Prolactin induces maturation of glucose sensing mechanisms in cultured neonatal rat islets.
The effects of PRL treatment on insulin content and secretion, and 86Rb and 45Ca fluxes from neonatal rat islets maintained in culture for 7-9 days were studied. PRL treatment enhanced islet insulin content by 40% and enhanced early insulin secretion evoked by 16.7 mM glucose. Insulin release stimulated by oxotremorine-M, a muscarinic agonist, in the presence of glucose (8.3 or 16.7 mM) was unchanged by PRL treatment. However, PRL treatment potentiated phorbol 12,13-dibutyrate-stimulated insulin secretion in the presence of the above glucose concentrations. PRL treatment potentiated the reduction in 86Rb efflux induced by glucose or tolbutamide and enhanced the increase in 86Rb efflux evoked by diazoxide. PRL treatment slightly potentiated the increment in 45Ca uptake induced by high concentrations of K+, but failed to affect the increment evoked by 16.7 mM glucose. Since glucose-induced 45Ca uptake was not affected by PRL, we suggest that the enhancement in first phase insulin secretion evoked by glucose in the PRL-treated islets occurs at a step in the secretory process that may involve protein kinase-C. These data further support observations that PRL treatment increases islet sensitivity to glucose.


[A chronic problem-the chronic headache patient].
Chronic daily headache is a frequent problem which affects 3-5% of the population. Until the 2nd edition of the IHS headache classification, the diagnosis of chronic headache was synonymous with the diagnosis of chronic tension type headache. Now one has to differentiate, not only in symptomatic headache, but also between other primary headache syndromes, such as chronic migraine, hemicrania continua and acute persisting daily headache. Epidemiological studies point to a particular importance of chronic migraine and headache due to chronic analgetica use, since both types of headache are responsible for more than 60% of all cases with chronic headache. Although the mechanisms which cause chronification of headache are not well understood, the new headache classification prompts some direct therapeutical consequences: 1) the indication for drug withdrawal and 2) the indication for a migraine preventive therapy. In general, as with other chronic pain syndromes, there is increasing evidence that a multimodal therapy, consisting of patient education, behavioral therapy and pharmacological therapy, is more successful than a singular therapy.


Pancreas and liver resection in Jehovah's Witness patients: feasible and safe.
Jehovah's Witness (JW) patients undergoing liver or pancreas surgery represent a challenging ethical and medical problem, with few reports about their optimal management. To analyze the perioperative outcomes of JW patients submitted to hepatic or pancreatic resection, clinicopathologic data of JW patients who underwent surgical exploration for a hepatic or pancreatic tumor between March 1996 and July 2011 were reviewed retrospectively. Clinicopathologic data of 27 patients, 28 explorations, and 25 resections were included. Median age was 58 years (range 28 to 75 years) and 20 patients were female. Three patients were explored and deemed unresectable. Fifteen hepatic resections (9 segmentectomy or bi/trisegmentectomy, 6 hemi-hepatectomy or extended hepatectomy) and 10 pancreatic resections (6 pancreaticoduodenectomy, 4 distal pancreatectomy/splenectomy) were reviewed; additional organs were resected in 5 patients (2 gastrectomy, 1 colectomy, 1 nephrectomy, 1 adrenalectomy, 1 salpingoophorectomy). Median estimated blood loss for the hepatectomies was 400 mL (range 100 to 1,500 mL) and for the pancreatectomies was 400 mL (range 250 to 1,800 mL). Six patients received preoperative erythropoietin; hemodilution was used in 9 patients and 3 had Cell Saver-generated autotransfusions. Median preoperative hemoglobin was 12.5 g/dL (range 9.5 to 14.4 g/dL) and median postoperative hemoglobin was 10.4 g/dL (range 9 to 12.4 g/dL). In-hospital mortality was 0%. One patient required re-exploration for decreasing hemoglobin and refusal of transfusion; a total of 11 complications developed in 7 other patients (5 wound infection/breakdown, 1 urinary tract infection, 1 ileus, 1 nausea/vomiting, 1 lymphedema, 1 ascites, and 1 ARDS). Median hospital stay was 7 days (range 4 to 23 days). Pancreatic and liver resection can be done safely in selected JW patients who refuse blood products by using a variety of blood-conservation techniques to help spare red cell mass.


Is waking electroencephalographic activity a predictor of daytime sleepiness in sleep-related breathing disorders?
No data are available in the literature assessing the potential use of waking electroencephalographic (EEG) activity in the detection of excessive daytime sleepiness (EDS) in patients with sleep-related breathing disorders (SRBD). The aim of this study was to evaluate whether waking EEG spectral power reflects the level of EDS in SRBD patients. The study was performed in 48 patients in whom quantitative EEG analysis, including the alpha attenuation coefficient (AAC), was performed. Sleepiness was assessed by the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, the Visual Analogue Scale and the maintenance of wakefulness test. Although AAC and EEG spectral power tended to vary throughout the day, none of these variations correlated with EDS measures. Waking EEG measures were not different between snorers and apnoeic patients. Compared to nonsleepy patients, sleepy patients had greater theta and slow alpha powers, but the differences did not reach statistical significance. The EEG slowing was independent of hypoxaemia, severity of SRBD, or degree of sleep disruption. The authors conclude that waking electroencephalographic measures are not sensitive enough to predict variation in alertness or to differentiate sleepy from nonsleepy sleep-related breathing disorders patients. The degree of electroencephalographic slowing was related neither to sleep disruption nor to severity of sleep-related breathing disorders.


Botulinum Toxin for Drooling in Adults with Diseases of the Central Nervous System: A Meta-Analysis.
(1) Background: The purpose of this study was to determine whether the drooling of adult patients with diverse central nervous system diseases can be treated with botulinum toxin type A. (2) Methods: The Cochrane Library, MEDLINE, and Embase were all searched for studies that fit the inclusion criteria. The patients in the studies had to be adults (>18 years old), and the studies had to be randomized placebo-controlled trials, controlled trials, or prospective studies. Each study had to have enough quantifiable data available for meta-analysis. The primary outcome measure was the Drooling Severity and Frequency Scale (DSFS). (3) Results: The meta-analysis comprised three studies. A statistically significant difference in DSFS score between the treatment and control groups was observed in the meta-analysis, with an overall standardized mean difference of -0.9377 (95% CI, -1.2919 to -0.5836; p < 0.0001). A total of seven studies were ineligible for inclusion in the meta-analysis and were only assessed as qualitative data. All qualitative studies showed a significant reduction in DSFS score a few weeks or months after the injection of botulinum toxin. (4) Conclusions: Botulinum toxin type A is safe and effective as a treatment for drooling in adult patients with central nervous system diseases.


The quick-read C-reactive protein test for the prediction of bacterial gastroenteritis in the pediatric emergency department.
To determine the clinical usefulness of the bedside Quick-Read (QR) C-reactive protein (CRP) test for predicting bacterial gastroenteritis in the pediatric emergency department. We tested for CRP in 44 children who presented to the emergency department with gastroenteritis and underwent blood tests and stool culture. C-reactive protein was measured in leftover blood or serum (0.2 mL) using the immunoturbidimetric QR-CRP test kit. Background and outcome data were collected from the files. Pearson correlation, analysis of variance, and logistic regression were used to determine the diagnostic ability of CRP. Stool culture was positive for bacteria in 8 patients. High CRP levels correlated with a greater likelihood of a positive culture; the area under the receiver operating characteristics curve was 0.9427. The CRP values of 95 mg/L or higher had a sensitivity of 87% and a specificity of 91.7% for predicting culture-confirmed bacterial gastroenteritis. The QR-CRP test seems to be a useful predictor of bacterial gastroenteritis in children. It is amenable for use in the emergency department, making it a promising tool for infection control and for aiding physicians in decisions regarding antibiotic treatment. The CRP levels of 95 mg/L or higher during the first 48 hours are suggestive of bacterial disease.


Single ion hydration free energies: a consistent comparison between experiment and classical molecular simulation.
The determination of single ion hydration free energies is troubled by the thermodynamic constraint that only the properties of neutral pairs can be uniquely determined. As such, single ion properties depend on extrathermodynamic information, which can differ between experimental and molecular simulation measurements. This comparison is hampered by the quantum mechanical nature of the proton, the reference ion of choice for developing standard tables, and uncertainty in the experimental reference potential to which properties are measured. We revisit the methodology of Latimer et al. [J. Chem. Phys. 7, 108 (1939)], which extracts single ion properties from neutral pair transfer free energies under the assumption that the Born equation provides an accurate description of the charging of monovalent ions. This methodology permits us to make a consistent comparison between experimental and theoretical values for single ion hydration free energies and gives insight into nonpolar contributions to the ion hydration free energy as well as the potential at the center of a hypothetical uncharged ion.


Cardiac resident macrophages: key regulatory mediators in the aftermath of myocardial infarction.
Acute myocardial infarction (MI) is a prevalent and highly fatal global disease. Despite significant reduction in mortality rates with standard treatment regimens, the risk of heart failure (HF) remains high, necessitating innovative approaches to protect cardiac function and prevent HF progression. Cardiac resident macrophages (cMacs) have emerged as key regulators of the pathophysiology following MI. cMacs are a heterogeneous population composed of subsets with different lineage origins and gene expression profiles. Several critical aspects of post-MI pathophysiology have been shown to be regulated by cMacs, including recruitment of peripheral immune cells, clearance and replacement of damaged myocardial cells. Furthermore, cMacs play a crucial role in regulating cardiac fibrosis, risk of arrhythmia, energy metabolism, as well as vascular and lymphatic remodeling. Given the multifaceted roles of cMacs in post-MI pathophysiology, targeting cMacs represents a promising therapeutic strategy. Finally, we discuss novel treatment strategies, including using nanocarriers to deliver drugs to cMacs or using cell therapies to introduce exogenous protective cMacs into the heart.


[Expressions of differential proteins in the expressed prostatic secretion of patients with III A chronic prostatitis].
To study the expressions of differential proteins in the expressed prostatic secretion (EPS) of patients with III A chronic prostatitis and healthy men. We collected EPS samples from 35 patients with III A chronic prostatitis and 18 age-matched healthy men, and detected the differentially expressed proteins in EPS by MALDI-TOF/MS. Based on the data obtained, we conducted a statistical analysis on the mass-to-charge (m/z) ratios of different proteins and a retrieval analysis on the relevant proteins using the protein database. In the comparative studies of the III A chronic prostatitis patients and healthy men, 5 proteins were detected as at least 2-fold differentially expressed, which were probably brevinin-2Eg, big endothelin-1, alpha-defensin 15, beta-defensin 134 and prostatic steroid-binding protein C2. The m/z ratios were significantly up-regulated in 3 372, 3 487, 425 and 5 325 Da proteins (P < 0.01) and down-regulated in 10631Da (P < 0.01). Proteins are differentially expressed in the EPS of III A chronic prostatitis patients and healthy men, and these proteins may be significantly correlated with the development and progression of III A chronic prostatitis.


Long working hours and psychological distress among school teachers in Japan.
Long working hours have the possibility to influence human health. In Japan, it is well known that teachers have long working hours, and the number of leaves of absence due to mental disorders among public school teachers increased from 2,687 in 2002 to 4,960 in 2012. The aim of this study was to investigate the association between long working hours and psychological distress among school teachers. This cross-sectional study was conducted from mid-July to September in 2013 in Hokkaido Prefecture, Japan. Questionnaires were distributed to 1,245 teachers in public junior high schools. Information about basic characteristics, including working hours, and responses to the General Health Questionnaire-28 were collected anonymously. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for the association between long working hours and psychological distress by gender. Of the 1,245 teachers contacted, 558 (44.8%) responded. After excluding responses with missing data, the final sample included 522 teachers (337 males and 185 females). Psychological distress was identified in 47.8% of males and 57.8% of females. Our results showed a significantly increased risk only in males working >60 hours per week (adjusted OR=4.71 [95% CI 2.04-11.56]) compared with those working ≤40 hours per week. There were no significant associations between long working hours and psychological distress for females. There is a significant association between long working hours and psychological distress in male teachers. However, the causal relationship remains unclear. Further studies such as cohort studies with large sample sizes are needed.


[Chapter 2. Internet of Things help to collect Big Data].
According to the report ?The Internet of Things Market? the number of connected devices will reach 68 billion in 2020. In 2012, the total amount of data was 500 petabytes. So, after the race to increase power computation, now the stake is in the capacity to store all these data in the cloud, to open their access and to analyze these data properly. The use of these data is a major challenge for medical research and public health.


The long-term effect of exposure to respirable particulate matter on the incidence of myocardial infarction: a systematic review and meta-analysis study.
Although several studies have investigated the long-term association of respirable particulate matter (PM ≤ 10 µm) with the incidence of myocardial infarction (MI), this association is inconclusive or even contradictory. This systematic review and meta-analysis study aimed to quantify the long-term effect of exposure to respirable PM on the incidence of MI. To find relevant publications, online databases, including Scopus, PubMed, and Web of Science, were searched on October 10, 2021. A random-effect model was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (95% CI) of MI across studies. Heterogeneity was presented with reporting I2 index. Of 4591 records found in the primary searching, the number of 24 prospective cohort studies with more than 70 million participants was included. The pooled HR (95% CI) of MI per 1 µg/m3 increment of respirable PM was estimated as 1.01 (1.00, 1.01). Subgroup analyses according to aerodynamic diameter of PM showed an only significant stronger risk of MI per 1 µg/m3 increase in PM with aerodynamic diameter < 2.5 µm (HR = 1.01, 95% CI = 1.00, 1.01). No sex difference was found in the association of respirable PM with MI incidence. There was only a significant association among studies defined MI as ICD-10: I21 code (HR = 1.01, 95% CI = 1.00, 1.01) and studies defined MI as ICD-10: I21-22 (HR = 1.02, 95% CI = 1.00, 1.04). No significant publication bias was observed across studies. In conclusion, this study confirms a significant association between long-term exposure to respirable PM air pollution and development of MI.


Bumetanide, spironolactone and a combination of the two, in the treatment of ascites due to liver disease. A prospective, controlled, randomized trial.
There are few studies available comparing the efficacy of loop and distal diuretics and a combination of the two groups, in the treatment of ascites due to liver disease. Thirty-seven nonazotemic cirrhotic patients with ascites were randomly allocated to receive for 2 weeks bumetanide (group A, n = 13), spironolactone (group B, n = 12) or a combination of the two drugs (group C, n = 12) after a 5-day stabilization period. The response to the treatment was 69, 42 and 83% in groups A, B and C, respectively; the difference was not significant. Hypokalemia was seen in 4 patients of group A and mild hyperkalemia in 2 patients of group B. Electrolyte disturbances were minimal in patients of group C. The response to diuretic treatment was prompt in groups A and C. It can be concluded that a combination of loop and distal diuretics is superior to a one-drug regimen in achieving a rapid and better diuretic response with fewer side effects.


Actions of Gila monster venom on dispersed acini from guinea pig pancreas.
Venom from Gila monster (family Helodermatidae) contains a pancreatic secretagogue. In dispersed acini from guinea pig pancreas, the venom increased enzyme secretion to the same extent as did vasoactive intestinal peptide, secretin, or PHI. The abilities of vasoactive intestinal peptide and Gila monster venom to stimulate enzyme secretion were not altered by boiling but were abolished by incubation with trypsin or chymotrypsin. Like vasoactive intestinal peptide, secretin, and PHI, the venom caused a 50- to 60-fold increase in cellular cAMP and inhibited binding of 125I-vasoactive intestinal peptide to its membrane receptors on pancreatic acini. The action of venom on enzyme secretion was inhibited by [Gln9]secretin-(5-27), a vasoactive intestinal peptide receptor antagonist, but was not altered by atropine, a cholinergic receptor antagonist, or by dibutyryl cGMP, a cholecystokinin receptor antagonist. Gila monster venom contained no immunoreactive vasoactive intestinal peptide by radioimmunoassay. These results indicate that venom from Gila monster contains a peptide that can stimulate pancreatic enzyme secretion by interacting with vasoactive intestinal peptide receptors on pancreatic acinar cells and thereby activating adenylate cyclase and increasing cellular cAMP.


Apparent nitrogen digestibility data: AACC-ASTM collaborative study.
Apparent nitrogen digestibility data were obtained from 4 laboratories for 6 protein sources and 2 diet levels, 6 and 10% protein, after a 2-day adaptation period during the AACC-ASTM protein efficiency ratio (PER) and net protein ratio (NPR) collaborative studies. For 5 protein sources fed as 10% of the diet, the interlaboratory variation as measured by coefficient of variation (CV) values was low (1.5-3.5%), indicating high precision of the method. Wheat flour (6% protein diet) had the highest variation and, therefore, the lowest precision (CV of 7.10%). The interlaboratory variation (CV value) for 3 of the 4 laboratories was considerably lower, less than half that for the 4 laboratories. An analysis of variance of apparent nitrogen digestibility data indicated significant (P less than 0.05) effects for the 4-laboratory group due to laboratories and protein diets at both 10 and 6% protein levels, and for the 3-laboratory group at the 10% protein level. The 3-laboratory ANOVA for the 6% diets indicated a significant effect (P less than 0.05) due to diet only.


Infectious arthritis.
Septic arthritis results from invasion of the synovium by microorganisms, and most infectious organisms can cause arthritis. In children, septic arthritis is usually associated with systemic infections such as pneumonia or meningitis; in young adults, gonococcal arthritis is the most common cause; and in the aged, septic arthritis is usually superimposed on chronic joint disease. Underlying rheumatoid arthritis is common, and Dr. Knights stresses the importance of recognizing septic arthritis as a complication of rheumatoid arthritis.


SH3 domains and drug design: ligands, structure, and biological function.
The ligand binding preferences, structural features, and biological function of SH3 (Src homology 3) domains are discussed. SH3 domains bind "core" Pro-rich peptide ligands (7-9 amino acids in length) in a polyproline II helical conformation in a highly conserved aromatic rich patch on the protein surface (approximately 390 A2). The ligands can interact with the protein in one of two orientations, depending on the position (N- vs C-terminal) of ligand residues binding to the SH3 selectivity pocket. Core SH3 ligands are characterized by relatively weak interactions (KD = 5-100 microM) that show little binding selectivity within SH3 families. Higher affinity, more selective contiguous ligands require additional flanking residues that bind to less conserved portions of the SH3 surface, with corresponding increase in ligand size and complexity. In contrast to peptide ligands, protein ligands of SH3 domains can exploit multiple discontiguous interactions to enhance affinity and selectivity. A protein-SH3 interaction that utilizes unique interactions may permit the design of small high affinity SH3 ligands. At present, the extended nature of the binding site and homologous nature of the core binding region among SH3 domains present key challenges for structure-based drug design.


Comparative assessment of selected sugarcane biorefinery-centered systems in Brazil: A multi-criteria method based on sustainability indicators.
This work proposes a new sustainability assessment framework aiming to compare selected options of biorefineries subject to provide the same services to a community. At this end, a concept of biorefinery-centered system helps to develop a joint resources and policy-oriented comparison. When an option of biorefinery cannot provide the given amounts of certain services from its own production, it complements its supply portfolio by purchasing the lacking amounts from complementary and conventional production systems. The proposed sustainability assessment framework includes a multi-criteria method used to compare the selected biorefinery options resulting in identifying their respective weaknesses and strengths against categories of criteria. Finally, the methodology helps finding the non-dominated option. Application to selected sugarcane-based biorefineries shows promising results that match with those obtained in a previous work. However, the new methodology allows extended and richer analyses.


The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial.
Antidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints. The first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed. This study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study's results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD. ClinicalTrials.gov, identifier: NCT05524519.


[Influence of epidural ropivacaine in combination with fentanyl for labor analgesia on the clinical outcome of labor].
To investigate the effect of epidural ropivacaine in combination with fentanyl for labor analgesia on the clinical outcome of labor. A retrospective study was conducted involving 281 healthy primiparas, including 106 undergoing spontaneous labor who received epidural 0.15% ropivacaine in combination with fentany (1microg/ml) and 175 without epidural analgesia. The active phase duration, durations of each labor stages, delivery modes, management of labor, postpartum hemorrhage, incidence of fetal distress and asphyxia neonatorum were recorded in the two groups. The visual analogue scale (VAS) was used to assess the pain of uterine contraction, and modified Bromage scoring system applied to evaluate the lower limb motor block. There were no significant differences in the duration of the first, third or the total labor stages between the two groups, but the second labor stage was prolonged in the labor analgesia group. The ratio of spontaneous labor, assisted vaginal delivery, and incidence of asphyxia neonatorum were higher, whereas the duration of the active stage was shortened in the analgesia group. Epidural ropivacaine in combination with fentanyl in labor can decrease the incidence of cesarean section, and the duration of the active stage can be shortened with application of ocytocin.


Acquired immune deficiency syndrome (AIDS). Medical challenge of the 80's.
Although the pathophysiology of acquired immune deficiency syndrome (AIDS) is not completely understood, we know a great deal about its epidemiology, risk factors, clinical manifestations, course, and immunologic features. Clinicians caring for high-risk individuals, particularly those in endemic urban areas, should remain alert for signs and symptoms of opportunistic infections or neoplasms associated with immunosuppression. It is clear that research on AIDS has increased exponentially; both physicians and patients should be encouraged by the fact that the apparent cause of this syndrome has been identified (human T-lymphotropic retrovirus HTLV-III) and that this breakthrough should result in effective therapeutic strategies in the near future.


Reshaping the Amyloid Buildup Curve in Alzheimer Disease? Partial-Volume Effect Correction of Longitudinal Amyloid PET Data.
It was hypothesized that the brain β-amyloid buildup curve plateaus at an early symptomatic stage of Alzheimer disease (AD). Atrophy-related partial-volume effects (PVEs) degrade signal in hot-spot imaging techniques such as amyloid PET. The current study, a longitudinal analysis of amyloid-sensitive PET data, investigated the effect on the shape of the β-amyloid curve in AD when PVE correction (PVEC) is applied. Methods: We analyzed baseline and 2-y follow-up data for 216 symptomatic individuals on the AD continuum (positive amyloid status) enrolled in the Alzheimer's Disease Neuroimaging Initiative (17 with AD dementia and 199 with mild cognitive impairment), including 18F-florbetapir PET, MRI, and Mini Mental State Examination scores. For PVEC, the modified Müller-Gärtner method was performed. Results: Compared with non-PVE-corrected data, PVE-corrected data yielded significantly higher changes in regional and composite SUV ratio (SUVR) over time (P = 0.0002 for composite SUVRs). Longitudinal SUVR changes in relation to Mini Mental State Examination decreases showed a significantly higher slope for the regression line in the PVE-corrected than in the non-PVE-corrected PET data (F1 = 7.1, P = 0.008). Conclusion: These PVEC results indicate that the β-amyloid buildup curve does not plateau at an early symptomatic disease stage. A further evaluation of the impact of PVEC on the in vivo characterization of time-dependent AD pathology, including the reliable assessment and comparison of other amyloid tracers, is warranted.


A DNA-dependent ATPase from T4-infected Escherichia coli. Purification and properties of a 63,000-dalton enzyme and its conversion to a 22,000-dalton form.
A DNA-dependent ATPase with a molecular weight of 63,000 has been purified to near homogeneity from T4-infected Escherichia coli. This enzyme is not present in uninfected E. coli. It is present in E. coli infected with amber mutants of gene 44 or gene 62 and with the data mutant. The enzyme can be eluted from single-stranded DNA-cellulose at NaCl molarities greater than 0.6 M and from ATP agarose with 80 mM MgATP. The enzyme hydrolyzes MgATP or MgdATP to the diphosphates with equal maximum velocities and the Km values are 0.30 and 0.75 mM, respectively. The enzyme hydrolyzes MgCTP with 13% and MgUTP with 7% of the velocity observed with MgATP. Apparent Km values are reported for single-stranded T4 DNA and for a series of synthetic polynucleotides. The 63,000-dalton enzyme can be cleaved proteolytically to an active 22,000-dalton form. This can be demonstrated by storage of infected cells, by mixing of cell extracts, and by inhibition with phenylmethylsulfonyl fluoride. The Mr = 22,000 enzyme cross-reacts with antibody made to the Mr = 63,000 enzyme. This antibody inhibits the 22,000-dalton species. The 22,000-dalton enzyme forms a complex with gene 32 protein in the absence of DNA.


Changes in DWI and MRS associated with white matter hyperintensities in elderly subjects.
To assess normal-appearing white matter (NAWM) characteristics by magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in elderly subjects. The authors studied 60 volunteers (mean age 72.6 years; SD 4.7; range 64 to 84 years) without signs of neurologic illness. They used DWI and spectroscopic imaging to investigate whether there were changes in the NAWM that related to the presence of white matter hyperintensities (WMH). The authors found a correlation (p < 0.001) between the apparent diffusion coefficient in the NAWM and the total volume of WMH. The metabolite ratios N-acetylaspartate/creatine and N-acetylaspartate/choline of the NAWM also correlated significantly with total WMH volume. These correlations were independent of age. Damage associated with WMH is detectable in NAWM.


Postoperative residual neuromuscular blockade is associated with impaired clinical recovery.
In this investigation, we sought to determine the association between objective evidence of residual neuromuscular blockade (train-of-four [TOF] ratio <0.9) and the type, incidence, and severity of subjective symptoms of muscle weakness in the postanesthesia care unit (PACU). TOF ratios of 149 patients were quantified with acceleromyography on arrival to the PACU. Patients were stratified into 2 cohorts: a TOF <0.9 group (n = 48) or a TOF ≥0.9 (control) group (n = 101). A standardized examination determined the presence or absence of 16 symptoms and 11 signs of muscle weakness on arrival to the PACU and 20, 40, and 60 minutes after admission. The incidence of symptoms of muscle weakness was significantly higher in the TOF <0.9 group at all times (P < 0.001), as was the median (range) number of symptoms from PACU arrival (7 [3-6] TOF <0.9 group vs 2 [0-11] control group; difference 5, 99% confidence interval of the difference 4-6) until 60 minutes after admission (2 [0-12] TOF <0.9 group vs 0 [0-11] control group; difference 2, 99% confidence interval of the difference 1-2) (all P < 0.0001). The incidence and severity of symptoms of muscle weakness were increased in the PACU in patients with a TOF <0.9.


Chyluria: is retrograde pyelogram mandatory prior to endoscopic sclerotherapy?
Chyluria is the passage of milky urine due to a lymphourinary fistula secondary to lymphatic stasis caused by obstruction of the lymphatic flow. This can be caused by parasitic or non-parasitic infections. Though chyluria is a commonly encountered entity in clinical practice particularly in developing countries like India, it is rarely discussed in English literature. We report a case of chyluria with right bifid ureter in a 50-year-old male patient who was treated with intrarenal pelvic instillation of 1% silver nitrate (AgNO3) and emphasis on the diagnostic implication of retrograde pyelography prior to endoscopic sclerotherapy in managing chyluria particularly in renal anomalies.


Assessing Infant Feeding Attitudes of Expectant Women in a Provincial Population in Canada: Validation of the Iowa Infant Feeding Attitude Scale.
Maternal attitudes to infant feeding are predictive of intent and initiation of breastfeeding. The Iowa Infant Feeding Attitude Scale (IIFAS) has not been validated in the Canadian population. This study was conducted in Newfoundland and Labrador, a Canadian province with low breastfeeding rates. Objectives were to assess the reliability and validity of the IIFAS in expectant mothers; to compare attitudes to infant feeding in urban and rural areas; and to examine whether attitudes are associated with intent to breastfeed. The IIFAS assessment tool was administered to 793 pregnant women. Differences in the total IIFAS scores were compared between urban and rural areas. Reliability and validity analysis was conducted on the IIFAS. The receiver operating characteristic (ROC) of the IIFAS was assessed against mother's intent to breastfeed. The mean ± SD of the total IIFAS score of the overall sample was 64.0 ± 10.4. There were no significant differences in attitudes between urban (63.9 ± 10.5) and rural (64.4 ± 9.9) populations. There were significant differences in total IIFAS scores between women who intend to breastfeed (67.3 ± 8.3) and those who do not (51.6 ± 7.7), regardless of population region. The high value of the area under the curve (AUC) of the ROC (AUC = 0.92) demonstrates excellent ability of the IIFAS to predict intent to breastfeed. The internal consistency of the IIFAS was strong, with a Cronbach's alpha greater than .80 in the overall sample. The IIFAS examined in this provincial population provides a valid and reliable assessment of maternal attitudes toward infant feeding. This tool could be used to identify mothers less likely to breastfeed and to inform health promotion programs.


Grooming behavior in American cockroach is affected by novelty and odor.
The main features of grooming behavior are amazingly similar among arthropods and land vertebrates and serve the same needs. A particular pattern of cleaning movements in cockroaches shows cephalo-caudal progression. Grooming sequences become longer after adaptation to the new setting. Novelty related changes in grooming are recognized as a form of displacement behavior. Statistical analysis of behavior revealed that antennal grooming in American cockroach, Periplaneta americana L., was significantly enhanced in the presence of odor.


A Review of Recent Advancements in Anti-tubercular Molecular Hybrids.
Tuberculosis (TB) accounts for millions of deaths worldwide every year. Diverse survival strategies adopted by Mycobacterium tuberculosis (Mtb) have substantially hindered the existing anti-TB regimen thereby leading to multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of TB. The steady decrease in current antibiotics' efficacy against these adversities is an indicator that their adequate replenishment in future is almost impossible, placing society on the precipice of a catastrophe. Over the past many years, researchers have been continuously generating new armamentarium of anti- TB drugs by tailoring the properties of available drugs or designing completely new agents. One of these emerging and successful synthetic techniques is molecular hybridization (MH) that involves the integration of different pharmacophoric subunits to form a new prototype with the ability to be recognized by multiple receptors. In most cases, the resultant conjugates have been reported to exhibit superior biological activity profiles relative to their parent molecules which is attributed to their different or dual modes of action. Accordingly, several new effective anti-TB scaffolds have been synthesized using this approach, and are well cited in literature. In this review, we provide a summarized account of the chemical strategies optimistically focused to develop new molecular assemblies for TB via MH approaches. Additionally, the structure activity relationships revealed from different biological assays is systematically discussed.


VR for Vocational and Ecological Rehabilitation of Patients With Cognitive Impairment: A Survey.
Cognitive impairment arises from various brain injuries or diseases, such as traumatic brain injury, stroke, schizophrenia, or cancer-related cognitive impairment. Cognitive impairment can be an obstacle for patients to the return-to-work. Research suggests various interventions using technology for cognitive and vocational rehabilitation. The present work offers an overview of sixteen vocational or ecological VR-based clinical studies among patients with cognitive impairment. The objective is to analyze these studies from a VR perspective focusing on the VR apparatus and tasks, adaptivity, transferability, and immersion of the interventions. Our results highlight how a higher level of immersion could bring the participants to a deeper level of engagement and transferability, rarely assessed in current literature, and a lack of adaptivity in studies involving patients with cognitive impairments. From these considerations, we discuss the challenges of creating a standardized yet adaptive protocol and the perspectives of using immersive technologies to allow precise monitoring, personalized rehabilitation and increased commitment.


[TVT and TOT for surgical correction of female stress urinary incontinence. Comparison between techniques].
Retrospective analysis of a series of patients with stress urinary incontinence that underwent surgery in our department, by means of the TVT and TOT techniques. We evaluate post operative continence, considering "cured" the patient with complete continence and "failure" any type of involuntary stress urine leak, independently of its severity registering the time of its appearance. For this purpose we used the Kaplan-Meier analysis comparing both techniques with the Breslow test. Additionally, postoperative complications were evaluated. 128 patients who underwent surgery by TVT (69 patients, 53.9%) and TOT (59 patients, 46.1%). Mean age was 54.4 years for TVT (95% CI 52.0-56.8) and 59 years for TOT (95% CI 55.9-62.1). Mean follow-up time was 18.7 months for TVT (95% CI 15.6-21.9) and 7.4 months for TOT (95% CI 5.8-8.9). Overall continence rate was 86.7%, 88.4% for TVT and 84.7% for TOT The probability of being continent six months after surgery was 89.1% for TVT and 78.2% for TOT (no significant differences, p = 0.31), with almost all failures within the first six months after surgery. TVT was more frecuently associated with urgency symptoms (33.3%, p = 0.001) and urge incontinence (18.8%,p = 0.16), urinary retention (11.6%, p = 0.38), and prevesical hematoma requiring mesh retrieval. Greater post operative pain was observed with TOT (20.3%, p = 0.005). Our results evidence a similar efficacy with both techniques, with the failures appearing over the first months after surgery. Complications of the voiding urgency type are significantly more frequent with TVT.


Inflating face-capped Pd6L8 coordination cages.
Tritopic metalloligands were used to form two Pd6L8-type coordination cages. With molecular weights of more than 15 kDa and PdPd distances of up to 4.2 nm, these complexes are among the largest palladium cages described to date.


Laparoscopic cholecystectomy for symptomatic gallstones in diabetic patients.
To find out whether diabetes mellitus is a risk factor in patients who undergo laparoscopic cholecystectomy because of symptomatic gallbladder stones. Eight hundred sixty-two patients with symptomatic gallbladder stones underwent laparoscopic cholecystectomy at our institution between January 1993 and July 2000. Age, sex, risk classification of the American Society of Anesthesiologists (ASA), laboratory tests, operative records, morbidity, and length of hospital stay for each patient were analyzed. There were 184 (21%) diabetic and 678 (79%) nondiabetic patients. The ASA class I applied to 534 nondiabetic (control) patients (79%), and ASA class II to 161 diabetic (study) patients (88%). There was no significant difference between the diabetic and nondiabetic patients regarding leukocyte count, bilirubin, or amylase levels. Operative and postoperative complication rates were significantly higher in the diabetic patients. Conversion to open surgery was required in 19 of 678 patients in the control group (2.8%) and 13 of 184 in the study group (7.1%). The operative time and length of hospital stay were not significantly different in the two groups. Although they had the same symptoms and laboratory findings, laparoscopic cholecystectomy in diabetic patients is associated with more morbidity and a higher conversion rate than in nondiabetic patients.


Insights into the mechanism of Rad51 recombinase from the structure and properties of a filament interface mutant.
Rad51 protein promotes homologous recombination in eukaryotes. Recombination activities are activated by Rad51 filament assembly on ssDNA. Previous studies of yeast Rad51 showed that His352 occupies an important position at the filament interface, where it could relay signals between subunits and active sites. To investigate, we characterized yeast Rad51 H352A and H352Y mutants, and solved the structure of H352Y. H352A forms catalytically competent but salt-labile complexes on ssDNA. In contrast, H352Y forms salt-resistant complexes on ssDNA, but is defective in nucleotide exchange, RPA displacement and strand exchange with full-length DNA substrates. The 2.5 A crystal structure of H352Y reveals a right-handed helical filament in a high-pitch (130 A) conformation with P6(1) symmetry. The catalytic core and dimer interface regions of H352Y closely resemble those of DNA-bound Escherichia coli RecA protein. The H352Y mutation stabilizes Phe187 from the adjacent subunit in a position that interferes with the gamma-phosphate-binding site of the Walker A motif/P-loop, potentially explaining the limited catalysis observed. Comparison of Rad51 H352Y, RecA-DNA and related structures reveals that the presence of bound DNA correlates with the isomerization of a conserved cis peptide near Walker B to the trans configuration, which appears to prime the catalytic glutamate residue for ATP hydrolysis.


Central and peripheral sympathetic activation in heart failure.
The sympathetic nervous system overdrive occurring in heart failure has been reported for more than half a century. Refinements in the methodological approaches to assess human sympathetic neural function have allowed during recent years to better define various aspects related to the neuroadrenergic alteration. These include (i) the different participation of the individual regional sympathetic cardiovascular districts at the process, (ii) the role of the central nervous system in determining the neuroadrenergic overdrive, (iii) the involvement of baroreflex, cardiopulmonary reflex, and chemoreflex mechanisms in the phenomenon, which is also closely linked to inflammation and the immune reaction, (iv) the relationships with the severity of the disease, its ischaemic or idiopathic nature and the preserved or reduced left ventricular ejection fraction, and (v) the adverse functional and structural impact of the sympathetic activation on cardiovascular organs, such as the brain, the heart, and the kidneys. Information have been also gained on the active role exerted by the sympathetic activation on the disease outcome and its potential relevance as a target of the therapeutic interventions based on non-pharmacological, pharmacological, and invasive approaches, including the renal denervation, the splanchnic sympathetic nerve ablation, and the carotid baroreflex stimulation. The still undefined aspects of the neurogenic alterations and the unmet goals of the therapeutic approach having the sympathetic activation as a target of the intervention will be finally mentioned.


The effects of supramolecular assembly on exciton decay rates in organic semiconductors.
We present time-resolved photoluminescence measurements on two series of oligo-p-phenylenevinylene (OPV) materials that are functionalized with quadruple hydrogen-bonding groups. These form supramolecular assemblies with thermotropic reversibility. The morphology of the assemblies depends on the way that the oligomers are functionalized; monofunctionalized OPVs (MOPVs) form chiral, helical stacks while bifunctionalized OPVs (BOPVs) form less organized structures. These are therefore model systems to investigate the effects of supramolecular assembly, the effects of morphology, and the dependence of oligomer length on the radiative and nonradiative rates of pi-conjugated materials. The purpose of this work is to use MOPV and BOPV derivatives as model systems to study the effect of intermolecular interactions on the molecular photophysics by comparing optical properties in the dissolved phase and the supramolecular assemblies. A simple photophysical analysis allows us to extract the intrinsic radiative and nonradiative decay rates and to unravel the consequences of interchromophore coupling with unprecedented detail. We find that interchromophore coupling strongly reduces both radiative and intrinsic nonradiative rates and that the effect is more pronounced in short oligomers.


Finite element modelling and simulations in cardiovascular mechanics and cardiology: a bibliography 1993-2004.
The paper gives a bibliographical review of the finite element modelling and simulations in cardiovascular mechanics and cardiology from the theoretical as well as practical points of views. The bibliography lists references to papers, conference proceedings and theses/dissertations that were published between 1993 and 2004. At the end of this paper, more than 890 references are given dealing with subjects as: Cardiovascular soft tissue modelling; material properties; mechanisms of cardiovascular components; blood flow; artificial components; cardiac diseases examination; surgery; and other topics.


Racial discrimination is associated with greater arterial stiffness and carotid intima-media thickness: the ELSA-Brasil study.
The association between racial discrimination and subclinical cardiovascular markers remains under-examined. We aimed to investigate the association of race/skin color and racial discrimination with pulse wave velocity (PWV) and carotid intima-media thickness (c-IMT) in the Brazilian context. We used data from 13,284 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline with information of PWV and 9850 for c-IMT. Self-reported race/skin color and perceived racial discrimination were the exposures. PWV and c-IMT were used continuously and categorizing according to cutoff that indicates increased cardiovascular risk. Linear and logistic regression models were used. Experience of racial discrimination was reported by 7% of total participants, but this prevalence was much higher among Blacks than Browns (PWV sample: 31,9% vs. 6,1%; c-IMT sample: 33,7% vs. 6,8%). After adjustments for age, sex, and research center, Blacks and Browns presented higher means of PWV and c-IMT and had greater chances of PWV>10 m/s and c-IMT≥75th percentile than Whites. The magnitude of all these associations were higher among Blacks and Browns with racial discrimination. In final models adjusted for education this pattern of association remained the same, although an attenuation in the magnitude of the association has been observed. Blacks and Browns presented worse profiles of subclinical cardiovascular markers compared to Whites and those exposed to racial discrimination seem to have an additional cardiovascular risk.


Pollination Mode and Mating System Explain Patterns in Genetic Differentiation in Neotropical Plants.
We studied genetic diversity and differentiation patterns in Neotropical plants to address effects of life history traits (LHT) and ecological attributes based on an exhaustive literature survey. We used generalized linear mixed models (GLMMs) to test the effects as fixed and random factors of growth form, pollination and dispersal modes, mating and breeding systems, geographical range and habitat on patterns of genetic diversity (HS, HeS, π and h), inbreeding coefficient (FIS), allelic richness (AR) and differentiation among populations (FST) for both nuclear and chloroplast genomes. In addition, we used phylogenetic generalized least squares (pGLS) to account for phylogenetic independence on predictor variables and verify the robustness of the results from significant GLMMs. In general, GLMM revealed more significant relationships among LHTs and genetic patterns than pGLS. After accounting for phylogenetic independence (i.e., using pGLS), FST for nuclear microsatellites was significantly related to pollination mode, mating system and habitat. Plants specifically with outcrossing mating system had lower FST. Moreover, AR was significantly related to pollination mode and geographical range and HeS for nuclear dominant markers was significantly related to habitat. Our findings showed that different results might be retrieved when phylogenetic non-independence is taken into account and that LHTs and ecological attributes affect substantially the genetic pattern in Neotropical plants, hence may drive key evolutionary processes in plants.


Intracarotid L-arginine reverses motor evoked potential changes in experimental cerebral vasospasm.
To investigate motor evoked potentials during short term L-arginine infusion in cerebral vasospasm after experimental subarachnoid hemorrhage. Three groups were designated for this study: control group, subarachnoid hemorrhage-saline infusion group, and subarachnoid hemorrhage-L-arginine infusion group. A subarachnoid hemorrhage was created by intracisternal injection of autologous blood in New Zealand rabbits. At the fourth day of subarachnoid hemorrhage, latency and amplitude of motor evoked potentials were recorded during intracarotid saline and L-arginine infusion, and compared with motor evoked potential parameters of the control group. Motor evoked potential latencies were increased, and amplitudes were decreased in all animals before saline and L-arginine infusion on the fourth day of subarachnoid hemorrhage. A decrease in latencies as well as an increase in motor evoked potential amplitudes was observed with short-term intracarotid L-arginine infusion. Intracarotid short term L-arginine infusion significantly improves motor evoked potential parameters after experimental subarachnoid hemorrhage.


Change of apparent stoichiometry of proximal-tubule Na(+)-HCO3- cotransport upon experimental reversal of its orientation.
Electrogenic cotransport of Na+ with HCO3- has been reported in numerous tissues. It has always been shown with a net transfer of negative charge, but in some situations achieves net outward transport of both species with a stoichiometry of at least three HCO3- ions per Na+ ion (3:1), and in other situations achieves net inward transport of both species and has a stoichiometry of at most two HCO3- ions per Na+ ion (2:1). This suggests either that there may be more than one protein responsible for Na(+)-HCO3- cotransport in different tissues or that if there is a single protein, its stoichiometry may differ depending on the orientation of net transport. The present study, using conventional or double-barreled ion-selective microelectrodes to follow basolateral membrane potential and intracellular pH or Na+ activity in Necturus proximal convoluted tubule in vivo, shows that the orientation of the basolateral Na(+)-HCO3- cotransporter can be reversed upon switching from a perfusate simulating normal acid-base conditions to one that imposes peritubular isohydric hypercapnia. Moreover, accompanying the reversal of orientation is a change of apparent stoichiometry from 3:1 to 2:1. Given that the observed change of orientation and accompanying change of apparent stoichiometry occur within seconds and in the same preparation, these results suggest that a single transport protein is responsible for both types of behavior.


Effects of dopamine and serotonin on eructation rate and ruminal motility in sheep.
The relationships between forestomach motility and eructation rate were studied during dopamine infusion (2 sheep) and serotonin infusion (2 sheep). The sheep were chronically fitted with strain gauges on the reticulorumen and with a cannula in the dorsal sac of the rumen. A tracheotomy was performed to intercept the eructated gases and to permit measurement of their volume. To maintain a regular rate of eructation during the control periods, experiments were performed with a moderately increased intraruminal pressure obtained by continuous ruminal insufflation of nitrogen. Dopamine and serotonin were infused (IV for 10 minutes) at rates of 25, 50, and 100 micrograms/kg/min and 4, 8, and 16 micrograms/kg/min, respectively. Dopamine and serotonin both decreased the frequency of primary contractions. Dopamine reduced the amplitude of secondary contractions, whereas serotonin increased the forestomach tone and suppressed secondary contractions which were replaced by unpropagated eructative contractions. These motility changes were associated with a decrease in eructation rate during dopamine infusion and an increase in the eructation rate during serotonin infusion. After dopamine infusion was stopped, rebounds of eructation rate and rumen motility were observed which disappeared when a constant intraruminal pressure was maintained, indicating that the rumen reacts to its own distention. Sulpiride, but not phentolamine or propranolol, blocked the effects of dopamine. The effects of serotonin were abolished by methysergide, but were unaffected by imipramine. Therefore, seemingly dopamine acts through specific dopaminergic receptors and serotonin impringes on smooth muscle serotoninergic receptors. Finally, the use of dopamine and serotonin revealed that close relationships exist between the eructation rate and the pattern of ruminoreticular motility which may be preponderant against the cardia tone in the elimination of ruminal gases.


Enhancement of mouse natural killer cell activity by type II interferon.
It is likely that interferons are key molecules in the physiological regulation of natural killing (NK) activity. This assumption is based on the strong enhancing effect exerted by type I interferon on NK cells. The aim of this study was to examine whether type II interferon, released upon activation of T lymphocytes by a mitogen, had the same enhancing effect. Crude PHA-induced interferon was purified on affinity chromatography columns (Blue Sepharose), and the eluted fractions were tested in parallel for antiviral activity and for in vitro boosting effect on spleen cell natural cytotoxicity. We found that both activities were unseparable. Acid pretreatment of purified type II interferon, as well as addition of anti-type II interferon serum, greatly decreased the enhancement of the spleen cell cytotoxic response. Responder cells to type II interferon are NK cells (surface Ig-negative, Thy-1-negative, devoided of acid Fc receptors) as assessed by classical spleen cell fractionation procedures based on cell surface markers. Comparison between the dose-response curves obtained with type I and type II interferons suggest that both interferon preparations stimulate NK activity in a comparable manner. We could conclude that interferon molecules (type I as well as type II) display a positive immunoregulatory function on NK cells.


N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules.
Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.


Dietary diversity and food intake of urban preschool children in North-Western Sri Lanka.
Childhood malnutrition, associated with poor diet, is a clear public health threat in Sri Lanka, with high rates of under-nutrition and micronutrient deficiencies coupled with the growing risk of overweight/obesity in urban locations. This study explored the dietary diversity and food intake of urban living Sri Lankan preschool children. A cross-sectional analysis of the baseline data from a cohort study was conducted with parents/caregivers of children aged 2-6 years, from 21 preschool centres in Kurunegala District, Sri Lanka. Demographic and socio-economic factors, dietary diversity score (DDS) (n = 597) and food intake (n = 458) (using a food frequency questionnaire) were assessed. Children had a mean DDS of 4.56 ± 0·85 out of 9, with most (91.1%) in the medium DDS category (DDS of 3.1-6.0), consuming rice as most common food. Lentils were consumed more than any meat or alternative food groups at all DDS levels. Child DDS differs with parent/caregiver age and ethnicity. Mean daily intakes of fruit (1.02) and vegetables (0.84) servings align with approximately half of national recommendations, with less than 20% of children meeting daily recommendations. More than one-third consumed sugary snacks and confectionaries daily and 1 in 10 had them twice a day. Around 40% reported watching television while eating the evening meal. Despite the majority having reasonable DDSs (medium category), findings highlighted inadequate intakes of fruits and vegetables, excessive intakes of sugary snacks and unhealthy dietary and social behaviours, suggests the need for population-based interventions to promote healthier dietary habits.


Versatile and declarative dynamic programming using pair algebras.
Dynamic programming is a widely used programming technique in bioinformatics. In sharp contrast to the simplicity of textbook examples, implementing a dynamic programming algorithm for a novel and non-trivial application is a tedious and error prone task. The algebraic dynamic programming approach seeks to alleviate this situation by clearly separating the dynamic programming recurrences and scoring schemes. Based on this programming style, we introduce a generic product operation of scoring schemes. This leads to a remarkable variety of applications, allowing us to achieve optimizations under multiple objective functions, alternative solutions and backtracing, holistic search space analysis, ambiguity checking, and more, without additional programming effort. We demonstrate the method on several applications for RNA secondary structure prediction. The product operation as introduced here adds a significant amount of flexibility to dynamic programming. It provides a versatile testbed for the development of new algorithmic ideas, which can immediately be put to practice.


[Therapeutic effects of cryoablation, radiofrequency ablation, and microwave coagulation against VX2 liver cancer: a comparative study in rabbits].
To Compare the therapeutic effects of cryocareTM cryoablation, radiofrequency ablation(RFA), and and microwave coagulation (MCT) in rabbits with VX(2) liver cancer. Forty-five rabbits with VX(2) liver cancer were randomly and equally allocated into 5 groups to receive treatment with cryocare cryoablation (group A), radiofrequency ablation (group B), microwave coagulation (group C), surgical resection (group D) and control group (group E), respectively. The residual tumor tissues and metastasis (intrahepatic, lung, abdominal lymphoid node, and abdominal implantation) were observed after the treatments, with also detection of soluble interleukin-2 receptor ( sIL-2R) and recording of the survival time of the rabbits. Significant differences were found in the occurrence of tumor residue (chi(2)=20.700, P=0.0000), intrahepatic metastasis (chi(2)=15.652, P=0.0004), and abdominal implantation tumor (chi(2)=13.894, P=0.0008) between the 5 groups, but not in lung and abdominal lymph node metastasis. sIL-2R levels differed significantly only after but not before the treatments (F=31.58, P=0.000) between groups A to D and group E (t=10.119, P=0.000). The treatments in groups A to D all resulted in prolonged survival of the rabbits as compared with the control (F=73.084, P=0.000), and cryocareTM cryoablation and surgical resection showed similarly better effect than RFA and MCT. Cryocare cryoablation can be more effective than RFA and MCT in reducing tumor residue and metastasis and prolonging the survival time of rabbits with VX(2) liver cancer, and RFA and MCT are comparable for their therapeutic effects.


The profile of leucocytes, CD3+, CD4+, and CD8+ T cells, and cytokine concentrations in peripheral blood of children with acute asthma exacerbation.
Objective To determine the leucocyte profile and cytokine concentrations in the peripheral blood of children with an acute asthma exacerbation (AAE). Methods This descriptive, cross-sectional study enrolled paediatric patients admitted to hospital for AAE. The severity of AAE was assessed using the paediatric asthma score (PAS). Peripheral blood samples were collected for automatic quantification of white blood cell counts, CD3+, CD4+, and CD8+ T cells populations by flow cytometry and cytokine concentrations by flow cytometry-assisted immunoassay. Results A total of 127 children with AAE and 30 healthy control subjects were included in the study. The proportion of paediatric patients with decreased CD3+, CD4+ and CD8+ T cells was significantly higher in those with severe AAE compared with those with mild-to-moderate AAE. The concentrations of interleukin (IL)-2, IL-8, IL-12, and IL-4 in paediatric patients with rhinovirus infection were significantly higher than in those without rhinovirus infection. IL-2, IL-4, IL-6, TNF-α and GM-CSF concentrations during AAE were significantly lower than control. IL-5 and IL-13 concentrations during AAE were significantly higher than control. Conclusions The decrease of CD3+, CD4+, CD8+ T cells and IL-2, IL-4, IL-6, TNF-α, and GM-CSF combined with the increase of IL-5 and IL-13, were associated with AAE in children with asthma.


APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL.
Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. Here we report a C-to-T single nucleotide transition that occurs as a somatic mutation in noncoding sequences 4 kb upstream of the transcriptional start site of the LMO1 oncogene in primary samples from patients with T-cell acute lymphoblastic leukaemia. This single nucleotide alteration conforms to an APOBEC-like cytidine deaminase mutational signature, and generates a new binding site for the MYB transcription factor, leading to the formation of an aberrant transcriptional enhancer complex that drives high levels of expression of the LMO1 oncogene. Since APOBEC-signature mutations are common in a broad spectrum of human cancers, we suggest that noncoding nucleotide transitions such as the one described here may activate potent oncogenic enhancers not only in T-lymphoid cells but in other cell lineages as well.


Value of three-dimensional visualization of preoperative prostatic magnetic resonance imaging based on measurements of anatomical structures in predicting positive surgical margin after radical prostatectomy.
Positive surgical margin (PSM) or apical positive surgical margin (APSM) is an established predictive factor of biochemical recurrence or disease progression in prostate cancer (PCa) patients after radical prostatectomy. Since there are limited usable magnetic resonance imaging (MRI)-based models, we sought to explore the role of three-dimensional (3D) visualization for preoperative MRI in the prediction of PSM or APSM. From December 2016 to April 2022, 149 consecutive PCa patients who underwent radical prostatectomy were retrospectively selected from the Second Affiliated Hospital of Dalian Medical University. According to the presence of PSM or APSM, patients were divided into a PSM group (n=41) and a without PSM group (n=108) and into an APSM group (n=33) and a without APSM group (n=116). Twenty-one parameters, including prostate apical shape, PCa distance to the membranous urethra, and pubic angle, were measured on 3D visualization of MRI. The development of the nomogram models was built by the findings of multivariate logistic regression analysis for significant factors. To predict the probability of PSM, a longer PCa distance to the membranous urethra (OR=0.136, p=0.019) and the distance from the anterior peritoneum to the anterior border of the coccyx (work space AP, OR=0.240, p=0.030) were independent protective factors, while a type 3 prostate apical shape (OR=8.262, p=0.025) and larger pubic angle 2 (OR=5.303, p=0.029) were identified as independent risk factors. The nomogram model presented an area under the curve (AUC) of the receiver operating characteristic curve (ROC) of PSM of 0.777. In evaluating the incidence of APSM, we found that the distance to the membranous urethra (OR=0.135, p=0.014) was associated with a low risk of APSM, while larger pubic angle 1 (OR=4.666, p=0.043) was connected to a higher risk of APSM. The nomogram model showed that the AUC of APSM was 0.755. As 3D visualization for preoperative MRI showed good performance in predicting PSM or APSM, the tool might be potentially valuable, which also needs to be validated by multicenter, large-scale, prospective studies.


Reciprocal translocation associated with multiple exostoses in seven members of a three generation family and discovered through an infertile male.
We report a four generations family with multiple exostoses segregating with a reciprocal translocation t(8;19)(q24.11;q13.13) in 8 members of three generations. FISH investigations detected a breakage of the dosage-sensitive EXT1 gene. Although three members of the family died perinatally from unknown causes and one carrier had four spontaneous abortions, the translocation was discovered only when the cytogenetic analysis was requested in an affected male because of oligozoospermia. In fact, it is well known that infertile males may be carriers of reciprocal or Robertsonian translocations with a higher frequency than the general population. This family stresses the importance of requesting the cytogenetic analysis in all cases in which a dominant disease segregates with repeated miscarriages and/or newborn deaths of unknown cause.


Attitudes of Saudi parents toward behavior management techniques in pediatric dentistry.
The purpose of this study was to investigate the attitudes of the Saudi parents toward the different behavior management techniques (BMT) used in pediatric dentistry and assess the factors affecting such attitudes. Two videotapes, each containing 10 BMT, were produced, one with and the other without explanation and objectives of each technique. Parents (N = 133) watched the videotapes as individuals or in groups and rated the acceptability of each BMT. The results indicated that generally Saudi parents readily accept most BMT. Informed parents reported higher acceptance levels of BMT than the uninformed parents (F = 23.975, P = .0001). Group viewers reported less acceptance levels than individual viewers (F = 46.940, P = .001). The tell-show-do, positive reinforcement, and distraction were the most readily acceptable techniques, while parent separation, physical restraint, hand over mouth, and voice control were the least accepted techniques. Generally Saudi parents accepted most of the BMT. Explanation enhanced their level of acceptance.


Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla.
1. The pharmacological activity of dicentrine, isolated from Lindera megaphylla, was determined in rat isolated thoracic aorta, guinea-pig isolated trachea and human platelet-rich plasma. 2. Dicentrine was found to be a potent alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline- (pA2 = 8.19 +/- 0.09) or phenylephrine (pA2 = 9.01 +/- 0.10)-induced vasoconstriction. These effects still persisted in denuded aorta. It was less potent than prazosin (pA2 = 10.60 +/- 0.10), but was more potent than phentolamine (pA2 = 7.53 +/- 0.10) or yohimbine (pA2 = 6.20 +/- 0.05). 3. Inositol monophosphate formation induced by noradrenaline (3 microM) in rat thoracic aorta was suppressed by dicentrine (3-10 microM) and prazosin (3 microM). 4. A high concentration of dicentrine (30 microM) did not affect the aortic contraction induced by the thromboxane receptor agonist U-46619 (1 microM), angiotensin II (1 microM), high potassium (60 mM) or carbachol (3 microM). 5. Contraction of guinea-pig trachea caused by histamine or carbachol was slightly inhibited by dicentrine (30 microM), while beta-adrenoceptor relaxation to isoprenaline in trachea was not affected. 6. Aggregation in human platelet-rich plasma induced by adrenaline (10 microM) was blocked by yohimbine (5 microM). A high concentration of dicentrine (greater than 30 microM) caused slight inhibition of aggregation, the release reaction and thromboxane formation. Complete blockade was obtained with 150 microM dicentrine. 7. It is concluded that dicentrine is a potent, selective alpha 1-adrenoceptor antagonist in vascular smooth muscle.


Seasonal diet composition of Pyrenean chamois is mainly shaped by primary production waves.
In alpine habitats, the seasonally marked climatic conditions generate seasonal and spatial differences in forage availability for herbivores. Vegetation availability and quality during the growing season are known to drive life history traits of mountain ungulates. However, little effort has been made to understand the association between plant phenology and changes in the foraging strategies of these mountain dwellers. Furthermore, this link can be affected by the seasonal presence of livestock in the same meadows. The objective of this work was to study the seasonal changes in diet composition of Pyrenean chamois (Rupicapra p. pyrenaica) and its relationship to primary production trends in a Mediterranean alpine environment. Moreover, diet composition in two populations with contrasting livestock pressure was compared in order to study the effect of sheep flocks on the feeding behaviour of chamois. From 2009 to 2012, monthly diet composition was estimated by cuticle microhistological analysis of chamois faeces collected in the eastern Pyrenees. The primary production cycle was assessed by remote sensing, using the Normalized Difference Vegetation Index. Additionally, the diet of sheep sharing seasonally the subalpine and alpine meadows with chamois was analysed. Diet selection of chamois and sheep and their overlap was also assessed. Our results show an intra-annual variation in the diet composition of Pyrenean chamois and demonstrate a strong relationship between plant consumption dynamics and phenology in alpine areas. In addition, Calluna vulgaris, Cytisus spp. and Festuca spp., as well as forbs in the summer, are found to be key forage species for Pyrenean chamois. Furthermore, this study couldn't detect differences between both chamois populations despite the presence of sheep flocks in only one area. However, the detection of a shift in the diet of chamois in both areas after the arrival of high densities of multi-specific livestock suggest a general livestock effect. In conclusion, Pyrenean chamois are well adapted to the variations in the seasonal availability of plants in alpine habitats but could be disturbed by the seasonal presence of livestock. Due to the key plants in their diet, we suggest that population management programmes should focus on the preservation of mixed grasslands composed of patches of shrubs and herbs. The effects of climate change and shrub expansion should be studied as they may potentially affect chamois population dynamics through changes in habitat composition and temporal shifts in forage availability.


[Effect of compound nutrients on acute immobilization and cold water-immersion stress-induced changes of Th1/Th2 cytokines].
To investigate the effect of compound nutrients on Th1/Th2 imbalance caused by changes in cytokines of Th cell subsets, interleukin (IL)-2, IL-6 and TNF-α, in rats with acute immobilization and cold water-immersion stress. Male SD rats were randomly assigned to three groups including normal control group (C), acute stress group (S) and acute stress+compound nutrients group (S+CN). Stress procedure was the acute immobilization and cold water-immersion. The stress rats were fed water (Group S) or compound nutrient liquid (Group S+CN) by a feeding needle 1 week before acute stress, and then restrained and immersed in cold water for 30 min. The control rats were given water in the same way without stress stimulation. The rats were killed and blood samples were collected 0, 30, 60 and 120 min after stress, respectively. Serum was separated by centrifugation and stored at -70 DegreesCelsius until assayed. The serum levels of IL-2, IL-6 and TNF-α were analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. Acute immobilization and cold water-immersion stress reduced IL-2 level, and increased IL-6 and TNF-α level at different time points (0, 30, 60 and 120 min) after stress, which was most obvious at 30 min. Oral administration (gavage) of compound nutrients was found to moderate the acute immobilization and cold water-immersion stress-induced changes in serum IL-2, IL-6 and TNF-α, which was also most significant at 30 min after stress. Complex nutrients can significantly alleviate the changes of Th1/Th2 cytokines in stress rats, including IL-2, IL-6 and TNF-α, which suggests that compound nutrients can improve the immune regulation function of stress rats and restore Th1/Th2 balance. Compound nutrients might enhance the body's anti-stress ability and lighten the stress-related damage, thus being a possible candidate for the therapeutic modulation of stress.


[Prognostic factors in functional outcome after stroke: a review].
Survivors of stroke constitute the largest group of patients receiving rehabilitative therapy. Purpose of this article is to review the prognostic factors which can affect functional outcome after stroke. An accurate prognostic assessment is fundamental after cerebrovascular accident, in order to plan the rehabilitative project and define both early and long-term objectives. We found agreement of opinions about the prognostic value of some factors, whereas three are difference of opinions about other prognostic factors in predicting neurological outcome.


Comparison of severity of illness scores to physician clinical judgment for potential use in pediatric critical care triage.
A pediatric triage tool is needed during times of resource scarcity to optimize critical care utilization. This study compares the modified sequential organ failure assessment score (M-SOFA), the Pediatric Early Warning System (PEWS) score, the Pediatric Risk of Admission Score II (PRISA-II), and physician judgment to predict the need for pediatric intensive care unit (PICU) interventions. This retrospective cohort study evaluates three illness severity scores for all non-neonatal pediatric patients transported and admitted to a single center in 2006. The outcome of interest was receipt of a PICU intervention (mechanical ventilation, acute dialysis, depressed consciousness, or persistent hypotension). Predictive ability was assessed using receiver operating curves (ROCs). Of 752 patients admitted to the hospital, 287 received a PICU intervention. Median scores for all tools were significantly higher for children receiving an intervention than for those who did not. ROCs showed PEWS had the least discriminatory ability, followed by PRISA-II and pediatric M-SOFA. No value of the pediatric M-SOFA produced both positive and negative predictive values better than clinician judgment. No score had a clinically acceptable discriminate ability to predict patients who required a PICU intervention from those who did not. Physician judgment outperformed all three triage scores.


Detection of MYD88 L265P and WHIM-like CXCR4 mutation in patients with IgM monoclonal gammopathy related disease.
A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort. We performed real-time allele-specific-polymerase chain reaction and Sanger sequencing to explore the presence of MYD88 L265P and WHIM-like CXCR4 mutations. One hundred and twelve patients (64 male and 48 female patients) were included in this retrospective study. The median age at diagnosis was 62 years (range, 30-84 years). In total, 64 patients (57.1%) carried the MYD88 L265P mutation and 14 patients (12.5%) carried the CXCR4 WHIM-like mutation. We identified the MYD88 L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1). The mutation was absent in five patients with Cryoglobulinemia, two with primary cold agglutinin disease and one with MM. The CXCR4 WHIM-like mutation was present in 10/42 patients with WM, 3/41 with NHL (1 DLBCL, 1 SMZL, and 1 NMZL), and 1/18 patients with IgM MGUS. Among the patients with NHL, those with the mutated MYD88 L265P genotype were younger and had lower level of IgG and IgA than the patients with the wild-type genotype. Patients with the mutated MYD88 L265P genotype with WM and MZL were compared. More male patients, higher levels of IgM and lower levels of LDH were found in the WM group. There was no significant difference in overall survival between the two groups. We present a study of the prevalence of the MYD88 L265P mutation and CXCR4 WHIM-like mutation in IgM RD. The MYD88 L265P mutation may play a key role in the pathogenesis of IgM monoclonal gammopathies. It would be interesting in the future to use MYD88 mutation status to differentiate among diseases.


The nutritive value and some biochemical aspects of single cell protein obtained from "Saccharomyces, sp.", in rat feeding.
The authors have studied the biological value (BV) of Single Cell Protein (SCP) obtained from "Saccharomyces, sp." and the probable alterations among the values of uric acid, urea, total protein (Pt) and albumin (Ab) in the serum, and among hepatic content of DNA, RNA, Pt and total lipids in Wistar male rats. The animals were fed "ad libitum" with an experimental diet containing 25% of protein of SCP (EG-25), and a control diet containing 25% protein of casein (CG-25) during 9 weeks from weaning (28 days old). The BV was significantly smaller in EG-25. The serum and urine values of uric acid were higher in the EG-25 and these data suggest homeostasis. The urea contents were higher in CG-25. The Pt and Ab did not differ. The hepatic variables: the total lipids, the cell weight, the relation protein/nucleus and the liver weight in relation to the body weight were higher in EG-25. The DNA, RNA and number of hepatic cells were lower to EG-25 as compared to CG-25 (p less than 0.05). The results also indicated that the BV of SCP at 25% was inferior to that of casein. The biochemical hepatic results may be attributed to a deficiency in total-S-amino acids in SCP. The protein synthesis in the liver doesn't seem to have suffered any alterations by the ingestion of amino acids present in the casein and in the SCP. Hepatic hypertrophy may have occurred during the acute stage of growth. The protein of SCP may have influenced the speed of cell division.


Case study of hydrogen bonding in a hydrophobic cavity.
Protein internal hydrogen bonds and hydrophobicity determine protein folding and structure stabilization, and the introduction of a hydrogen bond has been believed to represent a better interaction for consolidating protein structure. We observed an alternative example for chicken IL-1β. The native IL-1β contains a hydrogen bond between the Y157 side-chain OηH and I133 backbone CO, whereby the substitution from Tyr to Phe abolishes the connection and the mutant without the hydrogen bond is more stable. An attempt to explain the energetic view of the presence of the hydrogen bond fails when only considering the nearly identical X-ray structures. Here, we resolve the mechanism by monitoring the protein backbone dynamics and interior hydrogen bond network. IL-1β contains a hydrophobic cavity in the protein interior, and Y157 is one of the surrounding residues. The Y157 OηH group introduces an unfavorable energy in the hydrophobic cavity, therefore sequestering itself by forming a hydrogen bond with the proximate residue I133. The hydrogen bonding confines Y157 orientation but exerts a force to disrupt the hydrogen bond network surrounding the cavity. The effect propagates over the entire protein and reduces the stability, as reflected in the protein backbone dynamics observed by an NMR hydrogen-deuterium (H/D) exchange experiment. We describe the particular case in which a hydrogen bond does not necessarily confer enhanced protein stability while the disruption of hydrophobicity must be integrally considered.


Macrophage IL-1β contributes to tumorigenesis through paracrine AIM2 inflammasome activation in the tumor microenvironment.
Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1β production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1β enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer.


Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis.
Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.


Emergency myocardial revascularization for myocardial infarction evolving outside the hospital. A feasible option when thrombolysis and coronary angioplasty have failed.
Most reports on emergency coronary revascularization deal with failed percutaneous transluminal coronary angioplasty (PTCA) or refractory ischemia which developed after hospital admission. The objective of this study was to evaluate the feasibility and prognosis of emergency revascularization for acute myocardial infarction evolving outside the hospital. Between 1974 and 1992 54 cases were included in this study. The patients had both electrocardiographic and clinical evidence of ongoing ischemia. One or more infarct-related obstructed coronary arteries were documented by emergency angiography. Since 1981, the patients have been given urokinase, and, since 1986, they have undergone PTCA initially and, when reperfusion failed, revascularization was started. Overall in-hospital mortality has been 11.1% (6/54). All other patients were discharged in satisfactory condition. Follow-up for periods of up to nearly twenty years has been uneventful with the exception of two late sudden deaths. The above results confirm that emergency coronary revascularization is a therapeutical option worth considering.


Golgi alpha-mannosidase II cleaves two sugars sequentially in the same catalytic site.
Golgi alpha-mannosidase II (GMII) is a key glycosyl hydrolase in the N-linked glycosylation pathway. It catalyzes the removal of two different mannosyl linkages of GlcNAcMan(5)GlcNAc(2), which is the committed step in complex N-glycan synthesis. Inhibition of this enzyme has shown promise in certain cancers in both laboratory and clinical settings. Here we present the high-resolution crystal structure of a nucleophile mutant of Drosophila melanogaster GMII (dGMII) bound to its natural oligosaccharide substrate and an oligosaccharide precursor as well as the structure of the unliganded mutant. These structures allow us to identify three sugar-binding subsites within the larger active site cleft. Our results allow for the formulation of the complete catalytic process of dGMII, which involves a specific order of bond cleavage, and a major substrate rearrangement in the active site. This process is likely conserved for all GMII enzymes-but not in the structurally related lysosomal mannosidase-and will form the basis for the design of specific inhibitors against GMII.


Comparative ultrastructure of fruit plastids in three genetically diverse genotypes of apple (Malus × domestica Borkh.) during development.
Comparative ultrastructural developmental time-course analysis has identified discrete stages at which the fruit plastids undergo structural and consequently functional transitions to facilitate subsequent development-guided understanding of the complex plastid biology. Plastids are the defining organelle for a plant cell and are critical for myriad metabolic functions. The role of leaf plastid, chloroplast, is extensively documented; however, fruit plastids-chromoplasts-are poorly understood, especially in the context of the diverse metabolic processes operating in these diverse plant organs. Recently, in a comparative study of the predicted plastid-targeted proteomes across seven plant species, we reported that each plant species is predicted to harbor a unique set of plastid-targeted proteins. However, the temporal and developmental context of these processes remains unknown. In this study, an ultrastructural analysis approach was used to characterize fruit plastids in the epidermal and collenchymal cell layers at 11 developmental timepoints in three genotypes of apple (Malus × domestica Borkh.): chlorophyll-predominant 'Granny Smith', carotenoid-predominant 'Golden Delicious', and anthocyanin-predominant 'Top Red Delicious'. Plastids transitioned from a proplastid-like plastid to a chromoplast-like plastid in epidermis cells, while in the collenchyma cells, they transitioned from a chloroplast-like plastid to a chloro-chromo-amyloplast plastid. Plastids in the collenchyma cells of the three genotypes demonstrated a diverse array of structures and features. This study enabled the identification of discrete developmental stages during which specific functions are most likely being performed by the plastids as indicated by accumulation of plastoglobuli, starch granules, and other sub-organeller structures. Information regarding the metabolically active developmental stages is expected to facilitate biologically relevant omics studies to unravel the complex biochemistry of plastids in perennial non-model systems.


[Three surgical strategies for the treatment of intercourse-related hematuria in males: A summary of clinical experience].
To summarize the clinical experience in the treatment of sexual intercourse-related hematuria in males using biopsy forceps, electrocoagulation and holmium laser cauterization. From July 2018 to April 2022, we treated 11 male patients with intercourse-related hematuria using biopsy forceps, electrocoagulation and holmium laser cauterization. The patients ranged in age from 29 to 47 years, with clinical manifestations of gross hematuria, blood dripping from the urethral orifice or blood clots in the urine after sexual intercourse or erection, 3 with hemospermia, but none with pain. All the patients received urological imaging examination to exclude lesions in the upper urinary tract and bladder preoperatively. During the operation, varicose vessels were found around the posterior urethral verumontanum under the cystourethroscope in all the cases, 5 with active bleeding in the posterior varicose vessel. The 3 cases with hemospermia first underwent trans-prostatic utricle seminal vesiculoscopy. According to the range and number of varicose vessels, 5 of the patients were treated by electrocoagulation with the resectoscope, 2 by holmium laser cauterization and the other 4 with biopsy forceps to destroy the vascular tissue. After the operation, urinary catheters were retained for 3-7 days, abstinence lasted 30 days, and the patients were followed up for 6 months. The operations were successfully completed in all the cases, 10 with good prognosis and none with recurrence. Occasional postoperative hematuria and blood clots in the urine were observed in 1 of the patients treated by electrocoagulation under the resectoscope, with dysuria at 3 months after operation, who underwent repeated electrocoagulation and experienced no more recurrence thereafter. Different degrees of postoperative urethral irritation and gross hematuria were found in all the cases, which spontaneously disappeared within 1-4 weeks, with no such complications as ED, ejaculation pain, ejaculation difficulty and ejaculation weakness. In the absence of other genitourinary diseases, painless hematuria, blood clots in the urine or even dysuria in males after sexual intercourse can be considered as the results of possible varicose veins around the posterior urethral verumontanum, which can be treated satisfactorily by destroying the vascular tissue with biopsy forceps, electrocoagulation with the resectoscope or holmium laser cauterization according to the location, number and degree of varicose veins.


Transferring interprofessional education concepts across sites - experiences and recommendations for practice.
Aim: Interprofessional education for health care professionals should be anchored at all training and study locations across Germany. In cooperation with the Medical Faculty Mannheim, an education concept trialed there, namely a longitudinal interprofessional learning sequence, was transferred and adapted to the Medical Faculty Dresden as part of the "Operation Team" support program. Here, the structured analysis and evaluation of the knowledge transfer experience is presented from the perspective of the transferee. From these findings, recommendations are derived for the planning of knowledge transfer projects. Methods: The consulting work between the two faculties was listed chronologically including knowledge transfer outcomes and was described and analyzed using the comparative categories identified in sociological systems theory and in the knowledge transfer literature. In addition, knowledge transfer outcomes were categorized according to their use and their relevance to the progress of the project was assessed. Results: The coordination teams initiated 13 consulting sessions, primarily held virtually or by telephone. From these, 36 knowledge transfer outcomes were identified, of which most were of high relevance for the transferee in all use categories. The knowledge transfer core themes were of a strategic (e.g. the consolidation of interprofessional teaching) and content-based/didactic-methodological nature (e.g. interprofessional session design, tutor training). Conclusion: The consulting sessions played a major role in facilitating the establishment of two interprofessional learning sequences and the piloting of the associated sessions at the Dresden site. The recommendations derived for a successful transfer could also be of help for other transfer projects.


In-hospital contact investigation among health care workers after exposure to pulmonary tuberculosis in an intermediate tuberculosis prevalence area: A prospective study.
We carried out in-hospital contact investigations of patients with pulmonary tuberculosis and analyzed the prevalence of latent tuberculosis infection (LTBI) among health care workers (HCWs) after TB exposure. A prospective study was conducted of 872 HCWs who were exposed to 55 index cases diagnosed with active pulmonary TB. HCWs after TB exposure were evaluated both TST and chest X-ray at the time of enrollment and 12 weeks after exposure; 625 HCWs (71.6%) underwent both initial assessments; 41 HCWs (6.6%) had a positive TST result. After 12 weeks, 71.1% of HCWs with initial negative TST (n = 415) underwent a second assessment. Ten HCWs had TST conversion. One HCW (0.2%) developed active pulmonary TB. In multivariable analysis, age over 30 years was associated with TST conversion (p = .02). Point prevalence of latent TB was 6.6%, and incidence of LTBI was estimated as 2.4 per 100 HCWs. Strict infection control measures should be emphasized in intermediate TB-burden, BCG-vaccinated countries, especially in HCWs with high risk for TB exposure.