Long-Term Results of Burch and Autologous Sling Procedures for Stress Urinary Incontinence in E-SISTEr Participants at 1 Site.
We report long-term outcomes in participants in the E-SISTEr (Extended Stress Incontinence Surgical Treatment Efficacy Trial) at 1 tertiary care center who underwent a Burch or a fascial sling procedure for stress urinary incontinence. After receiving institutional review board approval E-SISTEr participants at 1 center who underwent midterm office evaluation in 2010 were further reevaluated at longer term followup by office visits and structured telephone interviews. The telephone interviews were performed by a third party not involved in patient care for those not seen in the last 2 years. Each group received validated questionnaires, including the UDI-6 (Urogenital Distress Inventory-Short Form), the IIQ-7 (Incontinence Impact Questionnaire-Short Form) and the visual analogue quality of life score questionnaire. Failure was measured by Kaplan-Meier curves using time to reoperation for stress urinary incontinence. Of the 29 eligible patients, including 14 treated with a Burch procedure and 15 treated with a sling procedure, 21 had long-term information available, including 11 and 10, respectively. Median followup was 15.1 years (range 11.2 to 16.0). One of the 8 patients was lost to followup, 1 died and 7 were unreachable by telephone. The UDI-6 question 3 score was lower for the 13 patients followed by telephone, including 13 and 7 with a Burch and a sling procedure compared to the 8 seen in clinic, including 5 and 3 with a Burch and a sling procedure, respectively (mean ± SD score 0.3 ± 0.6 vs 1.3 ± 1.1, p=0.0208). The UDI-6 scores were similar for the 2 procedures. Stress urinary incontinence reoperation was performed in 3 cases, including placement of a fascial sling in 1 Burch case. The other 2 cases in the Burch and sling groups received an injectable agent at 11.6 and 13.5 years, respectively. The overall Kaplan-Meier 15-year reoperation-free survival rate was 85.2% (95% CI 60.8-95). In this well characterized cohort with a median followup of 15.1 years there was sustained improvement in continence scores and quality of life related to stress urinary incontinence in each group and the reoperation rate was low.


[Characterization of novel genes regulating adipocyte differentiation].
The mid- and late stages of adipocyte differentiation are known to be regulated by transcription factors such as peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT-box/enhancer binder protein (C/EBP) families. However, events in the early stage of adipocyte differentiation remain largely unknown. To gain insights into the molecular mechanisms underlying the beginning of adipocyte differentiation, we have isolated 102 genes, which are induced at the beginning of the differentiation of mouse 3T3-L1 preadipocytes, using the polymerase chain reaction (PCR)-subtraction method. Of these, 46 appear to be unknown genes. Since rapid amplification of cDNA end (RACE), cDNA library screening, and a genome database search have revealed that two of these genes are novel, we have named them factor for adipocyte differentiation (fad) 24 and fad158. The database research of amino acid sequences revealed that fad24 has a basic leucine zipper motif and an NOC domain, and fad158 has four transmembrane domains and eight leucine-rich repeats. The expression of fad24 and fad158 transiently increased after the addition of adipogenic inducers [insulin, dexamethasone, 3-isobutyl-1-methylxanthine, fetal bovine serum (FBS)]. RNAi-mediated knockdown of fad24 or antisense fad158 inhibited adipogenesis of 3T3-L1 preadipocytes and decreased expressions of PPARgamma and C/EBPalpha. Furthermore, the constitutive overexpression of fad24 or fad158 in the mouse fibroblast cell line NIH-3T3 resulted in adipocyte conversion when stimulated with adipogenic inducers and PPARgamma ligand BRL49653. Moreover, it was found that FAD24 localizes in the nucleus, especially within nuclear speckles and nucleolus, and FAD158 localizes to the endoplasmic reticulum (ER). Taken together, fad24 and fad158 appear to regulate adipocyte differentiation by activating the PPARgamma pathway.


Screen to Save: Results from NCI's Colorectal Cancer Outreach and Screening Initiative to Promote Awareness and Knowledge of Colorectal Cancer in Racial/Ethnic and Rural Populations.
The Center to Reduce Cancer Health Disparities (CRCHD), NCI, implemented Screen to Save, NCI's Colorectal Cancer Outreach and Screening Initiative to promote awareness and knowledge of colorectal cancer in racial/ethnic and rural populations. The initiative was implemented through CRCHD's National Outreach Network (NON). NON is a national network of Community Health Educators (CHE), aligned with NCI-designated Cancer Centers across the nation. In phases I and II, the CHEs focused on the dissemination of cancer-related information and implementation of evidence-based educational outreach. In total, 3,183 pre/post surveys were obtained from male and female participants, ages 50 to 74 years, during the 347 educational events held in phase I. Results demonstrated all racial/ethnic groups had an increase in colorectal cancer-related knowledge, and each group strongly agreed that the educational event increased the likelihood that they would engage in colorectal cancer-related healthful behaviors (e.g., obtain colorectal cancer screening and increase physical activity). For phase II, Connections to Care, event participants were linked to screening. Eighty-two percent of the participants who obtained colorectal cancer screening during the 3-month follow-up period obtained their screening results. These results suggest that culturally tailored, standardized educational messaging and data collection tools are key change agents that can serve to inform the effectiveness of educational outreach to advance awareness and knowledge of colorectal cancer. Future initiatives should focus on large-scale national efforts to elucidate effective models of connections to care, related to colorectal cancer screening, follow-up, and treatments that are modifiable to meet community needs.


Atrial fibrillation epidemiology, disparity and healthcare contacts: a population-wide study of 5.6 million individuals.
Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK. Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF. Results: During a median follow-up of 10.3 years, 199,433(3.6%) patients developed incident AF. Increased risk of hospitalisation for heart failure, cardiovascular conditions and infection was present among patients who later developed AF. Following an AF diagnosis, patients were frequently admitted to the hospital for heart failure, lower respiratory tract infection, chronic obstructive pulmonary disease and ischemic heart disease. One in 5 AF patients died during the first year after diagnosis, and the mortality increased to 42.7% at the fifth year. The excess deaths in AF cases compared to controls may result from cardiovascular diseases, infection and metabolic disorders. Individuals from areas with higher deprivation in socioeconomic and living status had both higher AF incidence and fatality. Interpretation: We observed an elevated risk of hospitalisation for cardiovascular or respiratory diseases among incident AF patients, and the considerable disparity in AF burden by socioeconomic deprivation informs priorities for prevention and provision of patient care. Funding: The study was supported by the GlaxoSmithKline, University College London Hospital and National Institute for Health Research. The funders did not have any role in study design, data collection, data analysis, interpretation, and writing of the report.


Some electrocardiographic patterns predicting sudden cardiac death that every doctor should recognize.
In recent years major advances have been made in the recognition and treatment of candidates to sudden cardiac death. These advances include very sophisticated diagnostic and therapeutic techniques, such as genetic testing and the implantable cardioverter-defibrillator, new knowledge coming from large multicenter trials, particularly about the poor efficacy of so-called "antiarrhythmic" drugs, but also very important advances have been made in improving the diagnostic value of simple techniques such as the twelve-lead electrocardiogram. In this article six different electrocardiographic patterns associated to sudden cardiac death are described. Some patterns, like left ventricular hypertrophy or low voltage in the limb electrocardiographic leads, are frequent and the incidence of sudden death in these patients is relatively low, although clearly higher as compared to individuals with a normal electrocardiogram. On the other hand, other patterns which are rarer (like the long QT syndrome or the syndrome of right bundle branch block and ST segment elevation in V1-V3) are associated to a very high rate of sudden death. Because sudden death can be prevented in many cases, every doctor should be able to recognize these types of electrocardiograms.


The effects of cervical application of inhibitors of inducible nitric oxide synthase, cyclooxygenase-1, and cyclooxygenase-2 on delivery in rats.
To investigate the effect of cervical application of nonselective and selective inhibitors of nitric oxide synthases--N-nitro-L-arginine methyl ester, L-N-iminoethyl-lysine, and aminoguanidine--as well as inhibitors of cyclooxygenases--indomethacin, and nimesulide--on timing of delivery and fetal death and disease in pregnant rats. In a series of experimental protocols, timed-pregnant Sprague-Dawley rats (length of pregnancy, 22 days) were randomly allocated to daily cervical applications of (1) 0.04 mg (n = 6), 0.4 mg (n = 6), 4 mg (n = 6), or 40 mg (n = 6) L-N-iminoethyl-lysine or vehicle (n = 12) on days 19 to 22 of pregnancy; (2) 50 mg aminoguanidine (n = 6), 150 mg aminoguanidine (n = 6), or vehicle (n = 10) on days 19 to 22 of pregnancy; (3) 3 mg indomethacin (n = 6) or vehicle (n = 6) on days 19 to 22 of pregnancy; (4) 12.5 mg/kg nimesulide (n = 8), 25 mg/kg nimesulide (n = 8), 50 mg/kg nimesulide (n = 12), or vehicle (n = 12) on days 19 to 22 of pregnancy and 50 mg/kg nimesulide (n = 23) or vehicle (n = 23) on days 14 to 22 of pregnancy; (5) 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine plus 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine (n = 10), or vehicle (n = 10) on days 14 to 22 of pregnancy. The following variables were evaluated: proportion of animals that were delivered on day 23, time to delivery of the first pup (midnight on day 22 was considered to be 0 hour), number of stillborn pups, and average pup weight of each litter. Unlike L-N-iminoethyl-lysine, aminoguanidine, and indomethacin, 50 mg/kg nimesulide applied on the cervix daily for 8 days significantly increased the proportion of animals that were delivered on day 23 (18 of 23 versus 7 of 23; P =.003) and the time to delivery of the first pup by a mean of 10.8 hours (P <.001). Shorter treatment with nimesulide for 4 days increased only the time to delivery of the first pup at the 25-mg/kg dosage (P =.008). Simultaneous application of aminoguanidine and nimesulide significantly (P =.008) prolonged pregnancy to a degree similar to nimesulide alone. The experiment with N-nitro-L-arginine methyl ester was aborted because of severe maternal side effects. Unlike pups in the L-N-iminoethyl-lysine, aminoguanidine, and nimesulide groups, significantly more pups in the indomethacin group died in utero compared with the control group (36.1% versus 3.1%; P <.001), and the surviving pups had lower birth weights (P <.001). In an animal model, nimesulide was effective in delaying the onset of labor, was well tolerated during pregnancy, and affected cervical ripening directly independent of progesterone withdrawal. Conversely, cervical application of nitric oxide synthase and nonselective cyclooxygenase inhibitors do not extend the duration of pregnancy in the dosages studied, and some are associated with significant adverse effects in the mothers and fetuses.


Treatment Recommendations for Suspected Scapholunate Ligament Pathology.
Background The diagnosis and treatment of scapholunate interosseous ligament (SLIL) pathology is debated and notably variable. This study assessed the influence of diagnostic arthroscopy on treatment recommendations and the interobserver reliability of the arthroscopic classification of SLIL pathology. Methods The influence of diagnostic arthroscopy on treatment recommendations and the reliability of the arthroscopic classification of SLIL pathology were tested in a survey-based experiment. Seventy-seven surgeons evaluated 16 scenarios of people with wrist pain with variation in symptoms, scaphoid shift, time of symptom onset, and MRI appearance of the SLIL. Participants were randomized to view or not to view diagnostic wrist arthroscopy. Factors associated with recommendation for repair, capsulodesis, or tenodesis were analyzed. Results Viewing arthroscopic videos was associated with both offering surgery and a more reconstructive option. Other factors independently associated with recommendation for surgery included greater pain intensity and activity intolerance, women surgeons, an asymmetric scaphoid shift, and a recent onset of symptoms. The interobserver reliability of SLIL classification was slight. Conclusions Diagnostic arthroscopy leads to more surgery, and more invasive surgery, in spite of unreliable assessment of pathology. Clinical Relevance This points to the need to measure the potential benefits and harms of diagnostic wrist arthroscopy among people with wrist pain and no clear diagnosis on interview, examination, and radiographs. Level of Evidence Not applicable.


Sensitivity of a sequential model based on a questionnaire (STOP-Bang vs Dixon) and nocturnal pulse oximetry for screening obstructive sleep apnea in patients with morbid obesity candidates for bariatric surgery.
Obstructive sleep apnea (OSA) has a high incidence in patients with morbid obesity who are candidates for bariatric surgery (BS). Adequate screening would decrease the number of respiratory polygraphies (RPs). To analyze the value of a sequential model consisting of a questionnaire (modified Dixon [DXM] vs STOP-Bang) and nocturnal pulse oximetry in patients who were candidates for BS. A prospective study was conducted from July 1, 2014 to July 1, 2015 on candidates for BS, excluding those who have already undergone RP. questionnaires (Epworth, STOP-Bang, and DXM), anthropometric measurements, RP, and blood and gas tests. The sample was divided into patients with no or mild OSA (no OSA) and those with moderate to severe OSA (AHI>15). A total of 70 patients were analyzed, 46 (65.7%) of them females. Moderate to severe OSA was diagnosed in 26 (37.1%) patients. STOP-Bang and DXM were compared using ROC curves, and greater area under the curve (AUC) was found for the latter (0.873 [0.74 -0.930] vs 0.781 [0.673-0.888]). STOP-Bang had greater sensitivity, 100%, as compared to 73.1% for DXM. ODI3% showed greater diagnostic yield (AUC=0.982 [0.970-1]). Use of the sequential model with STOP-Bang>3, DXM>5, and DXM>3 would have avoided 41 (58.5%), 50 (71.4%), and 41 (58.5%) RPs and 0, 7 (10%), and 0 false negatives, respectively. Use of a sequential model based on the STOP-Bang and nocturnal pulse oximetry is a useful tool for screening OSA in patients with morbid obesity candidates for BS, decreasing the number of RPs.


Surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma with biliary and portal venous tumor thrombi.
We describe the surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma (HCC) associated with biliary and portal venous tumor thrombi. A 67-year-old man was admitted because of jaundice (total serum bilirubin, 6.6 mg/dL). The serum concentration of alpha-fetoprotein was 236.1 ng/mL. The anti-hepatitis C virus antibodies were present in the serum. Computed tomography showed a large hypervascular mass in the right subphrenic region, surrounded by local effusion. Endoscopic retrograde cholangiography revealed dilatation of the left intrahepatic bile duct caused by biliary tumor thrombi extending from the right hepatic duct to the common bile duct. Endoscopic nasobiliary drainage was performed, and the total serum bilirubin level returned to the normal range. Angiography revealed a hypervascular tumor without extravasation of contrast medium in the right lobe and obstruction of the right anterior branch of the portal vein. Right hepatectomy was attempted 15 days after drainage. Severe invasion of the diaphragm by the ruptured HCC was detected. Bleeding of the ruptured HCC stopped spontaneously. Partial resection of the diaphragm was performed, followed by primary suture, without an artificial patch. Tumor thrombectomy was performed from the common bile duct. Macroscopic examination revealed that the ruptured HCC had invaded the diaphragm. Biliary and portal venous tumor thrombi were present. Histopathological examination showed a moderately differentiated HCC with biliary and portal venous tumor thrombi. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Five months after the operation, local and intrahepatic recurrences of HCC were detected. Six months after operation, the patient died of liver failure. In conclusion, the outcome of a patient with diaphragmatic invasion by a ruptured HCC with biliary tumor thrombi was poor, even after curative hepatic resection.


Identifying potential adverse events dose-response relationships via Bayesian indirect and mixed treatment comparison models.
Patients and prescribers need to be fully informed regarding the safety profile of approved medications. This includes knowledge and information regarding whether an adverse event of interest exhibits a potential dose-response relationship. In order to thoroughly evaluate whether an adverse event rate increases with increasing dose level, evidence from multiple clinical trials needs to be combined and analyzed. The various clinical trials that need to be combined often include different dose levels. If one evaluates the dose-response relationship by including only the trials with all of the common dose levels, this will lead to the exclusion of potentially several clinical trials as well as dose levels, and thus the loss of important information. Other methods, such as crudely pooling patients on the same dose level across different studies, are subject to bias due to the breakdown of randomization. It is preferable to include all studies and relevant dose levels, even if all studies do not contain the same dose levels. Bayesian methodology has been shown to be useful in the context of indirect and mixed treatment comparison methods, to combine information from different therapies in different studies in order to make treatment effect inferences. This type of approach is foundational to the models presented here, but instead of modeling different dose arms in different studies, we extend the methodology to allow for assessment of the dose-response relationship across multiple clinical trials. In this paper, we propose three Bayesian indirect/mixed treatment comparison models to assess adverse event dose-response relationships. These three models are designed to handle binary responses and time to event responses. We apply the methods to real data sets and demonstrate that our proposed methods are useful in discovering potential dose-response relationships.


Role of free vascularized bone grafts in the experimentally-induced ischemic necrosis of the femoral head.
In 15 mongrel adult dogs, an ischemic necrosis of the femoral head was produced, following the technique described by Gartsman and colleagues. Five weeks later, a 6- to 8-cm long rib graft was harvested with its vascular bundle and transferred into the previously induced ischemic femoral head. Microsurgical anastomoses were performed for revascularizing the rib graft. Dogs were studied using scintigraphy, blood flow measurements, roentgenograms, angiograms, and histology at four, eight and 12 weeks after grafting. New bone and vascular formation was exhibited throughout the study, as demonstrated by a highly positive scintigraphic activity and the formation of numerous arterial terminal branches arising from the rib graft circulation which entered the femoral head and reached the subchondral plate. The formerly necrotic femoral head bone exhibited osteoblastic activity, viable osteocytes, and well-populated bone marrow. The rib graft was also incorporated into the femoral head. These results suggest that a vascularized bone graft is able to repair a femoral head necrosis, and may be considered a rational approach for clinical purposes.


Prognostic implications of neuropsychological test performance for surgical treatment of epilepsy.
Surgical treatment of epilepsy is undertaken on the basis of prognostically favorable clinical and laboratory data. Analysis of neuropsychological test data obtained preoperatively and postoperatively from 14 surgically treated patients indicates that specific measures of neuropsychological test performance may provide prognostic information aside from the utility of this testing for lateralization and localization. An impairment Index which is derived from the extensive test battery was related to change of seizure frequency. The groups of patients which have an improved or seizure-free status postoperatively also have the least preoperative neuropsychological impairment. The group of patients which did not show improvement of seizure frequency had a younger mean age at onset of seizures (x = 6.7 years), while the group which was rendered seizure free had a later age at onset (x = 17.2 years). There was no relationship for the duration of seizures prior to surgery and the outcome following surgery.


KLF13 influences multiple stages of both B and T cell development.
The Kruppel-like factor, KLF13, is a member of a family of transcription factors shown to be involved in haematopoietic development. Here we show that KLF13 is involved in the development of B and T cells at multiple stages. Expression of KLF13 in the thymus was maximal in the DP population and in KLF13(-/-) deficient mice there was an accumulation of DP thymocytes and reduction of CD4(+)SP cells. Cell-surface expression of CD3(high), CD8, CD5 and HSA were altered on KLF13(-/-) DP cells, consistent with a defect in TCR signalling and at the DP to SP transition in KLF13(-/-) mice. KLF13 is also expressed in peripheral T-cells and peripheral T cell activation was impaired in KLF13(-/-) mice. Analysis of early B cell development in the bone marrow (BM) revealed a partial arrest of B cells at the transition from CD43(+) to CD43(-) pre-B cell, a transition that requires signalling through the pre-BCR. The proportion of IgM(+)/IgD(+) mature B cells was also increased in the BM of the KLF13(-/-) mice. This finding is consistent with a reduction in the strength of BCR signal or an accumulation of recirculating B cells from the periphery. Analysis of splenocytes isolated from KLF13(-/-) mice revealed an increase in the expression of CD21 and CD23 on B220(+) B cells, demonstrating a negative regulatory role for KLF13 in co-regulation of expression of CD21 and CD23. Thus KLF13 is involved at multiple different checkpoints in development that require signalling through the TCR, pre-BCR or mature BCR.


Species-specific positive selection of the male-specific lethal complex that participates in dosage compensation in Drosophila.
In many taxa, males and females have unequal ratios of sex chromosomes to autosomes, which has resulted in the invention of diverse mechanisms to equilibrate gene expression between the sexes (dosage compensation). Failure to compensate for sex chromosome dosage results in male lethality in Drosophila. In Drosophila, a male-specific lethal (MSL) complex of proteins and noncoding RNAs binds to hundreds of sites on the single male X chromosome and up-regulates gene expression. Here we use population genetics of two closely related Drosophila species to show that adaptive evolution has occurred in all five protein-coding genes of the MSL complex. This positive selection is asymmetric between closely related species, with a very strong signature apparent in Drosophila melanogaster but not in Drosophila simulans. In particular, the MSL1 and MSL2 proteins have undergone dramatic positive selection in D. melanogaster, in domains previously shown to be responsible for their specific targeting to the X chromosome. This signature of positive selection at an essential protein-DNA interface of the complex is unexpected and suggests that X chromosomal MSL-binding DNA segments may themselves be changing rapidly. This highly asymmetric, rapid evolution of the MSL genes further suggests that misregulated dosage compensation may represent one of the underlying causes of male hybrid inviability in Drosophila, wherein the fate of hybrid males depends on which species' X chromosome is inherited.


Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care.
The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed.


Antimicrobial Effects of a Hexapetide KCM21 against Pseudomonas syringae pv. tomato DC3000 and Clavibacter michiganensis subsp. michiganensis.
Antimicrobial peptides (AMPs) are small but effective cationic peptides with variable length. In previous study, four hexapeptides were identified that showed antimicrobial activities against various phytopathogenic bacteria. KCM21, the most effective antimicrobial peptide, was selected for further analysis to understand its modes of action by monitoring inhibitory effects of various cations, time-dependent antimicrobial kinetics, and observing cell disruption by electron microscopy. The effects of KCM21 on Gram-negative strain, Pseudomonas syringae pv. tomato DC3000 and Gram-positive strain, Clavibacter michiganensis subsp. michiganensis were compared. Treatment with divalent cations such as Ca(2+) and Mg(2+) inhibited the bactericidal activities of KCM21 significantly against P. syringae pv. tomato DC3000. The bactericidal kinetic study showed that KCM21 killed both bacteria rapidly and the process was faster against C. michiganensis subsp. michiganensis. The electron microscopic analysis revealed that KCM21 induced the formation of micelles and blebs on the surface of P. syringae pv. tomato DC3000 cells, while it caused cell rupture against C. michiganensis subsp. michiganensis cells. The outer membrane alteration and higher sensitivity to Ca(2+) suggest that KCM21 interact with the outer membrane of P. syringae pv. tomato DC3000 cells during the process of killing, but not with C. michiganensis subsp. michiganensis cells that lack outer membrane. Considering that both strains had similar sensitivity to KCM21 in LB medium, outer membrane could not be the main target of KCM21, instead common compartments such as cytoplasmic membrane or internal macromolecules might be a possible target(s) of KCM21.


Psychological outcomes following missed abortions and provision of follow-up care.
This cross-sectional study of 204 women who had experienced a missed abortion, diagnosed at 10-14 weeks of pregnancy, examined the availability and desirability of routine follow-up care, and whether such care is associated with reduced psychological morbidity in the aftermath of miscarriage. Clinically elevated anxiety and depression were observed in 45% and 15% of women, respectively, and the mean score of grief was 2.52 which is similar to that observed in people who suffer death of a close relative. A follow-up appointment after the miscarriage was thought to have been desirable by 92% of women but was offered to only 30%. No significant association between such care and reduced psychological morbidity was identified. However, there were significantly more women with clinically elevated levels of anxiety among those who felt that they were not provided with an opportunity to discuss their feelings during the follow-up, suggesting that such a follow-up either had a deleterious effect on women's psychological state or the distress itself led to such a perception of care. One-third of women in our sample would have liked psychological counselling to help them deal with the emotional aspects of their loss.


Pharmacokinetics of alcuronium in elderly patients undergoing total hip replacement or aortic reconstructive surgery.
The pharmacokinetic behaviour of alcuronium was studied in three patients undergoing resection of an aortic aneurysm, and in another two patients undergoing total hip replacement (group I). A control group of five elderly patients undergoing relatively minor surgery was included (group II). In group I patients, the values of the pharmacokinetic parameters such as plasma clearance, elimination half-life and the apparent volume of distribution of the drug were found to be comparable to those obtained in normal young patients in previous studies. The group II patients, however, were found to have a prolonged elimination half-life as a result of reduced plasma clearance, possibly an age-related effect. The differences between these two groups of patients may be explained by the differences in the extent of haemorrhage and fluid replacement or changes in blood circulation, or both. However, alcuronium must still be used cautiously in both groups of patients, especially in the light of a recent finding that patients undergoing aortic reconstructive surgery have a high frequency of functional renal failure after operation.


[Lactoferrin: biochemistry, physiological roles, and value in human biology].
Lactoferrin and transferrin exhibit very similar structure and biochemical properties but they behave as two distinct antigens and their affinity for ferric ions is not of the same magnitude. The biological functions of lactoferrin are not all well understood. It has strong bacteriostatic properties, it plays a role as a regulator of human granulopoiesis and it is probably involved in the hyposideremia of acute inflammation. Measurement of lactoferrin was first applied in pancreatic juice or duodenal fluid as a diagnostic tool for pancreatic diseases. More recently plasma lactoferrin has been used as an index of total circulating neutrophil pool in hematological disorders and in uremic patients during hemodialysis. Its clinical usefulness is still discussed for the early diagnostic of infectious diseases.


The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease.
Despite the widely held belief that there are no effective medical therapies for peripheral arterial disease (PAD), current data suggest that medical therapies can effectively modify the natural history of atherosclerotic lower extremity arterial occlusive disease. The ideal medical therapy would improve claudication, forestall the onset of limb-threatening events, decrease rates of invasive interventional therapies and improve long-term patient survival. These ideal outcomes might be achieved through the use of smoking cessation interventions, including behavioral and pharmacological therapy, and the administration of antiplatelet and lipid-lowering medications in patients with PAD.


[Somatic disturbances in anorexia nervosa].
This article summarizes a variety of physiological abnormalities found in anorexia nervosa. Metabolic aberrations, endocrine dysfunctions and other physical complications including those of weight-restoring treatments are discussed. Most of them are due to weight loss and the starvation process itself and revert to normal with nutritional rehabilitation.


Associations between serum carotenoid levels and the risk of non-Hodgkin lymphoma: a case-control study.
Limited studies have investigated the effects of serum carotenoids on the risk of non-Hodgkin lymphoma (NHL), and the findings have been inconclusive. This study aims to assess the association between serum total or specific carotenoid levels and NHL risk. This 1:1 matched, hospital-based case-control study enrolled 512 newly diagnosed (within 1 month) NHL patients and 512 healthy controls who were matched by age (±5 years) and sex in Urumqi, China. Serum carotenoid levels were measured by HPLC. Conditional logistic regression showed that higher serum total carotenoid levels and their subtypes (e.g. α-carotene, β-carotene, β-cryptoxanthin and lycopene) were dose-dependently associated with decreased NHL risk. The multivariable-adjusted OR and their 95 % CI for NHL risk for quartile 4 (v. quartile 1) were 0·31 (95 % CI 0·22, 0·48; Pfor trend < 0·001) for total carotenoids, 0·52 (95 % CI 0·33, 0·79; Pfor trend: 0·003) for α-carotene, 0·63 (95 % CI 0·42, 0·94; Pfor trend: 0·031) for β-carotene, 0·73 (95 % CI 0·49, 1·05; Pfor trend: 0·034) for β-cryptoxanthin and 0·51 (95 % CI 0·34, 0·75; Pfor trend: 0·001) for lycopene. A null association was observed between serum lutein + zeaxanthin and NHL risk (OR 0·89, 95 % CI 0·57, 1·38; Pfor trend: 0·556). Significant interactions were observed after stratifying according to smoking status, and inverse associations were more evident among current smokers than past or never smokers for total carotenoids, α-carotene and lycopene (Pfor heterogeneity: 0·047, 0·042 and 0·046). This study indicates that higher serum carotenoid levels might be inversely associated with NHL risk, especially among current smokers.


Efficient iPS cell generation from blood using episomes and HDAC inhibitors.
This manuscript illustrates a protocol for efficiently creating integration-free human induced pluripotent stem cells (iPSCs) from peripheral blood using episomal plasmids and histone deacetylase (HDAC) inhibitors. The advantages of this approach include: (1) the use of a minimal amount of peripheral blood as a source material; (2) nonintegrating reprogramming vectors; (3) a cost effective method for generating vector free iPSCs; (4) a single transfection; and (5) the use of small molecules to facilitate epigenetic reprogramming. Briefly, peripheral blood mononuclear cells (PBMCs) are isolated from routine phlebotomy samples and then cultured in defined growth factors to yield a highly proliferative erythrocyte progenitor cell population that is remarkably amenable to reprogramming. Nonintegrating, nontransmissible episomal plasmids expressing OCT4, SOX2, KLF4, MYCL, LIN28A, and a p53 short hairpin (sh)RNA are introduced into the derived erythroblasts via a single nucleofection. Cotransfection of an episome that expresses enhanced green fluorescent protein (eGFP) allows for easy identification of transfected cells. A separate replication-deficient plasmid expressing Epstein-Barr nuclear antigen 1 (EBNA1) is also added to the reaction mixture for increased expression of episomal proteins. Transfected cells are then plated onto a layer of irradiated mouse embryonic fibroblasts (iMEFs) for continued reprogramming. As soon as iPSC-like colonies appear at about twelve days after nucleofection, HDAC inhibitors are added to the medium to facilitate epigenetic remodeling. We have found that the inclusion of HDAC inhibitors routinely increases the generation of fully reprogrammed iPSC colonies by 2 fold. Once iPSC colonies exhibit typical human embryonic stem cell (hESC) morphology, they are gently transferred to individual iMEF-coated tissue culture plates for continued growth and expansion.


Three-dimensional magnetic resonance angiography in the planning of aneurysm surgery.
Standard planning for intracranial aneurysm surgery relies on the surgeon's intellectual reconstruction of the three-dimensional (3D) surgical field on the basis of a two-dimensional (2D) imaging modality, biplanar cerebral angiography. This method is relatively imprecise, and it relies on previous experience for optimal results. We describe a stereotactic magnetic resonance angiographic (MRA)-guided method based on computer segmentation techniques for the planning of aneurysm surgery that has the potential of bringing a 3D perspective to the lesion. The method has been evaluated retrospectively on 20 surgical patients in whom the aneurysm orientation and relationship to parent vessels were shown to match presurgical 3D stereotactic display. When it is adapted to frameless interactive surgical navigation, this method may become a useful adjunct in the surgical obliteration of these life-threatening lesions.


The progression of an acceptable pulmonary stenosis immediately after total correction of tetralogy of Fallot.
A certain degree of pulmonary stenosis after total correction of tetralogy of Fallot has been considered acceptable. But the long-term outcomes are not well understood. We observed the natural course of immediate pulmonary stenosis and investigated related factors for progression. Fifty-two patients with acceptable pulmonary stenosis immediately after operation were enrolled. Acceptable pulmonary stenosis was defined as peak pressure gradient between 15 and 45 mmHg by Doppler echocardiography. Latent class linear mixed model was used to differentiate patients with progressed pulmonary stenosis, and the factors related to progression were analysed. Pulmonary stenosis progressed in 14 patients (27%). Between the progression group and no progression group, there were no significant differences in operative age, sex, and the use of the transannular patch technique. However, immediate gradient was higher in the progression group (32.1 mmHg versus 25.7 mmHg, p = 0.009), and the cut-off value was 26.8 mmHg (sensitivity = 65.3%, specificity = 65.8%). Main stenosis at the sub-valve was observed more frequently in the progression group (85.7% versus 52.6%, p = 0.027). Despite no difference in the preoperative pulmonary valve z value, the last follow-up pulmonary valve z value was significantly lower in the progression group (-1.15 versus 0.35, p = 0.002). Pulmonary stenosis immediately after tetralogy of Fallot total correction might progress in patients with immediate pulmonary stenosis higher than ≥26.8 mmHg and the main site was sub-valve area.


Training managers for primary health care.
The University of Helsinki has devised a powerful in-service training course for managers of health centres. By working together at the University and their own centres on setting objectives, analysing data and solving problems, the participants greatly enhance their management and teamwork skills.


Comparison of Oncologic Outcomes in Laparoscopic versus Open Surgery for Non-Metastatic Colorectal Cancer: Personal Experience in a Single Institution.
The oncologic merits of the laparoscopic technique for colorectal cancer surgery remain debatable. Eligible patients with non-metastatic colorectal cancer who were scheduled for an elective resection by one surgeon in a medical institution were randomized to either laparoscopic or open surgery. During this period, a total of 188 patients received laparoscopic surgery and the other 163 patients received the open approach. The primary endpoint was cancer-free five-year survival after operative treatment, and the secondary endpoint was the tumor recurrence incidence. Besides, surgical complications were also compared. There was no statistically significant difference between open and laparoscopic groups regarding the average number of lymph nodes dissected, ileus, anastomosis leakage, overall mortality rate, cancer recurrence rate, or cancer-free five-year survival. Even though performing a laparoscopic approach used a significantly longer operation time, this technique was more effective for colorectal cancer treatment in terms of shorter hospital stay and less blood loss. Meanwhile, fewer patients receiving the laparoscopic approach developed postoperative urinary tract infection, wound infection, or pneumonia, which reached statistical significance. For non-metastatic colorectal cancer patients, laparoscopic surgery resulted in better short-term outcomes, whether in several surgical complications and intra-operative blood loss. Though there was no significant statistical difference in terms of cancer-free five-year survival and tumor recurrence, it is strongly recommended that patients undergo laparoscopic surgery if not contraindicated.


Long-lived Plasmodium falciparum specific memory B cells in naturally exposed Swedish travelers.
Antibodies (Abs) are critical for immunity to malaria. However, Plasmodium falciparum specific Abs decline rapidly in absence of reinfection, suggesting impaired immunological memory. This study determines whether residents of Sweden that were treated for malaria following international travel maintained long-lasting malaria-specific Abs and memory B cells (MBCs). We compared levels of malaria-specific Abs and MBCs between 47 travelers who had been admitted with malaria at the Karolinska University Hospital between 1 and 16 years previously, eight malaria-naïve adult Swedes without histories of travel, and 14 malaria-immune adult Kenyans. Plasmodium falciparum-lysate-specific Ab levels were above naïve control levels in 30% of the travelers, whereas AMA-1, merozoite surface protein-142 , and merozoite surface protein-3-specific Ab levels were similar. In contrast, 78% of travelers had IgG-MBCs specific for at least one malaria antigen (59, 45, and 28% for apical merozoite antigen-1, merozoite surface protein-1, and merozoite surface protein-3, respectively) suggesting that malaria-specific MBCs are maintained for longer than the cognate serum Abs in the absence of re-exposure to parasites. Five travelers maintained malaria antigen-specific MBC responses for up to 16 years since the diagnosis of the index episode (and had not traveled to malaria-endemic regions in the intervening time). Thus P. falciparum can induce long-lasting MBCs, maintained for up to 16 years without reexposure.


Recycling of TiO2-containing waste and utilization by photocatalytic degradation of a reactive dye solution.
Recently, the utilization of wastes, recovery of high value-added products from waste, and their use as raw materials in other industries with the logic of industrial symbiosis has become an important issue. In this study, removal efficiency of Reactive Orange 16 (RO16) dye from aqueous solution was studied using TiO2 catalyst recycled from an industrial waste effluent. The recycling of TiO2 waste from a paints manufacturing industry was carried out by sintering the TiO2-containing waste. The catalyst usability of TiO2-containing powder was then investigated in the removal of RO16 dye by photocatalytic oxidation process. In photocatalytic oxidation studies, TiO2/UV and TiO2/UV/H2O2 processes were investigated, where the effect of annealing temperature, the effect of H2O2 concentration, and the adsorption and photocatalytic effects on RO16 dye removal were studied. The results showed that 100% RO16 removal was obtained for the 10 mg/L initial RO16 concentration using the TiO2 (1 g/L)/UV process. At high initial RO16 concentration (50 mg/L), 100% RO16 removal was achieved by adding 10 mM H2O2.


Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use.
Long-acting propranolol (Inderal LA) is a new formulation of propranolol that allows release of the drug in a controlled manner, so that the plasma concentration at 24 hr after dosing is greater with long-acting propranolol than with conventional tablets. A single dose of 160 mg of long-acting propranolol can produce cardiac beta-adrenoceptor blockade throughout a 24 hr period without variability due to multiple peak concentrations. It has been shown that this formulation is as effective in the treatment of angina pectoris, hypertension and hyperthyroidism as the standard formulation. Studies with long-acting propranolol in cardiac dysrhythmias are lacking. This new dosage form would be a means of simplifying dosing regimens and thereby hopefully enhancing patient convenience and compliance.


Serum 25(OH)D and type 2 diabetes association in a general population: a prospective study.
OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30-65 years at baseline (1999-2001), with 4,296 participating in the follow-up examination 5 years later (2004-2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA(1c)) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84-0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86-1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis.


Detection of mycoplasmas infecting cell cultures by DNA hybridization.
Infection of cell cultures by mycoplasmas can be detected and the mycoplasma identified by Southern blot hybridization of the Eco RI-digested DNA of the suspected cell cultures with a nick-translated probe consisting of cloned ribosomal RNA genes of Mycoplasma capricolum. The probe does not hybridize with eukaryotic DNA. The hybridization pattern with mycoplasmal DNA is species specific, enabling the identification of the four most prevalent mycoplasma contaminants, Mycoplasma orale, Mycoplasma hyorhinis, Mycoplasma arginini, and Acholeplasma laidlawii. The test is also very sensitive and can detect as little as 1 ng of mycoplasmal DNA, roughly equivalent to the DNA content of 10(5) mycoplasmas.


Acquired Disorder and Asymmetry in a Domain-Swapped Model for γ-Crystallin Aggregation.
Misfolding and aggregation of proteins occur in many pathological states. Because of the inherent disorder involved, these processes are difficult to study. We attempted to capture aggregation intermediates of γS-crystallin, a highly stable, internally symmetrical monomeric protein, by crystallization under mildly acidic and oxidizing conditions. Here we describe novel oligomerization through strained domain-swapping and partial intermolecular disulfide formation. This forms an octamer built from asymmetric tetramers, each of which comprises an asymmetric pair of twisted, domain-swapped dimers. Each tetramer shows patterns of acquired disorder among subunits, ranging from local loss of secondary structure to regions of intrinsic disorder. The octamer ring is tied together by partial intermolecular disulfide bonds, which may contribute to strain and disorder in the octamer. Oligomerization in this structure is self-limited by the distorted octamer ring. In a more heterogeneous environment, the disordered regions could serve as seeds for cascading interactions with other proteins. Indeed, solubilized protein from crystals retain many features observed in the crystal and are prone to further oligomerization and precipitation. This structure illustrates modes of loss of organized structure and aggregation that are relevant for cataract and for other disorders involving deposition of formerly well-folded proteins.


Long latency auditory evoked responses in ovulatory and anovulatory menstrual cycle.
Central nervous system pathways get influenced by the changing hormonal levels across the menstrual cycle. In an effort to see the effects on the conduction in central auditory pathways we recorded long latency auditory evoked potentials (LLAEPs) across the 4 different phases of the menstrual cycle. 20 females having normal ovulatory menstrual cycles were tested 4 times in a single cycle and LLAEPs were recorded from Cz-A1 and Cz-A2 position with alternating 90 dB sound pressure click stimuli. Twenty age matched control females having anovulatory menstrual cycles were also tested on the corresponding days. All control females were taking oral contraceptive (O.C.) pills. The LLAEPs were compared inter-group wise as well as inter-phase wise for each parameter by using hierarchal ANOVA design and Tukey test was applied to find out the significance level. Peak latencies of waves P2 and N2 were found to be delayed during mid-cycle and relatively reduced mid-luteal phase in ovulatory menstrual cycles. No such response was noticed in oral contraceptive using group. This indicates that normal cyclic variations of female sex hormones especially estrogen and progesterone modify the central processing of the auditory information. Estrogen may be responsible for delaying the conduction by influencing GABA release at the level of polysensory association areas of the brain.


How to Save 1 Million Lives in a Year in Low- and Middle-Income Countries.
Despite major improvements in reducing childhood mortality worldwide, over 5 million pregnancies per year end in stillbirths or neonatal deaths. The vast majority of these deaths occur in low- and middle-income countries. Many of these deaths are preventable with readily available evidence-based care practices. This review focuses on educational programs developed to reduce preventable deaths in newborn infants in low- and middle-income countries, including Essential Newborn Care and Helping Babies Breathe, a simplified version of the Neonatal Resuscitation Program. Innovative pragmatic large-scale trials conducted in the Global Network for Women's and Children's Health Research of the National Institutes of Health in the USA have evaluated these programs in low-resource settings. The results of these studies and the implications for future programs designed to decrease childhood mortality are reviewed.


Metaplastic sarcomatoid carcinoma of the breast with absent or minimal overt invasive carcinomatous component: a misnomer.
Metaplastic carcinomas of the breast are a heterogeneous group of neoplasms ranging from tumors with a predominant component of overt carcinoma and focal mesenchymal differentiation to keratin-positive tumors with pure sarcomatoid morphology. We examined the clinicopathologic features of 22 patients previously diagnosed at M.D. Anderson Cancer Center with metaplastic carcinoma of the breast with pure or almost pure sarcomatoid morphology. Patients were included in the study if their tumors had sarcomatoid morphology and: 1) an invasive carcinomatous component identifiable on hematoxylin and eosin stains comprising less than 5% of the invasive tumor; or 2) associated ductal carcinoma in situ; or 3) immunohistochemical expression of keratin in the sarcomatoid areas. Patients with low-grade fibromatosis-like metaplastic tumors and those who received neoadjuvant chemotherapy were excluded. Axillary lymph node dissection or limited axillary node excision was performed in 17 patients, including 1 patient who had a sentinel lymph node biopsy. Lymph node involvement occurred in only 1 patient and consisted of a single 3.5-mm metastasis. Clinical follow-up was available for 21 patients and ranged from 4 months to 155 months (median follow-up, 35 months). Ten patients experienced local relapse, including 7 of 11 patients treated with breast-conserving surgery, and 9 developed distant metastases, most frequently to the lungs. These findings suggest that metaplastic sarcomatoid carcinomas that lack or have only a minimal overt invasive carcinomatous component have a biologic behavior similar to that of sarcomas. In addition to systemic treatment, early aggressive local therapy is recommended, as these patients have a high rate of local relapse.


Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.
The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.


Silver-Catalyzed Regioselective Fluorination of Carbonyl Directed Alkynes: Synthesis of α-Fluoroketones.
A novel silver-catalyzed fluorination reaction of carbonyl directed alkynes in the presence of N-fluorobenzenesulfonimide and water with high regioselectivities has been developed. The established protocol provides an alternative method for rapid assembly of α-fluoroketone derivatives under simple and mild reaction conditions. The reaction pathway involves a ring closure and opening process for the construction of new C-O and C-F bonds. In addition, a fluorine-containing indanone was observed through further N-heterocyclic carbene catalyzed intramolecular crossed-benzoin reaction of α-fluoroketone.


Valproate and female patients: Prescribing attitudes of Italian epileptologists.
After the European Medicines Agency (EMA) warning on the use of valproate (VPA) in female patients, we explored the antiepileptic drug (AED) prescribing attitudes of Italian epileptologists with regard to sex and VPA use in patients with epilepsy. A specifically designed 30-item questionnaire was distributed at the annual multicenter meeting of the Italian League Against Epilepsy (LICE), held in Rome on January 2018. One hundred and sixty-nine physicians answered the questionnaire. In females, VPA was significantly less prescribed as first-choice AED in childhood absence epilepsy (22% females vs 64% males, p < 0.001), Dravet syndrome (54% vs 71%, p = 0.01), juvenile myoclonic epilepsy (JME) (2% vs 74%, p < 0.001), and undetermined epilepsy (0% vs 32%, p < 0.001). Ninety-six percent of the respondents inform teenage girls of the detrimental effects of intrauterine exposure to VPA; 74% recommend contraceptive measures when prescribing VPA. All the respondents stated that they were aware of the recommendations on VPA in female patients, and 64% claimed to have had difficulties in implementing them. The main challenges were represented by women with JME, who were seizure-free on VPA and failed to respond to levetiracetam and lamotrigine, and by little girls for whom VPA was considered the best choice. According to many Italian epileptologists, the decision to withdraw VPA should be shared with the patient.


Surgical correction of trigonocephaly: theoretical basis and operative procedures.
Trigonocephaly involves premature fusion of both the metopic suture and the sutures in the skull base. Surgical treatment by opening of the prematurely fused metopic suture and expansion of the anterior cranial base by creating "neosutures" was used to treat three children with trigonocephaly. The combination of lateral canthal advancement and radical forehead remodeling achieved excellent results. These procedures can also prevent the development of midface hypoplasia such as hypotelorism. The two younger patients, aged 0 and 6 months, achieved rapid bone growth in the defects and normalization of intercanthal and interpupillary distances. The older patient, aged 8 years, retained some skull defects at follow-up. The optimal age for surgery is 3-6 months, which allows good cosmetic results and minimizes visual repercussions with relatively low perioperative risks.


Treatment of a gastric lactobezoar with N-acetylcysteine.
Lactobezoars are a rare finding with potentially serious sequelae in pediatric patients with feeding intolerance. Aggressive treatment may be preferred to traditional treatments to avoid complications in medically complex patients. In our patient, N-acetylcysteine lavage was a safe and effective alternative that resulted in rapid resolution of his feeding intolerance.


Paper-based lateral flow strip assay for the detection of foodborne pathogens: principles, applications, technological challenges and opportunities.
As a representative colorimetic biosnesor, paper-based LFSA have emerged as a promising and robust tool that can easily and instansly detect the presence of target biological components in food sample. Recently, LFSAs have gained a considerable attention as an alternative method for rapid diagnosis of foodborne pathogens to the conventional culture-based assays such as plate counting and PCR. One major drawback of the current LFSAs for the detection of pathogenic bacteria is the low sensitivity, limiting its practical applications in POCT. Not like many other protein-based biomarkers that are present in nM or pM range, the number of pathogenic bacteria that cause disease can be as low as few CFU/ml. Here, we review current advances in LFSAs for the detection of pathogenic bacteria in terms of chromatic agents and analyte types. Furthermore, recent approaches for signal enhancement and modifications of the LFSA architecture for multiplex detection of pathogenic bacteria are included in this review, together with the advantages and limitations of each techniques. Finally, the technological challenges and future prospect of LFSA-based POCT for the detection of pathogenic bacteria are discussed.


[Effects of solcoseryl on the cerebral blood flow, intracranial pressure, systemic blood pressure and EEG in acute intracranial hypertensive cats (author's transl)].
The experiment was performed on 86 cases under intraperitoneal pentobarbital anesthesia. One balloon was placed in the extradural space of right frontal region, and the other balloon was placed in the left extradural space and the intracranial pressure was measured. A needle was stereotaxically inserted into the subcortical area in order to measure the cerebral blood flow. Systemic blood pressure was recorded by inserting a catheter into the femoral artery, and electrocorticogram was also recorded. An expanding intracranial lesion was made by inflating the extradural balloon with physiological saline. The animals were arbitrarily divided into two groups.: 1) light or moderate groups which intracranial pressure before the injection of drug was below 400 mmH2O. 2) severe groups above 400 mmH2O. After the maintenance of the pressure, Solcoseryl was infused intravenously. The investigation was focused to observe whether Solcoseryl reveales any potent effect on cerebral blood flow, intracranial pressure, systemic blood pressure and on electroencephalogram in acute intracranial hypertension. Results 1) Intravenous injection of Solcoseryl had the effect of lowering intracranial pressure in the light or moderate and severe groups. Particularly, dose of 80 mg/kg showed the marked effect, though with a rebound phenomenon in the light or moderate groups. Furthermore, the effect was more marked and lasting by drip infusion of Solcoseryl and also by intravenous injection of Solcoseryl after pretreatment with hydrocortisone, and at this time no rebound phenomenon was recognized. 2) Solcoseryl had the effect of increasing the cerebral blood flow accompained with the lowering of intracranial pressure. 3) Systemic blood pressure was transiently lowered by the injection of Solcoseryl 20 mg/kg or 80 mg/kg and recovered immediately. 4) Solcoseryl had no effect on electroencephalogram in the severe groups. Conclusion On the basis of these results, it is rational to conclude that Solcoseryl could be superior agent render to lower intracranial pressure and to improve cerebral blood flow in acute intracranial hypertension.


Profunda Femoris Artery Perforator Propeller Flap: A Valid Method to Cover Complicated Ischiatic Pressure Sores.
We report the case of a 50-year-old paraplegic man with a complicated grade III/IV ischiatic pressure sore treated with a propeller flap based on the first perforator of the profunda femoris artery. Our aim was to surgically reconstruct an ischiatic pressure sore in a patient with ankylosis using a fasciocutaneous perforator propeller flap obtained from the posterior region of the thigh. Our decision to perform a profunda femoris artery perforator propeller flap reconstruction was mainly due to the anatomical contiguity of the flap with the site of the lesion and the good quality of the skin harvested from the posterior region of the thigh. The use of the perforator fasciocutaneous flap represents a muscle-sparing technique, providing a better long-term result in surgical reconstruction. The choice of the 180-degree propeller flap was due to its ability to provide a good repair of the pressure ulcer and to pass over the ischiatic prominence in the patient in the forced decubitus position. The operatory course did not present any kind of complication. Using this reconstructive treatment, we have obtained complete coverage of the ischiatic pressure sore.


Magnetic-Field Effect as a Tool to Investigate Electron Correlation in Strong-Field Ionization.
The influence of the magnetic component of the driving electromagnetic field is often neglected when investigating light-matter interaction. We show that the magnetic component of the light field plays an important role in nonsequential double ionization, which serves as a powerful tool to investigate electron correlation. We investigate the magnetic-field effects in double ionization of xenon atoms driven by near-infrared ultrashort femtosecond laser pulses and find that the mean forward shift of the electron momentum distribution in light-propagation direction agrees well with the classical prediction, where no under-barrier or recollisional nondipole enhancement is observed. By extending classical trajectory Monte Carlo simulations beyond the dipole approximation, we reveal that double ionization proceeds via recollision-induced doubly excited states, followed by subsequent sequential over-barrier field ionization of the two electrons. In agreement with this model, the binding energies do not lead to an additional nondipole forward shift of the electrons. Our findings provide a new method to study electron correlation by exploiting the effect of the magnetic component of the electromagnetic field.


How to Select an Extracellular Matrix for Wound Repair: A Comprehensive Review.
An extracellular matrix (ECM) is a network of proteins and other molecules that provide support and structure to cells and tissues in the body. Since its discovery in 1930, researchers have reproduced the ECM through an array of evolving technologies, developing products that accelerate healing times, minimize scarring, and reduce pain. When selecting which ECM product to use, physicians rely on personal experience while considering wound location, type of tissue lost, exposed structures, chronicity, and even the patient's religious preferences. While comparison trials between a few different types of ECMs exist, there lacks a thorough investigation that assesses a majority of ECMs against each other. Herein, we conducted a literature review using the PubMed database and utilized 71 articles to identify the best ECM for wound healing and positive patient outcomes. The primary search terms included extracellular matrix, xenograft, porcine, bovine, allograft, bioengineered matrix, acellularized fish skin, wounds, wound healing, and wound care. We did not exclude any specific type of research, but predominantly reviewed clinical trials, case series, and other review articles. We focused on the most popular and commonly used ECMs and constructed our results into the Table. We compared the indications, advantages, and disadvantages of each ECM and concisely illustrated these findings to provide a guide on how to select an ECM (Table). Allografts, whether they are glycerol or cryopreserved, suffice as a treatment choice and are superior to exposure healing. However, they do not produce healing at the same rate or quality as bioengineered matrices, porcine and bovine xenografts, or acellularized fish skin (AFS). Bioengineered matrices and porcine and bovine xenografts offer antimicrobial properties, low immunogenicity, cost effectiveness, and availability. The compromise with these ECMs is with healing times and cosmesis. Acellularized fish skin (AFS) provides diverse utility, antimicrobial activity, low immunogenicity, faster healing times, and cosmetic superiority. However, AFS yields a potential cost burden and is not plentiful or easily accessible in some parts of the world. Our findings assist in removing the subjectivity component of selecting an ECM and suggest further comparison or head-to-head trials would yield a more algorithmic approach to wound healing. We suggest to consider implementing the Disabilities of the Arm, Shoulder, and Hand (DASH) score as an additional objective comparison method in these future trials.


Old prospects in cardiovascular engineering.
For more than thirty years the thrombogenicity of blood-contacting materials has been deplored. This impotency, combined with inappropriate mechanical properties of these materials, explains the poor patency of medium-sized arterial prostheses and the lack of substitutes for small diameter arteries (psi<or=5 mm). The author here recalls several studies, among many others, which have opened opportunities to improve this situation. However there is a gap which has not been jumped over yet between laboratory experiments and the availability of devices which could be clinically tried. This step clearly needs strong investments from the industry people, and the latter should be encouraged to do so by the public health authorities, as far as they believe that innovation is the condition of therapeutic progress as well as social and economic benefits.


Altered expression of chondroitin sulfate structure modifying sulfotransferases in the articular cartilage from adult osteoarthritis and Kashin-Beck disease.
To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls. Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 - CHST-15, and uronyl 2-O-sulfotransferase - UST) were examined by immunohistochemical (IHC) staining and semi-quantitative analysis. Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage. The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment.


Influence of Duration of Injury on Diffusion Tensor Imaging in Acute Canine Spinal Cord Injury.
Diffusion tensor imaging (DTI) quantifies microstructural lesion characteristics, but impact of the interval between spinal cord injury (SCI) and examination on imaging characteristics is unclear. Our objective was to investigate the impact of duration of injury on DTI indices in dogs with acute, spontaneous SCI from thoracolumbar intervertebral disc herniation (IVDH) and explore associations with clinical severity. Twenty-six dogs with acute thoracolumbar IVDH of variable severity who underwent DTI were included. Neurological severity was graded using the modified Frankel Score (0-V). Fractional anisotropy (FA) and mean diffusivity (MD) were calculated on regions of interest within and adjacent to the lesion epicenter. Relationships between FA or MD and duration (injury to imaging interval) or neurological severity were determined using regression analysis and Wilcoxon rank sum. Median age was 6.8 years (1-13), median duration was 1.5 days (1-9), and neurological signs ranged from ambulatory paraparesis (MFS II) to paraplegia with absent pain perception (MFS V). Mean FA was 0.61 ± 0.09 cranial to the lesion, 0.57 ± 0.12 at the epicenter and 0.55 ± 0.10 caudally. Mean MD was 1.18 × 10-3 ± 0.0002 cranially, 1.09 × 10-3 ± 0.0002 at the epicenter, and 1.14 × 10-3 ± 0.0002 caudally. Accounting for neurological severity and age, FA caudal to the epicenter decreased with increasing duration of injury (p = 0.02). Lower MD within the lesion epicenter was associated with worse neurological severity (p = 0.01). Duration of injury should be considered when interpreting DTI results in dogs with acute thoracolumbar IVDH. The MD might differentiate injury severity in the acute setting and be worthy of development as an imaging biomarker.


Screening practices for obstructive sleep apnea in healthy community people: a Chinese community-based study.
Owing to the lack of clear guidelines, the significance of obstructive sleep apnea (OSA) screening in healthy community people is unclear. This study aimed to screen for OSA in a healthy community population and provide a basis for its screening. Permanent residents from five communities in the coastal and mountainous areas of south China were selected. The screening process included demographic and sleep questionnaire surveys, and an OSA screening. To compare the prevalence and risk factors of OSA in different areas, a type IV wearable intelligent sleep monitor (WISM) was used for screening. A total of 3,650 participants completed all studies, with a mean age of 53.81±12.71 years. In addition, 4,318 participants completed the OSA screening within 30 days, and the objective screening speed was 200 people per day. The recovery rate of the screening equipment was 99.37% (4,291/4,318), the screening success rate was 89.63% (3,846/4,291), and the rejection rate was 2.7% (120/4,438). The prevalence of high-risk OSA screened using the Stop-Bang questionnaire was 42.8% (1,563/3,650) and that screened using the device was 30.7% (1,119/3,650). The prevalence of OSA screened using the Stop-Bang questionnaire was higher than that screened using the device (P<0.01). Further analysis of sleep quality and daytime sleepiness showed that 47.6% (1,736/3,650) of the community population had good sleep quality and 6.6% (240/3,650) had daytime sleepiness. Age, sex, body mass index (BMI), neck circumference, and hypertension were risk factors for OSA in the community population. The use of objective type IV sleep detection equipment to screen a large sample population in the community in a short time is feasible. The prevalence of high-risk OSA screened using the Stop-Bang questionnaire was higher than that screened using the objective screening device.


Celebrating the 125th anniversary of the American Psychological Association: A quarter century of neuropsychology.
The American Psychological Association (APA) celebrated its 125th anniversary in 2017. As part of this celebration, the APA journal Neuropsychology has published in its November 2017 issue 11 papers describing some of the advances in the field of neuropsychology over the past 25 years. The papers address three broad topics: assessment and intervention, brain imaging, and theory and methods. The papers describe the rise of new assessment and intervention technologies, the impact of evidence for neuroplasticity on neurorehabilitation. Examples of the use of mathematical models of cognition to investigate latent neurobehavioral processes, the development of the field of neuropsychology in select international countries, the increasing sophistication of brain imaging methods, the recent evidence for localizationist and connectionist accounts of neurobehavioral functioning, the advances in neurobehavioral genomics, and descriptions of newly developed statistical models of longitudinal change. Together the papers convey evidence of the vibrant growth in the field of neuropsychology over the quarter century since APA's 100th anniversary in 1992. (PsycINFO Database Record


The diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin in the prediction of acute kidney injury in emergency department patients with suspected sepsis.
We assess the diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin (NGAL) to predict acute kidney injury in emergency department (ED) patients with suspected sepsis. We conducted a secondary analysis of a prospective observational study of a convenience sample of patients from 10 academic medical center EDs. Inclusion criteria were adult patients aged 18 years or older, with suspected infection or a serum lactate level greater than 2.5 mmol/L; 2 or more systemic inflammatory response syndrome criteria; and a subsequent serum creatinine level obtained within 12 to 72 hours of enrollment. Exclusion criteria were pregnancy, do-not-resuscitate status, cardiac arrest, or dialysis dependency. NGAL was measured in plasma collected at ED presentation. Acute kidney injury was defined as an increase in serum creatinine measurement of greater than 0.5 mg/dL during 72 hours. There were 661 patient enrolled, with 24 cases (3.6%) of acute kidney injury that developed within 72 hours after ED presentation. Median plasma NGAL levels were 134 ng/mL (interquartile range 57 to 277 ng/mL) in patients without acute kidney injury and 456 ng/mL (interquartile range 296 to 727 ng/mL) in patients with acute kidney injury. Plasma NGAL concentrations of greater than 150 ng/mL were 96% sensitive (95% confidence interval [CI] 79% to 100%) and 51% (95% CI 47% to 55%) specific for acute kidney injury. In comparison, to achieve equivalent sensitivity with initial serum creatinine level at ED presentation required a cutoff of 0.7 mg/dL and resulted in specificity of 17% (95% CI 14% to 20%). In this preliminary investigation, increased plasma NGAL concentrations measured on presentation to the ED in patients with suspected sepsis were associated with the development of acute kidney injury. Our findings support NGAL as a promising new biomarker for acute kidney injury; however, further research is warranted.


Innovative antimicrobial susceptibility testing method using surface plasmon resonance.
Utilizing the ultra sensitivity of surface plasmon resonance (SPR) biosensor to examine drug resistance of bacteria was studied in this research. Susceptible and resistant strains of Escherichia coli JM109 to ampicillin and those of Staphylococcus epidermidis to tetracycline, served as a blind test, were examined. The bacteria adhered on the Au thin film was treated by the injection of antibiotic flow. The optical property change of the bacteria responded to antibiotics were recorded through SPR mechanism. As a result, the susceptible strain of E. coli generally revealed more than three times of SPR angle shift when compared to the resistant one; the susceptible strain of S. epidermidis revealed irregular SPR angle shift while the resistant strain kept the SPR angle almost unchanged. The new SPR method took less than 2h of antibiotic treatment time to complete the antimicrobial susceptibility test. Different from conventional applications of SPR, specific antibodies is not required in this method. As compared to the conventional assays, Kirby-Bauer disk diffusion and variations of broth microdilution usually take 1 day to weeks to issue the report. Using this SPR assay can greatly reduce the waiting period for laboratory tests, and can therefore benefit patients who need proper antibiotic treatments to control bacterial infections. The sensitivity of the SPR biosensor built for the application is around 1.4 x 10(-4) on the refractive index.


[Intestinal metastases from breast cancer. Apropos of 8 cases].
Eight patients with intestinal metastases from breast cancer are described. The different clinical presentations and pathological types are studied. The difficulty in distinguishing such uncommon secondary sites of breast cancer from primary intestinal cancer is emphasized. Attention should be paid to intestinal symptoms in women with a history of infiltrating lobular breast cancer: in agreement with recent literature data the lobular type seems mainly responsible for gastrointestinal and peritoneal involvement originating from breast cancer (7 cases out of 8 in our series). Prolonged survival could be obtained if no metastases elsewhere were found with appropriate treatment including ablative surgery, chemotherapy and hormonotherapy.


From home to hospital: Parallels in birthing and dying in twentieth-century Canada.
This article highlights the striking parallels in the history of birthing and dying as they moved from home to hospital in Canada in the twentieth century. It shows that deaths, like birth, has been hidden in hospitals only since mid-century. It demonstrates that the availability of paid and unpaid female caregivers was a key factor affecting the shifts in location of death, much as it was for birth. Thus, women have been the major consumers and caregivers of health services at both ends of the life cycle.


Assessment of Photoreleasable Linkers and Light-Capturing Antennas on a Photoresponsive Cobalamin Scaffold.
Cobalamin has shown promise as a light-sensitive drug delivery platform owing to its ease of modification and the high quantum yields for drug photorelease. However, studies to date on the general photochemistry of alkyl cobalamins have primarily focused on methyl and adenosyl-substituted derivatives, the natural cofactors present in various enzymatic species. We describe the synthesis and photolytic behavior of cobalamin conjugates comprised of different combinations of fluorophores and β-axial ligands. In general, cobalamin conjugates containing β-axial alkyl substituents undergo efficient photolysis under aqueous conditions, with quantum yields up to >40%. However, substituents that are large and hydrophobic, or unable to readily support the presumed radical intermediate, suffer less efficient photolysis (<15%) than smaller, water-soluble, analogs. By contrast, quantum yields improve by 2-fold in DMF for cobalamins containing large hydrophobic β-axial substituents. This suggests that drug release from carriers comprised of membranous compartments, such as liposomes, may be significantly more efficient than the corresponding photorelease in an aqueous environment. Finally, we explored the impact of fluorophores on the photolysis of alkyl cobalamins under tissue-mimetic conditions. Cobalamins substituted with efficient photon-capturing fluorophores display up to 4-fold enhancements in photolysis relative to unsubstituted derivatives. In summary, we have shown that the photosensitivity of alkyl cobalamin conjugates can be tuned by altering the Co-appended alkyl moiety, modulating the polarity of the environment (solvent), and installing photon-capturing fluorophores onto the cobalamin framework.


Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.
Type 2 diabetes mellitus (T2DM) is a complex disease that involves a wide range of genetic and environmental factors. The hepatocyte nuclear factor (HNF4A) carries out hepatic gluconeogenesis regulation and insulin secretion crucially, and the corresponding gene was shown to be linked to T2DM in several studies. The aim of the present study was to evaluate the association between HNF4A genetic variants (rs1884613 and rs1884614) and T2DM risk in a group of Iranian patients. This case-control study included 100 patients with T2DM and 100 control subjects. Genotyping of two single nucleotide polymorphisms (SNPs) (rs1884613 and rs1884614) of HNF4A was performed using the sequencing method. There was no statistically significant difference for allele and genotype distribution of the HNF4A common variants (rs1884613 and rs1884614) between subjects with and without T2DM (P=0.9 and P=0.9, respectively). Regarding diabetic complications, although the presence of mentioned polymorphisms increased the odds of developing ophthalmic complications and reduction of the odds of renal complications among diabetic patients, the mentioned risk was non- significant and cannot be generalized to the whole population. It seems that rs1884613 and rs1884614 polymorphisms are not associated with T2DM or its renal and ophthalmic complications. To investigate the precise influence of these polymorphisms, prospective cohorts with larger sample sizes are required.


Intensive care research coordinators: who are they and what do they do? Results of a binational survey.
Research coordinators in intensive care are a growing specialty about which little is known. This cross-sectional study surveyed the Australia and New Zealand Intensive Care Research Coordinators' Group (n = 49) regarding demographics, education, employment history, job structure, and role content. Most research coordinators were highly qualified and experienced nurses who undertake pharmaceutical trials, multicenter projects, departmental medical and nursing research, audits and data registries, and their own projects.


Dietary patterns and health-related quality of life among Iranian adolescents.
Examining the associations of a-posteriori-defined dietary patterns and health-related quality of life (HRQOL) among Iranian adolescents. This cross-sectional study was conducted among 900 apparently healthy students (mean age 15.33 years; 53.0% female) during 2020-21. The validated Persian version of self-report Pediatric Quality of Life Inventory™ Version 4.0 Generic Core Scales (PedsQL) for healthy adolescents was used in an online survey to assess HRQOL. Total, physical health, psychosocial health, emotional functioning, social functioning, and school functioning PedsQL scores were calculated, and impaired HRQOL was defined as > 1 standard deviation below the total population sample mean PedsQL scores. A validated food frequency questionnaire was used to assess dietary intakes during telephone interviews. Daily intakes of 20 predefined food groups were calculated and submitted to the principal component factor analysis to identify a-posteriori-defined dietary patterns. Three major dietary patterns labeled as Mediterranean, mixed, and unhealthy were identified, of which only the Mediterranean pattern characterized by high intakes of vegetables, fruits, olives, potatoes, eggs, nuts and legumes, pickles, low-fat dairy, fish, poultry, and vegetable oils was consistently associated with HRQOL. Controlling for covariates in the multivariable-adjusted binary logistic regression analysis, participants in the top tertile of Mediterranean pattern score were less likely to have impaired HRQOL than those in the bottom tertile (total: OR 0.25; physical health: OR 0.35; psychosocial health: OR 0.15; emotional functioning: OR 0.17; social functioning: OR 0.15; and school functioning: OR 0.18; all P < 0.010). Current findings indicate that an a-posteriori-defined Mediterranean-style dietary pattern is associated with better HRQOL among healthy Iranian adolescents.


Gas-phase ion chemistry of the allene-phosphine and silane-allene-phosphine systems.
The gas-phase ion chemistry of allene-phosphine and silane-allene-phosphine mixtures was studied by ion trap mass spectrometry. Rate constants of the main processes were measured and compared with the collisional rate constants to determine the reaction efficiencies. For the binary mixture, the highest yield of C- and P-containing ions is obtained with a 1 : 1 partial pressure ratio among the reagents. In the ternary mixture, formation of ion species containing Si, C and P together is mainly achieved in reactions of Si/P ions with allene, with a lower contribution from reactions of Si/C and C/P ions with phosphine and silane, respectively. The formation of ternary ion clusters is related to their possible role as precursors of amorphous silicon carbides doped with phosphorus, obtained by deposition from properly activated silane-allene-phosphine mixtures.


Immunotherapy for the treatment of multiple myeloma.
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade. Genetically engineered T cells, such as chimeric antigen receptor T cells or T cell receptor-engineered T cells, have also shown encouraging results in recent clinical studies of patients with MM. In this paper, we discuss recent progress in immunotherapy for the treatment of MM.


The composition of alcohol products from markets in Lithuania and Hungary, and potential health consequences: a pilot study.
The rates of alcohol-attributable mortality in Lithuania and Hungary have been shown to be higher than those in most other European countries. Quality of alcohol products is investigated as a possible explanation. In a descriptive pilot study, a convenience sample of alcohol products was collected from local city markets in both countries (Lithuania n = 10, Hungary n = 15) and chemical analyses, including some that have not been done in prior studies, were conducted. The parameters studied were alcoholic strength, volatiles (methanol, acetaldehyde, higher alcohols), ethyl carbamate, anions (including nitrate) and inorganic elements (including lead). Additionally, a multi-target screening analysis for toxicologically relevant substances was conducted. The majority of samples (64%) had an alcohol content between 35% vol. and 40% vol., being in accordance with the typical strength of legal spirits in Europe. Three samples containing significantly higher concentrations of alcohol above 60% vol. were found to be unrecorded alcohol products, defined as any alcohol that is outside of legal and taxed production. Screening analysis showed that those samples contained various flavourings, including the hepatotoxic substance coumarin, at concentrations above the legal limit for foods. All other substance classes under study were found to be at levels of no toxicological concern. Although some problems with the quality of the alcohol samples were found, there is insufficient evidence from this pilot study to conclude that alcohol quality has an influence on health as reflected in alcohol-attributable mortality rates. Given the extent of alcohol-attributable disease burden in central and eastern European countries, future research should focus on collection of large, representative samples, particularly of unrecorded sources, which was the most problematic product group in our study.


Mucosal immune system of the gastrointestinal tract: maintaining balance between the good and the bad.
The gastrointestinal tract (GI tract) is a unique organ inhabited by a range of commensal microbes, while also being exposed to an overwhelming load of antigens in the form of dietary antigens on a daily basis. The GI tract has dual roles in the body, in that it performs digestion and uptake of nutrients while also carrying out the complex and important task of maintaining immune homeostasis, i.e., keeping the balance between the good and the bad. It is equally important that we protect ourselves from reacting against the good, meaning that we stay tolerant to harmless food, commensal bacteria and self-antigens, as well as react with force against the bad, meaning induction of immune responses against harmful microorganisms. This complex task is achieved through the presence of a highly efficient mucosal barrier and a specialized multifaceted immune system, made up of a large population of scattered immune cells and organized lymphoid tissues termed the gut-associated lymphoid tissue (GALT). This review provides an overview of the primary components of the human mucosal immune system and how the immune responses in the GI tract are coordinated and induced.


[Molecular dynamics simulation of force-regulated interaction between talin and Rap1b].
The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.


[Stimulation of respiration with Piladox in experimental and clinical conditions during administration of drugs for general anesthesia].
Experimental and clinical studies of the agent Piladox (RGH 2202) were conducted. Experiments on animals (rats, rabbits, mice) demonstrated that Piladox possesses the property of restoring respiration inhibited by narcotic analgesics and some general anesthetics as well as the respiratory-de-priming effect of acute blood loss and is a more effective stimulator of the respiratory center than cordiamine (nikethamide) or corasol. Clinical study of Piladox in 75 patients showed that intravenous infusion of 1 mg/kg of the agent in the awakening period produced a stimulating effect on respiration through increase of its frequency and increase of the respiratory volume. The minute respiratory volume in this case was even greater than the initial values, whereas the CO2 content in the blood and expired air reached the initial level. The hemodynamic values in this period remained generally stable. Piladox does not change the antinociceptive effect of the narcotic analgesics and analgesia in the immediate postoperative period when combined general anesthesia is applied.


Ultrastructural and microprobe analysis of simian lung mite pigments.
Using light microscopy, polarizable amorphorous bodies with tinctorial characteristics of lipochromes and flocculent pigmental materials were found within the alveolar macrophages and peribronchiolar region of the lungs in a pig-tailed macaque (Macaca nemistrina) infected with simian lung mite (Pneumonyssus simicola). Examination of these pigmental bodies, using a high-voltage (1.2 meV) electron microscope and an energy-dispersive X-ray analysis system, indicated that the pigmental bodies contained a high concentration of silica. One female adult P simicola also was examined, and its digestive tract had visible, polarizable pigment and a high concentration of silica. Thus, lesions associated with lung mite infection in Old World monkeys may be superimposed by this silicotic condition, which may be associated with their arid, dusty, environment. Therefore, until the link between lung mite infection and silicosis is clarified, experimental inhalation toxicologic findings in mite-infected Old World monkeys should be interpreted cautiously.


Successful but limited use of external cephalic version in Auckland.
External cephalic version (ECV) can effectively reduce the chance of non-cephalic presentation at birth and reduce caesarean section rate for breech presentation at term. It is recommended in New Zealand to offer ECV to all eligible women with breech presentation at term. This study aims to determine the ECV success rate at our hospital, factors that predict ECV success, and perinatal outcomes for women who had ECV, and to estimate the ECV attempt rate at our hospital. A prospective audit was performed of all women with singleton non-cephalic presentation>or=36 weeks who attended the ECV clinic at National Women's Health in Auckland from July 2002 to January 2006. Two hundred and fifty five women presented for ECV during the study period, and the ECV success rate was 59%. The strongest predictor of ECV success was an unengaged presenting part. Women with successful ECV had a vaginal birth rate of 67%. Three women needed to have an ECV attempt in order to prevent one caesarean section. We estimated that 26% of women with term breech presentation had an ECV attempt. ECV at National Women's Health is effective at reducing beech presentation at term and at restoring a caesarean section rate equivalent to that of cephalic singleton pregnancy at term. However, the low rate of referral should be addressed.


Use of Simvastatin and Risk of Acute Pancreatitis: A Nationwide Case-Control Study in Taiwan.
The correlation between simvastatin use and acute pancreatitis is explored. A case-control study was conducted to analyze claim data from the Taiwan National Health Insurance Program. The case group comprising a total of 3882 subjects aged 20 to 84 years with their first acute pancreatitis episode occurring between 1998 and 2011 formed the case group, against 3790 randomly selected controls matched for sex, age, comorbidities, and index year of acute pancreatitis diagnosis. Recent use of simvastatin was defined as subjects whose last remaining simvastatin tablet was noted ≤7 days before the date of acute pancreatitis diagnosis. Remote use of simvastatin was defined as subjects whose last remaining 1 tablet for simvastatin was noted >7 days before the date of acute pancreatitis diagnosis. Never use of simvastatin was defined as subjects who had never been prescribed simvastatin. A multivariable unconditional logistic regression model was used to estimate the odds ratio and 95%CI to explore the correlation between simvastatin use and acute pancreatitis. After adjustment for confounders, multivariable logistic regression analysis revealed that the adjusted odds ratio of acute pancreatitis was 1.3 for subjects with recent use of simvastatin (95%CI 1.02, 1.73), when compared with those with never use of simvastatin. The crude odds ratio decreased to 1.1 for those with remote use of simvastatin (95%CI 0.93, 1.34) but without statistical significance. Recent use of simvastatin is associated with acute pancreatitis. Clinicians should consider the possibility of simvastatin-associated acute pancreatitis for patients presenting for acute pancreatitis without known cause.