, which previously could only be detected at autopsy, can now be identified on susceptibility-based magnetic resonance imaging (MRI) in vivo as non-gadolinium-enhancing lesions with paramagnetic rims. Pathologically, they feature smoldering inflammatory demyelination at the edge, remyelination failure, and axonal degeneration. To our knowledge, the prospect of long-term in vivo monitoring makes it possible for the first time to determine their contribution to disability and value as a treatment target. To assess whether rim lesions are associated with patient disability and long-term lesion outcomes. We performed 3 studies at the National Institutes of Health Clinical Center: (1) a prospective clinical/radiological cohort of 209 patients with MS (diagnosis according to the 2010 McDonald revised MS criteria, age ≥18 years, with 7-T or 3-T susceptibility-based brain MRI results) who were enrolled from January 2012 to March 2018 (of 209, 17 patients [8%] were excluded because of uninterpretable MRI scans); (2) a radiological/pathological analysis of expanding lesions featuring rims; and (3) a retrospective longitudinal radiological study assessing long-term lesion evolution in 23 patients with MS with yearly MRI scans for 10 years or more (earliest scan, 1992). (1) Identification of chronic rim lesions on 7-T or 3-T susceptibility-based brain MRI in 192 patients with MS and the association of rim counts with clinical disability (primary analysis) and brain volume changes (exploratory analysis). (2) Pathological characterization of 10 expanding lesions from an adult with progressive MS who came to autopsy after 7 years of receiving serial in vivo MRI scans. (3) Evaluation of annual lesion volume change (primary analysis) and T1 times (exploratory analysis) in 27 rim lesions vs 27 rimless lesions. Of 209 participants, 104 (50%) were women and 32 (15%) were African American. One hundred seventeen patients (56%) had at least 1 rim lesion regardless of prior or ongoing treatment. Further, 84 patients (40%) had no rims (mean [SD] age, 47 [14] years), 66 (32%) had 1 to 3 rims (mean [SD] age, 47 [11] years), and 42 (20%) had 4 rims or more (mean [SD] age, 44 [11] years). Individuals with 4 rim lesions or more reached motor and cognitive disability at an earlier age. Normalized volumes of brain, white matter, and basal ganglia were lower in those with rim lesions. Whereas rimless lesions shrank over time (-3.6%/year), rim lesions were stable in size or expanded (2.2%/year; P < .001). Rim lesions had longer T1 times, suggesting more tissue destruction, than rimless lesions. On histopathological analysis, all 10 rim lesions that expanded in vivo had chronic active inflammation. Chronic active lesions are common, are associated with more aggressive disease, exert ongoing tissue damage, and occur even in individuals treated with effective disease-modifying therapies. These results prompt the planning of MRI-based clinical trials aimed at treating perilesional chronic inflammation in MS.


L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons.
The molecular basis of learning and memory has been the object of several recent advances, which have focused attention on calcium-regulated pathways controlling transcription. One of the molecules implicated by pharmacological, biochemical and genetic approaches is the calcium/calmodulin-regulated phosphatase, calcineurin. In lymphocytes, calcineurin responds to specific calcium signals and regulates expression of several immediate early genes by controlling the nuclear import of the NF-ATc family of transcription factors. Here we show that NF-ATc4/NF-AT3 in hippocampal neurons can rapidly translocate from cytoplasm to nucleus and activate NF-AT-dependent transcription in response to electrical activity or potassium depolarization. The calcineurin-mediated translocation is critically dependent on calcium entry through L-type voltage-gated calcium channels. GSK-3 can phosphorylate NF-ATc4, promoting its export from the nucleus and antagonizing NF-ATc4-dependent transcription. Furthermore, we show that induction of the inositol 1,4,5-trisphosphate receptor type 1 is controlled by the calcium/calcineurin/NF-ATc pathway. This provides a new perspective on the function of calcineurin in the central nervous system and indicates that NF-AT-mediated gene expression may be involved in the induction of hippocampal synaptic plasticity and memory formation.


Neonatal Escherichia coli infections in domestic mammals: transmissibility of pathogenic characteristics.
Apart from the fact that different serotypes are involved, natural and experimental Escherichia coli infection in domestic mammals closely resembles natural E. coli infection in human beings. Some of the important characteristics of E. coli strains that cause disease in domestic mammals are determined by transmissible plasmids. These include enterotoxin, haemolysin and K88 antigen in piglet enteropathogenic strains and enterotoxin and K99 antigen production in calf and lamb enteropathogenic strains; most strains that cause generalized infections in young domestic mammals, i.e. invasive strains, also produce plasmid-determined colicine V. These are all good reasons for employing young domestic mammals as the animal model for studying certain aspects of E. coli infection in human beings. Exploiting the fact that plasmids can be introduced into bacterial cells by conjugation and can be removed from them by "curing", bacterial strains were created that differed from each other, as far as could be determined, only by the presence or absence of one or more of these plasmid-determined properties. These strains, or cell-free preparations of them, were then given by mouth to piglets, calves, lambs and baby rabbits. The results showed that the K88 antigen, probably on account of its adhesive properties, permitted pig enteropathogenic strains of E. coli to proliferate in the small intestine of piglets; the K99 antigen performed a similar function in calf and lamb enteropathogenic strains. The enterotoxin produced by the proliferating organisms was then chiefly responsible for the subsequent movement of fluid from the body into the small intestine and the consequent diarrhoea. Possession of the Col V plasmid contributed significantly to the virulence of invasive strains of E. coli by enabling them to resist more successfully the defence mechanisms of the host.


Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.
There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.


Non-contrast enhanced simultaneous 3D whole-heart bright-blood pulmonary veins visualization and black-blood quantification of atrial wall thickness.
Pre-interventional assessment of atrial wall thickness (AWT) and of subject-specific variations in the anatomy of the pulmonary veins may affect the success rate of RF ablation procedures for the treatment of atrial fibrillation (AF). This study introduces a novel non-contrast enhanced 3D whole-heart sequence providing simultaneous information on the cardiac anatomy-including both the arterial and the venous system-(bright-blood volume) and AWT (black-blood volume). The proposed MT-prepared bright-blood and black-blood phase sensitive inversion recovery (PSIR) BOOST framework acquires 2 differently weighted bright-blood volumes in an interleaved fashion. The 2 data sets are then combined in a PSIR-like reconstruction to obtain a complementary black-blood volume for atrial wall visualization. Image-based navigation and non-rigid respiratory motion correction are exploited for 100% scan efficiency and predictable acquisition time. The proposed approach was evaluated in 11 healthy subjects and 4 patients with AF scheduled for RF ablation. Improved depiction of the cardiac venous system was obtained in comparison to a T2 -prepared BOOST implementation, and quantified AWT was shown to be in good agreement with previously reported measurements obtained in healthy subjects (right atrium AWT: 2.54 ± 0.87 mm, left atrium AWT: 2.51 ± 0.61 mm). Feasibility for MT-prepared BOOST acquisitions in patients with AF was demonstrated. The proposed motion-corrected MT-prepared BOOST sequence provides simultaneous non-contrast pulmonary vein depiction as well as black-blood visualization of atrial walls. The proposed sequence has a large spectrum of potential clinical applications and further validation in patients is warranted.


Chiropractic and osteopathic education at Royal Melbourne Institute of Technology. A student perspective.
To assess the attitudes of undergraduate chiropractic and osteopathic students at Royal Melbourne Institute of Technology (RMIT) in 1992 on the education they are receiving and on the effectiveness of chiropractic and osteopathic care. Cross-sectional descriptive survey. Undergraduate chiropractic and osteopathic students enrolled at RMIT School of Chiropractic and Osteopathy in 1992. This study surveyed 272 students, 196 who were chiropractic students and 76 who were osteopathic students from RMIT School of Chiropractic and Osteopathy in Melbourne, Australia. The students that responded represented 73.4% of chiropractic students and 85.4% of osteopathic students currently enrolled in their respective courses. Chiropractic and osteopathic students entered their respective courses from non-chiropractic/non-osteopathic families. More chiropractic students than osteopathic students (1.3:1.0) had their respective course as their first choice when applying for tertiary education. A majority (95.8 chiropractic students and 94.8% osteopathic students) of both groups surveyed were pleased with their choice of course. Students from both disciplines held considerable respect for each other in the care of certain conditions, but did not see the other profession's care as effective as their own. A greater percentage of osteopathic students believed there was sufficient difference between chiropractic and osteopathy to justify two separate professions (57.6% compared to 97.2%). High quality education is a major aim in our schools and colleges. For this standard to be maintained it requires continual re-evaluation and assessment. Surveys such as this should be performed regularly as a method of evaluating student attitude and how these attitudes change during the course. This would also allow administrators to determine whether they are achieving their academic intentions. An immediate follow up survey asking the same questions is suggested to ascertain whether the same attitudes exist today.


Analysis of telomere length and the relationship with neurocognitive functions in euthymic bipolar disorder: A cross-sectional pilot study.
Telomere shortening has been considered a potential biological marker related to disease susceptibility and aging in psychiatric disorders. However, the relationship between telomere length and bipolar disorder (BD-I and BD-II) is uncertain. Moreover, whether telomere shortening is an independent factor of cognitive impairment in BD patients is still inconclusive. We explore telomere length and cognitive function in patients with bipolar disorder and the relationship between them. We enrolled three groups (35 patients with euthymic BD-I, 18 with euthymic BD-II, and 38 healthy controls). Telomere length was measured by fluorescent quantitative polymerase chain reaction (q-PCR), and cognitive function was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). SPSS 24.0 was used for statistical analysis. The telomere length of euthymic patients with BD-I and BD-II was shorter than that of healthy controls (F = 8.228, P = 0.001, η2 = 0.176). Telomere length was not significantly different between BD-I and BD-II. Compared to HCs, poor performance was detected in attention and vigilance in BD-I patients (F = 3.473, P = 0.036). Working memory was positively correlated with telomere length in BD-II patients (Beta = 0.5, P = 0.041, Adjusted R2 = 0.2). The current study provided evidence of shortened telomere length in euthymic BD patients, indicating that telomere shortening might be a promising biomarker of susceptibility to bipolar disorder. The telomere length predicted the working memory in BD-II patients. Further studies are needed to clarify the role of accelerated aging on cognitive functioning in a young group of patients with BD.


Choroidal neovascularization associated with extensive macular atrophy and pseudodrusen.
To describe a case of extensive macular atrophy and pseudodrusen complicated by bilateral choroidal neovascularization (CNV). A 53-year-old woman showed extensive macular atrophy at the posterior pole associated with disciform scar in the right eye and fibrotic juxtafoveal CNV in the left eye. The patient underwent a complete ophthalmological examination including fundus autofluorescence, fluorescein angiography, and spectral-domain optical coherence tomography, showing a disciform scar at the posterior pole of the right eye and an extensive macular atrophy associated with a fibrotic juxtafoveal CNV. The patient was previously treated with four and seven intravitreal bevacizumab injections, respectively, in the right eye and in the left eye. Molecular analyses of the ABCA4 gene revealed the variant c.1268A<G. Although the natural course of extensive macular atrophy and pseudodrusen usually leads to the enlargement of the macular atrophy, extensive macular atrophy and pseudodrusen can also complicate with bilateral CNV. Intravitreal bevacizumab can help stop the CNV activity.


Multiple interactions of the 'transducer' govern its function in calpain activation by Ca2+.
Typical calpains in mammals become activated on binding of 8-12 Ca2+ ions per enzyme molecule, giving an example of integrated, manifold regulation by calcium. Besides two identified Ca2+ sites in catalytic domain II and several EF-hand motifs in domains IV and VI, an acidic loop in the centrally positioned domain III seems to harbour Ca2+. The mediator of distant Ca2+-induced structural transitions is an elongated structural element, the 'transducer'. By site-directed mutagenesis along the transducer, we have generated various forms of rat m-calpain in which critical intramolecular interactions, as judged from the X-ray structure, would be abolished or modified. The kinetic parameters of these mutant enzymes support a model featuring shrinkage of transducer as a contributor to structural changes involved in calpain activation.


An occlusal and cephalometric analysis of maxillary first and second premolar extraction effects.
The purpose of this study was to examine dimensional changes in the maxillary arch following the extractions of maxillary first or second premolars. Pre- and posttreatment records of 71 patients treated by one experienced orthodontist were randomly selected from completed premolar extraction cases. Forty-five patients involved the extraction of maxillary first premolars; of these, 15 also had extractions of mandibular first premolars and 30 had extractions of mandibular second premolars. Twenty-six patients involved the extraction of maxillary second premolars, and all of these also had extractions of mandibular second premolars. Pretreatment factors that seemed to suggest a basis for the extraction choice in this sample included incisal overjet, molar relationship, and maxillary incisor protrusion. Mean reductions with treatment in the anteroposterior arch dimension were similar within all premolar extraction groups. There was evidence of greater mean maxillary intermolar-width reduction following the extractions of maxillary second premolars than following extractions of maxillary first premolars. Greater mean maxillary incisor retraction was found in the maxillary first premolar extraction group than in the maxillary second premolar group. A wide range of individual variation in incisor and molar changes did, however, accompany treatment involving both maxillary premolar extraction sequences.


Is Annual Income a Predictor of Completion of Advance Directives (ADs) in Patients With Cancer.
Completion of advance directives (ADs) enhances the likelihood of receiving goal-concordant treatments near the end of life. Previous research on community samples have shown that completion of ADs is less common in lower socioeconomic status demographic group; there is a paucity of such research in patients with cancer. To study the effect of income and education on the completion of ADs. Patients with cancer having lower incomes and education levels would be less likely to report completing ADs. We conducted cross-sectional analyses of data provided by patients (n = 265) enrolled in the Values and Options in Cancer Care clinical trial. Patients with advanced cancer reported whether they had (1) completed a living will or (2) designated a health-care proxy. Response options for both questions were yes (scored 1), no (scored 0), and unsure (scored 0). We studied the association of lower household income (≤US$20 000) and education level (never attended college) with AD scores. Patients with lower annual incomes had lower AD scores (estimate -0.44; confidence intervals [CI]: -0.71 to -0.16, P = .001); the association between higher educational attainment (some college or more) and completion of ADs was not statistically significant (estimate 0.04, CI: -0.16 to 0.24, P = .70). Interventions to promote completion of ADs among lower income patients with serious illnesses are needed.