APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition.
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and APOBEC3B have emerged as key mutation drivers in cancer. Here, we show that APOBEC3A and APOBEC3B activities impose a unique type of replication stress by inducing abasic sites at replication forks. In contrast to cells under other types of replication stress, APOBEC3A-expressing cells were selectively sensitive to ATR inhibitors (ATRi), but not to a variety of DNA replication inhibitors and DNA-damaging drugs. In proliferating cells, APOBEC3A modestly elicited ATR but not ATM. ATR inhibition in APOBEC3A-expressing cells resulted in a surge of abasic sites at replication forks, revealing an ATR-mediated negative feedback loop during replication. The surge of abasic sites upon ATR inhibition associated with increased accumulation of single-stranded DNA, a substrate of APOBEC3A, triggering an APOBEC3A-driven feed-forward loop that ultimately drove cells into replication catastrophe. In a panel of cancer cell lines, ATRi selectively induced replication catastrophe in those harboring high APOBEC3A and/or APOBEC3B activities, showing that APOBEC3A and APOBEC3B activities conferred susceptibility to ATRi. Our results define an APOBEC-driven replication stress in cancer cells that may offer an opportunity for ATR-targeted therapy. Cancer Res; 77(17); 4567-78. ©2017 AACR.


Cyclin/cdk2 complexes in the nucleus of HeLa cells.
Two different fractions of cdk2 and cdc2 have been found in the nucleus of HeLa cells. One, which can be extracted by nuclease treatment, possibly associated with DNA- or RNA-containing structures and another one, which is bound to the nuclear matrix. Nuclear cdk2 forms high molecular weight complexes which migrate at the same position as DNA polymerase alpha and proliferating cell nuclear antigen in sucrose gradient centrifugation experiments. These results suggest that nuclear cdk2 complexes could be associated with the replication factories. Immunoprecipitation experiments reveal that nuclear cdk2 complexes display histone H1-kinase activity and phosphorylate a protein of 18 kDa which is present in these complexes.


Systematic identification of interaction effects between genome- and environment-wide associations in type 2 diabetes mellitus.
Diseases such as type 2 diabetes (T2D) result from environmental and genetic factors, and risk varies considerably in the population. T2D-related genetic loci discovered to date explain only a small portion of the T2D heritability. Some heritability may be due to gene-environment interactions. However, documenting these interactions has been difficult due to low availability of concurrent genetic and environmental measures, selection bias, and challenges in controlling for multiple hypothesis testing. Through genome-wide association studies (GWAS), investigators have identified over 90 single nucleotide polymorphisms (SNPs) associated to T2D. Using a method analogous to GWAS [environment-wide association study (EWAS)], we found five environmental factors associated with the disease. By focusing on risk factors that emerge from GWAS and EWAS, it is possible to overcome difficulties in uncovering gene-environment interactions. Using data from the National Health and Nutrition Examination Survey (NHANES), we screened 18 SNPs and 5 serum-based environmental factors for interaction in association to T2D. We controlled for multiple hypotheses using false discovery rate (FDR) and Bonferroni correction and found four interactions with FDR <20 %. The interaction between rs13266634 (SLC30A8) and trans-β-carotene withstood Bonferroni correction (corrected p = 0.006, FDR <1.5 %). The per-risk-allele effect sizes in subjects with low levels of trans-β-carotene were 40 % greater than the marginal effect size [odds ratio (OR) 1.8, 95 % CI 1.3-2.6]. We hypothesize that impaired function driven by rs13266634 increases T2D risk when combined with serum levels of nutrients. Unbiased consideration of environmental and genetic factors may help identify larger and more relevant effect sizes for disease associations.


[Late presentation of congenital diaphragmatic hernia].
Congenital diaphragmatic hernia (CDH) is a rare congenital defect. Most cases are currently diagnosed either prenatally by ultrasound or shortly after birth. Late presentation of CDH is uncommon, and symptoms vary greatly. Here we describe two cases. The first concerns a 9-year-old boy with abdominal pain. The symptoms were interpreted as constipation and he was admitted for a high enema. After a few hours he developed severe respiratory distress; chest X-ray revealed a tension gastrothorax, and thoracostomy resulted in immediate respiratory improvement. In the second case, a 6-month-old girl presented with haematemesis and electrolyte imbalance. She was admitted for rehydration and correction of the electrolyte balance. A chest X-ray was performed because of persistent vomiting, and this showed an intrathoracal stomach. Late presentation of CDH is often misdiagnosed, with the risk of serious morbidity and mortality. Tension gastrothorax is a rare, life-threatening complication which should be treated by emergency gastric decompression..


A stereological analysis of the response of spermatogenesis to an acute inflammatory episode in adult rats.
Male fertility is inhibited by inflammatory disease, but the mechanisms responsible are poorly defined. The effects of acute systemic inflammation induced by a single IP injection of lipopolysaccharide (LPS) on spermatogenic function in adult male rats were investigated using detailed stereological analysis. The earliest effect observed was a significant maturational delay of meiosis during the leptotene/zygotene phase (at stages IX-XIII) within 24 hours. This was followed within 6 days by an increase in premature release of these cells and the adjacent, more luminally located generation of round spermatids from the seminiferous epithelium. An increase in germ cell apoptosis within stages IX-XIII also occurred at this time. These data indicate that the initial effects of acute inflammation on the seminiferous epithelium are most pronounced on stages IX-XIII. The effects were not consistent with a loss of hormonal regulation, suggesting that a direct effect of inflammation on the function of the Sertoli cell during this critical stage of meiosis is involved. In the longer term, however, the consequences of this acute inflammatory episode were relatively minor: within 28 days there had been a compensatory increase in the efficiency of the seminiferous epithelium, restoring the spermatogenic capacity of the testis towards preinflammation levels.


Calcitonin-producing insulinoma. An immunohistochemical and electron microscopic study.
A pancreatic endocrine tumor measuring 1.5 X 1.0 X 1.0 cm in a 67-year-old man with recurrent hypoglycemic attacks was examined by immunohistochemistry and electron microscopy. The tumor cells were relatively uniform, and almost all of them were immunoreactive to insulin. A few calcitonin-positive cells could be identified scattering in tumor cell strands, and the content of calcitonin in the tumor was 85 ng/g wet tissue. Coexistence of insulin and calcitonin in tumor cells was demonstrated by using adjacent semithin sections of the Epon-embedded material. Electron microscopically, the tumor consisted of a single type of cells with secretory granules identical to B-cell granules in the normal counterpart.


Age at menarche and prevalence of oligo/amenorrhea in top Polish athletes.
The representative sample of a population of top Polish athletes (>75% of all participants in Poland's Winter and Summer National Championships during 1992-1994) was investigated using a questionnaire. The athletic group numbered 926 women in total. The control group (n = 708) in the same age range (15-37 years) as the athletes was randomly chosen from the Warsaw population. The mean menarcheal age of all athletes was 13.6 ± 1.3 years, and it was statistically different from the controls (12.9 ± 1.2 years). Athletes who started training before menarche were more numerous (661) than those who started training after menarche (265). The mean menarcheal age was also different for those groups (13.9 ± 1.3 years vs. 13.0 ± 1.3 years). In all sports except cross-country skiing and biathlon, the menarcheal age of girls starting training before menarche was later as compared to the age of those starting training after menarche. The prevalence of oligo/amenorrhea (⩽9 menstrual cycles per year) was much higher for all younger and premenarche trained athletes than postmenarche trained girls. This prevalence also was much higher for athletes than for controls. Early maturers were engaged in team games, fencing, and judo, but late maturers were engaged in cross-country skiing and biathlon, track and field-long and middle distances, and marathon. It may indicate the presence of the sport's selection factor. Am. J. Hum. Biol. 10:511-517, 1998. © 1998 Wiley-Liss, Inc.


In vitro anti-aging activities of extracts from leaves of Ma Kiang (Cleistocalyx nervosum var. paniala).
Cleistocalyx nervosum (DC.) Kosterm. var. paniala (Roxb.) J. Parn. & Chantaran. (Myrtaceae) or Ma Kiang contains high amounts of phenolic compounds. Antioxidant activity of its fruit and seed has been investigated. However, limited available information concerning the biological activities of its leaves has been reported. To investigate the in vitro anti-aging potential of young and old leaves of Ma Kiang. Ma Kiang leaves were extracted using water, methanol, and chloroform as the solvents by cold (sonication) and hot (boiling) processes. The extracts were determined for total phenolic and flavonoid contents. The extracts (at 0.001-10 mg/ml) were tested for antioxidative and tyrosinase inhibition activities using a colorimetric method. The cytotoxicity of extracts (at 0.0001-1 mg/ml) was determined with human skin fibroblasts. Also, the extracts at 0.001, 0.01, and 0.1 mg/ml which showed no toxicity were tested for MMP-2 inhibition. The cold methanol extract of the old leaves showed the highest total phenolic and flavonoid contents of 511.44 ± 18.23 μg GAE/mg and 262.96 ± 2.98 μg QE/mg, respectively. This extract also gave high free radical scavenging, lipid peroxidation inhibition, and tyrosinase inhibition activities with SC50, IPC50, and IC50 values of 0.02 ± 0.004, 0.23 ± 0.13, and 0.02 ± 0.006 mg/ml, respectively. The extract at 0.1 mg/ml exhibited the highest MMP-2 inhibition of 91.14 ± 1.67%. The anti-aging potential of the cold methanol extract from old leaves of Ma Kiang can be further developed as an anti-aging agent.


Diaquabis[2'-(4,5-diazafluoren-9-ylidene)picolinohydrazidato-kappa2N,O]zinc(II) tetrahydrate: a metal-water chain complex containing cyclic water hexamers.
In the title compound, [Zn(C17H10N5O)2(H2O)2].4H2O, cyclic water hexamers forming one-dimensional metal-water chains are observed. The water clusters are trapped by the co-operative association of coordination interactions and hydrogen bonds. The ZnII ion resides on a centre of symmetry and is in an octahedral coordination environment comprising two O atoms and two N atoms from two 2'-(4,5-diazafluoren-9-ylidene)picolinohydrazidate ligands and two water molecules.


Critical health psychology Critical health psychology Michael Murray Palgrave No of pages: 270 £17.99 033399034X 033399034X [Formula: see text].
This edited book provides a very useful introduction to contemporary ideas in health psychology theory and practice. 'Critical' is a term with many meanings. For this book the writers use it to mean a theoretically informed practice in the wake of Foucault's analysis of power.


Clarification of the "pain neuroscience education" concept in the management of patients with persistent low back pain: A scoping review.
Patient education is a recommended treatment strategy for persistent low back pain (PLBP). Pain neuroscience education (PNE) is an emerging concept with boundaries still unclear. To clarify the PNE concept and identify its key characteristics in PLBP management. A systematic search was conducted using the following databases: Pubmed, ScienceDirect, Google Scholar, Cochrane, and Pedro. publications in English or French on pain neuroscience education and chronic low back pain, educational books cited in white literature. Three reviewers independently selected eligible studies for final inclusion. Numerical analysis and narrative synthesis were carried out from the extracted data. From 919 identified publications, 54 were selected. Ten educational resources were added. PNE refers to a theoretical framework, a specific educational intervention, and an overall care approach. It is characterized by the intention to help the patient reconceptualize their PLBP from a tissue injury marker to a protective, neurobiological perspective, and then to increase adherence to biopsychosocial rehabilitation and normalize cognitive-behavioral responses. Pain sciences concepts are presented with an optimization of learning strategies. PNE stands out from other educational and cognitive behavioral approaches through its objective of changing the pain concept.


Menorrhagia due to a qualitative deficiency of plasminogen activator inhibitor-1: case report and literature review.
A case is presented of a 26-year-old woman who was referred to the hematology clinic because of her report of a family history of plasminogen activator inhibitor-1 (PAI-1) deficiency. Since menarche, she had suffered from severe menorrhagia, but she had assumed that this was unrelated to her mother's history of repeated life-threatening bleeding. Her menorraghia was evident by using greater than 100 pads per period, bleeding as long as 4 continuous months, and even bleeding through her clothes despite using both tampons and pads. Evaluation with pelvic examination, endometrial biopsy, and pelvic ultrasound was unremarkable. Medroxyprogesterone acetate treatment for her dysfunctional uterine bleeding was unsuccessful. Laboratory evaluation revealed iron deficiency anemia but otherwise normal platelets, bleeding time, prothrombin time, activated partial thromboplastin time, and vonWillebrand's studies. Despite any preconceptions, examination for a fibrinolytic defect ultimately demonstrated a PAI-1 antigen level of 11.4 ng/mL (4.0-43 ng/mL) and PAI-1 activity less than 5 AU/mL (5-37 AU/mL) and clinically supported a diagnosis of a hereditary, qualitative PAI-1 defect. She was treated with aminocaproic acid with return to relatively normal menses. Future treatment should also prevent excessive bleeding during trauma, surgery, or childbirth. Further evaluation of this patient and her family is planned and may help elucidate the important role of PAI-1 in the complicated balance between hemostasis and hemorrhage.


Surgical management of patients with ulcerative colitis during pregnancy: maternal and fetal outcomes.
Ulcerative colitis can develop during the reproductive years, and there are limited data about perinatal care for patients with ulcerative colitis. In this study, we analyzed perinatal follow-up, complications, and maternal and fetal outcomes in pregnant patients undergoing surgery for ulcerative colitis. Between January 1998 and July 2013, female patients who underwent surgery during pregnancy for abdominal complications of ulcerative colitis and followed up during their pregnancy in our institution were included in our study. Patient characteristics, complications, operations performed, maternal and fetal morbidity and mortality during the perinatal period, and type of delivery were analyzed. There were nine female patients with a median (range) age of 30 (21-33) years. Indications for surgery were fulminant/refractory colitis (n = 6) and bowel obstruction (n = 3). Operations performed were subtotal colectomy with an end ileostomy (n = 3), Turnbull blowhole procedure (n = 3), adhesiolysis with small bowel resection (n = 1), detorsion and decompression of bowel (n = 1) and adhesolysis (n = 1). Median (range) postoperative length of stay was 11 (5-28) days and median (range) duration of pregnancy was 36 (32-40) weeks. There were only two patients who had a transvaginal delivery, while a cesarean section was performed in seven patients. Indications for cesarean section were as follows: physician's preference (n = 4), planned small bowel surgery with cesarean section (n = 2), and metabolic disorders (n = 1). There were no perinatal maternal or fetal deaths. Surgery for ulcerative colitis complications can be performed safely if indicated during pregnancy under the care of a multidisciplinary team that includes gastroenterologists, obstetricians, and colorectal surgeons.


A supraclavicular cystic lymphangioma in adult: a rare entity.
Cystic lymphangioma is a benign congenital disease that is more seen in head and neck regions. We report a case of a 54-year-old man with a growing supraclavicular mass. The ultrasonography and magnetic resonance imaging suggested a cystic lymphangioma. The mass was surgically totally removed without any recurrence. Histology examination confirmed the diagnosis. Cystic lymphangioma in adults is a rare entity and the literature on the subject is poor with no global recommendations.


Pulmonary Flow as an Improved Method for Determining Cardiac Output in Mice after Myocardial Infarction.
Echocardiography is a valuable noninvasive technique to estimate cardiac output (CO) from the left ventricle (LV) not only in clinical practice but also in small-animal experiments. CO is used to grade cardiac function and is especially important when investigating cardiac injury (e.g., myocardial infarction [MI]). Critically, MI deforms the LV, invalidating the assumptions fundamental to calculating of cardiac volumes directly from the LV. Thus, the purpose of this study was to determine if Doppler-derived blood flow through the pulmonary trunk (pulmonary flow [PF]) was an improved method over conventional LV-dependent echocardiography to accurately determine CO after MI. Variations in CO were induced either by transverse aortic constriction or MI. Echocardiography was performed in healthy (n = 27), transverse aortic constriction (n = 25), and MI (n = 41) mice. CO calculated from PF (pulsed-wave Doppler) was internally compared with CO calculated from left ventricular images using M-mode (Teichholz formula) and the single-plane ellipsoid two-dimensional (2D) formula and externally compared with the gold standard, flow probe CO. In healthy mice, all three echocardiographic methods (M-mode, 2D, and PF) correlated well with flow probe-derived CO. In MI mice, only PF CO values correlated well with flow probe values. Bland-Altman analysis confirmed that PF was improved over M-mode and 2D echocardiography. Inter- and intrauser variability of PF CO was reduced, and both inter- and intraclass correlation coefficients were improved compared with either M-mode or 2D CO calculations. PF CO calculated from pulsed-wave Doppler through the pulmonary trunk was an improved method of estimating CO over LV-dependent formulas after MI.


High accuracy of Karplus equations for relating three-bond J couplings to protein backbone torsion angles.
(3) JC'C' and (3) JHNHα couplings are related to the intervening backbone torsion angle ${\varphi }$ by standard Karplus equations. Although these couplings are known to be affected by parameters other than ${\varphi }$, including H-bonding, valence angles and residue type, experimental results and quantum calculations indicate that the impact of these latter parameters is typically very small. The solution NMR structure of protein GB3, newly refined by using extensive sets of residual dipolar couplings, yields 50-60 % better Karplus equation agreement between ${\varphi }$ angles and experimental (3) JC'C' and (3) JHNHα values than does the high-resolution X-ray structure. In intrinsically disordered proteins, (3) JC'C' and (3) JHNHα couplings can be measured at even higher accuracy, and the impact of factors other than the intervening torsion angle on (3) J will be smaller than in folded proteins, making these couplings exceptionally valuable reporters on the ensemble of ${\varphi }$ angles sampled by each residue.


Reducing interpersonal stress in dental practice.
Inherent in the dental situation is the potential for a great deal of interpersonal stress. While the particular areas of stressful interaction are as numerous and varied as are the approaches to deal with such situations, what may be of ultimate importance is what an individual tells himself or herself about such situations. Stresses become distressful when we interpret them as terrible, unfair, or catastrophic, rather than an unfortunate or undersirable, perhaps the inevitable result of the general nature of the human condition. We may not have the power or ability to control many external stress-producing events, but we do indeed have the ability to alter how we feel about such events by becoming aware of our self-defeating beliefs and negative self-talk, and subsequently by finding more appropriate and positive messages to tell ourselves about such occurrences. In addition, the quality of the emotional environment established in the dental office can be altered to reduce the interpersonal stresses resulting from poor communication between dentist, staff, and patient. The end result will hopefully be a longer and happier relationship for all persons involved in dentistry and better realization of everyone's stated goal-improved dental health.


Synthesis, characterization, and electrochemical relationships of dinuclear complexes of platinum(II) and platinum(III) containing ortho-metalated tertiary arsine ligands.
Reaction of 2-Li-4-MeC6H3AsPh2 with [PtCl2(SEt2)2] gives two isomeric dinuclear platinum(II) complexes, one containing a half-lantern structure with two chelating and two bridging C6H3-5-Me-2-AsPh2 ligands, [Pt2(kappa2As,C-C6H3-5-Me-2-AsPh2)2(mu-kappaAs,kappaC-C6H3-5-Me-2-AsPh2)2], and the other, a full-lantern with four bridging C6H3-5-Me-2-AsPh2 ligands, [Pt2(mu-kappaAs,kappaC-C6H3-5-Me-2-AsPh2)4]. The lantern structure of the latter is retained in the dihalodiplatinum(III) complexes that are formed by oxidative addition of chlorine, bromine, or iodine to the isomeric mixture. The dichloro derivative undergoes metathesis reactions with silver or sodium salts, yielding the corresponding cyano, thiocyanato, cyanato, and fluoro species. The structures of all complexes have been determined by single-crystal X-ray analysis. The oxidative addition products have Pt-Pt distances in the range 2.65-2.79 A (cf. 2.89 A in the lantern diplatinum(II) structure), consistent with the presence of a Pt-Pt bond. Electrochemical data lead to the conclusion that an initial rapid one-electron process and subsequent chemical reactions produce the dihalodiplatinum(III) lantern structure when mixtures of the lantern and half-lantern complexes are oxidized by halogens. The electrochemical data also explain why chemical reduction of the dihalodiplatinum(III) complex produces only the lantern diplatinum(II) complex.


Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured by thrombin generation time.
Patients with renal dysfunction who undergo systemic anticoagulation with enoxaparin are at increased risk for bleeding. Although there is decreased renal clearance of enoxaparin in this population, the clinical utility of monitoring antifactor Xa activity is controversial because it is weakly correlated to bleeding. The goal of this study was to investigate the role of other novel anticoagulation markers, such as thrombin generation time, platelet contractile force, and clot elastic modulus, while controlling for antifactor Xa activity in patients with and without renal dysfunction. Thirty anticoagulant- and antiplatelet-naive subjects completed this trial (10 controls, 10 patients with chronic kidney disease, and 10 patients with end-stage renal disease [ESRD]). Blood samples were obtained and spiked ex vivo with increasing concentrations of enoxaparin antifactor Xa activity (0.25, 0.5, 1.0, and 3.0 IU/mL). Thrombin generation time, platelet contractile force, and clot elastic modulus were measured in each group at each antifactor Xa activity concentration. Subjects with ESRD had an approximately 50% greater anticoagulant effect, determined by thrombin generation time prolongation, than controls at antifactor Xa activity concentrations of 0.5 to 3.0 IU/mL. This may explain why subjects with ESRD with seemingly therapeutic antifactor Xa levels still experience adverse bleeding. There were no intergroup differences in platelet function, determined by platelet contractile force and clot elastic modulus. Antifactor Xa poorly predicts the degree of anticoagulation in patients with ESRD administered low-molecular-weight heparin (LMWH). Thrombin generation time may be a clinically useful anticoagulation monitoring tool to monitor LMWH therapy, especially in patients with renal dysfunction. Additional randomized prospective studies are needed to corroborate these findings.


Andersson's lesion in ankylosing spondylitis diagnosed by 18F-FDG PET/CT.
Ankylosing spondylitis (AS) is a form of arthritis that affects the spine, the sacroiliac joints and sometimes the hips and shoulders. Andersson lesion (AL), was first described by Andersson in 1937 as a destructive vertebral body and discovertebral portion of the spine in AS. In this case, we report a 50 years old man with medical history of AS diagnosed AL by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).


[Transcutaneous neuromuscular electrical stimulation for the treatment of erectile dysfunction: A clinical observation].
To observe the clinical efficacy of transcutaneous neuromuscular electrical stimulation (TNES) in the treatment of ED. According to the inclusion and exclusion criteria, we included and studied 25 cases of ED treated by TNES in Northern Jiangsu People's Hospital from June 2021 to February 2022 using the self-matched pre- and post-control method. Before and after treatment, we conducted RigiScan penile hardness test under audiovisual sexual stimulation (AVSS) for all the patients and obtained their scores on the Erectile Hardness Scale (EHS), IIEF-5, Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire 9 (PHQ-9) and Generalized Anxiety Disorder Questionnaire 7 (GAD-7). No adverse reactions such as pain, allergy, skin burn, and subcutaneous congestion were observed in any of the patients. There were statistically significant differences after treatment in erection time, average and maximum hardness of the penile tip, mean hardness of the penile root, and circumference of the penile tip (P < 0.05), but not in the circumference and maximum hardness of the penile root during erection compared with the baseline (P > 0.05). Significant improvement was observed after treatment in the IIEF-5 score (P < 0.05), with a total effectiveness rate of 68%, as well as in the PEDT score (P < 0.05) GAD-7 anxiety score (P < 0.05), but not in the PHQ-9 depression score (P > 0.05). TNES, as a safe and non-invasive therapy, can improve penile hardness under AVSS and the erectile function and anxiety symptoms of ED patients, and can be used as a new option for the treatment of ED.


Self-management of oral anticoagulation therapy improves long-term survival in patients with mechanical heart valve replacement.
The Early Self-Controlled Anticoagulation Trial has demonstrated that in patients with mechanical heart valve replacement self-management of oral anticoagulation results in less major thromboembolic events than conventional measurement by the general practitioner. However, the effects of self-management on long-term survival are currently not known. Nine hundred thirty patients participated in a follow-up study of the aforementioned trial (488 from the self-management group and 442 from the conventional group). Long-term survival was assessed 12 years after the study began using the intent-to treat analysis as well as the per protocol analysis. Univariate and multivariate analyses were performed in order to assess independent predictors of survival. In total, the 930 patients accrued 8,315 patient-years of observation. During follow-up, 236 patients died. According to the intent-to treat analysis, 10-year survival was 76.1% in the conventional group and 84.5% in the self-management group. The corresponding values for the per protocol analysis were 67.7% and 80.6%, respectively. Age, kind of valve surgery, and study group were independent predictors of survival. Self-management of oral anticoagulation increased long-term survival by 23% (intent-to-treat analysis) and 33% (per protocol analysis), respectively, compared with conventional measurement by the general practitioner. Possible reasons for these advantageous results in the self-management group are fewer thromboembolic events due to a higher percentage of international normalized ratio values lying in the target range compared with the conventional group. Data indicate that self-management of oral anticoagulation is a promising strategy in order to increase long-term survival in patients with mechanical prosthetic valves.


Structural features of the human C3 gene: intron/exon organization, transcriptional start site, and promoter region sequence.
The third component of human complement (C3) is a key molecule in the activation of the complement cascade. C3 cDNA fragments were used to identify seven cosmid clones that covered all but 1 kilobase pair (kb) of the C3 gene. The remainder of the gene was cloned by using the polymerase chain reaction. These clones were used to identify the intron/exon boundaries and to map the gene. The C3 gene is 42 kb in length and comprises 41 exons ranging in size from 52 to 213 base pairs (bp). The transcription start site was identified by primer extension, and approximately 1 kb of DNA upstream of this site was sequenced. Putative TATA and CAAT boxes were identified along with a number of regions that shared homology with known regulatory sequences. These include responsive elements for interferon-gamma, interleukin-6, nuclear factor kappa B, estrogen, glucocorticoids and thyroid hormone. Several of these agents have been shown to affect C3 synthesis and mRNA levels. The sizes of the exons in C3 were compared to those of C4 and alpha 2-macroglobulin (alpha 2M). Thirty-nine of 41 exons in C4 were found to be of similar size to the analogous ones in C3, and two-thirds of those in alpha 2M were also similarly sized, supporting the hypothesis that these genes arose from a common ancestor.


Support infrastructure available to Canadian residents completing post-graduate global health electives: current state and future directions.
Global health electives offer medical trainees the opportunity to broaden their clinical horizons. Canadian universities have been encouraged by regulatory bodies to offer institutional support to medical students going abroad; however, the extent to which such support is available to residents has not been extensively studied. We conducted a survey study of Canadian universities examining the institutional support available to post-graduate medical trainees before, during, and after global health electives. Responses were received from 8 of 17 (47%) Canadian institutions. Results show that trainees are being sent to diverse locations around the world with more support than recommended by post-graduate regulatory bodies. However, we found that the content of the support infrastructure varies amongst universities and that certain components-pre-departure training, best practices, risk management, and post-return debriefing-could be more thoroughly addressed. Canadian universities are encouraged to continue to send their trainees on global health electives. To address the gaps in infrastructure reported in this study, the authors suggest the development of comprehensive standardized guidelines by post-graduate regulatory/advocacy bodies to better ensure patient and participant safety. We also encourage the centralization of infrastructure management to the universities' global health departments to aid in resource management.


[Studies on the relationship of temperent phages and bacteriocines of streptococcus faecium (author's transl)].
Two bacteriocins (enterocin E1A and E1B) as well as a complete bacteriophage (PE1) were produced by Streptococcus faecium strain E1. Although the phage could be demonstrated by electron microscopy it was not possible to observe phages or phage-like particles in the purified preparation of the large enterocin E1B. Phage PE1 had a much smaller activity spectrum than that of enterocin E1A and E1B, inhibiting only one strain of Streptococcus faecium and one strain of Streptococcus salivarius. The enterocins were not neutralized by antiphage sera, thereby suggesting that the enterocins and the phage are chemically unrelated.


Baseline CD4(+) T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients.
The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients. We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured. A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/μl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up. Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients.


Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation.
Fecal microbiota transplantation (FMT) is currently used in medicine to treat recurrent clostridial colitis and other intestinal diseases. However, neither the therapeutic mechanism of FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been clearly described. From a biological point of view, FMT can be considered a useful model for studying the ecology of host-associated microbial communities. FMT experiments can shed light on the relationship features between the host and its gut microbiota. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful for the interpretation of observed biological phenomena. Here, the recipient intestine colonization analysis tool (RECAST) novel computational approach is presented, which is based on the metagenomic read sorting process per their origin in the recipient's post-FMT stool metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning approaches, the metagenomes from three FMT studies, including healthy volunteers, patients with clostridial colitis, and patients with metabolic syndrome, were analyzed. Using our computational pipeline, the donor-derived and recipient-derived microbes which formed the recipient post-FMT stool metagenomes (successful microbes) were identified. Their presence is well explained by a higher relative abundance in donor/pre-FMT recipient metagenomes or other metagenomes from the human population. In addition, successful microbes are enriched with gene groups potentially related to antibiotic resistance, including antimicrobial peptides. Interestingly, the observed reorganization features are universal and independent of the disease. IMPORTANCE We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.


Morphofunctional evidence for the involvement of hypothalamic dopaminergic and GABAergic neurons in the mechanisms of photoperiod-dependent prolactin release in the mink.
This study was designed to examine possible relationships between the photoperiodic regulation of prolactin secretion and the activity of dopaminergic and GABAergic neurons projecting to the external layer of the median eminence. The study was carried out on the mink whose remarkable photosensitivity has been clearly demonstrated. The animals were reared in short (4L:20D) or long (20L:4D) photoperiods. The experiment began in November when day length is short (9.5 h). Dopaminergic and GABAergic neurons were studied using immunocytochemical methods allowing evaluation of the immunoreactivities of tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD), which are respective markers of these neurons. The results were quantified by image analysis. The plasma prolactin level of animals maintained in 4L:20D decreased after 60 days and TH and GAD immunoreactivity were strongly stimulated. After 110 days, the prolactin concentration and TH and GAD immunoreactivity recovered their starting levels. In animals maintained in 20L:4D, the prolactin level was 3 times higher than at the beginning of the photoperiodic treatment but only dopaminergic neurons showed a change, i.e. a decrease in immunoreactivity. At the end of the experiment, prolactin secretion was no longer affected by the stimulatory effect of long-day treatment, and TH immunoreactivity remained low. These results confirm the generally accepted concept that dopaminergic neurons are potent PIF-producing components. GABAergic hypothalamic system appears to be implicated in photoperiodic PRL regulation, but this remains to be clearly demonstrated.


Association Among Serum Insulin-Like Growth Factor-1, Frailty, Muscle Mass, Bone Mineral Density, and Physical Performance Among Community-Dwelling Middle-Aged and Older Adults in Taiwan.
Aging is featured by the complex interrelationship among body composition, frailty status, and physical performance. The main aim of this study was to evaluate the association among serum insulin-like growth factor-1 (IGF-1), body composition, and physical function among community-dwelling middle-aged and elderly population in Taiwan. We conducted a cross-sectional study by using the data of I-Lan Longitudinal Aging Study, which recruited a total of 1833 community-dwelling people aged more than 50 years. Data of lean body mass (LBM), appendicular skeletal muscle mass (ASM), total fat mass (TFM), bone mineral density (BMD) of L-spine/hip, handgrip strength, walking speed, International Physical Activity Questionnaire (IPAQ), Charlson comorbidity index (CCI), serum levels of growth hormone, IGF-1, albumin, total cholesterol, triglyceride, blood urea nitrogen, and creatinine were retrieved for analysis. The mean age of participants was 63.9 ± 9.2 years, and 47.5% were men. The serum IGF-1 level was 140.7 ± 57.6 ng/mL in men and 131.4 ± 54.5 ng/mL in women. The estimated rates of IGF-1 decline with age were 1.88 ng/mL·year in men and 2.13 ng/mL·year in women. The prevalence of frailty was 6.8% and that of prefrailty was 40.4%. After adjusting for age, albumin, IPAQ, and CCI in multiple linear regression models, LogIGF-1 was positively correlated with LBM, ASM, ASM index, height, BMD, and handgrip strength, and was inversely correlated with weakness in both genders. In men, the LogIGF-1 level was positively correlated with weight, body mass index (BMI), waist circumference, and TFM. Higher serum IGF-1 was independently associated with more muscle mass, higher BMD, and better handgrip performance in both genders. The positive association of IGF-1 with BMI, weight, TFM, and waist circumference was found in men only. Further longitudinal study to evaluate the effect of serum IGF-1 on frailty incidence is needed for its causal-effect relationship.


Survey of phytochemical composition and biological effects of three extracts from a wild plant (Cotoneaster nummularia Fisch. et Mey.): a potential source for functional food ingredients and drug formulations.
This study was focused on the analysis of the phenolic content, antioxidant, antibacterial, anti-cholinesterase, anti-tyrosinase, anti-amylase and anti-glucosidase activity of three solvent extracts from Cotoneaster nummularia. Moreover, water extract was tested in terms of mutagenic/anti-mutagenic effects. The antioxidant activities of these extracts were evaluated by DPPH, ABTS, O2, metal chelating, phosphomolybdenum, β-carotene/linoleic acid, ferric and cupric reducing power assays. Enzyme inhibitory activities were also examined with colorimetric methods. Generally, methanol and water extracts exhibited excellent biological activities. These extracts were rich in phenolic and flavonoid content. Furthermore, Cotoneaster extracts indicated appreciable antibacterial properties against human pathogen strains. HPLC analysis showed that ferulic acid, chlorogenic acid, (-) - epicatechin and (+)-catechin were the major phenolics in extracts tested. These data offer that these extracts from C. nummularia may be considered as a potential source of biological agents for developing functional foods or drug formulations.


Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells.
Polo‑like kinase 2 (PLK2) is a serine/threonine protein kinase, which has vital roles during mitosis and the centrosome cycle. In acute myeloblastic leukemia and hepatocarcinogenesis, PLK2 acts as a tumor suppressor; however, the function of PLK2 in gastric cancer remains to be elucidated. In the present study, PLK2 was overexpressed in gastric cancer tissues and three types of gastric cancer cells, SGC‑7901, MKN‑45 and BGC‑823. Transfection of SGC‑7901 gastric cancer cells with small interfering (si)RNA against PLK2 exerted no effect on the ratio of cells at different stages of the cell cycle compared with that of the untransfected and control siRNA‑transfected cells. In addition, silencing of PLK2 significantly enhanced the growth of SGC‑7901 cells through inhibiting apoptosis. Furthermore, apoptosis‑associated genes Bax and caspase 3 were found to be downregulated at the protein level. In conclusion, these results suggested that PLK2 may act as a tumor suppressor in gastric cancer, therefore indicating its therapeutic potential.


The influence of anthropometrics on physical employment standard performance.
The Canadian Armed Forces (CAF) recently implemented the Fitness for Operational Requirements of CAF Employment (FORCE), a new physical employment standard (PES). Data collection throughout development included anthropometric profiles of the CAF. To determine if anthropometric measurements and demographic information would predict the performance outcomes of the FORCE and/or Common Military Task Fitness Evaluation (CMTFE). We conducted a secondary analysis of data from FORCE research. We obtained bioelectrical impedance and segmental analysis. Statistical analysis included correlation and linear regression analyses. Among the 668 study subjects, as predicted, any task requiring lifting, pulling or moving of an object was significantly and positively correlated (r > 0.67) to lean body mass (LBM) measurements. LBM correlated with stretcher carry (r = 0.78) and with lifting actions such as sand bag drag (r = 0.77), vehicle extrication (r = 0.71), sand bag fortification (r = 0.68) and sand bag lift time (r = -0.67). The difference between the correlation of dead mass (DM) with task performance compared with LBM was not statistically significant. DM and LBM can be used in a PES to predict success on military tasks such as casualty evacuation and manual material handling. However, there is no minimum LBM required to perform these tasks successfully. These data direct future research on how we should diversify research participants by anthropometrics, in addition to the traditional demographic variables of gender and age, to highlight potential important adverse impact with PES design. In addition, the results can be used to develop better training regimens to facilitate passing a PES.


Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of ventilated rabbits.
Local administration of steroids to the lungs in ventilated newborn infants can minimize the harmful side effects that occur with systemic administration. An efficient system of drug delivery that provides uniform distribution within the lungs is essential for the treatment of bronchopulmonary dysplasia. In this study we compare surfactant with 0.9% saline solution as vehicles for the direct instillation of a steroid (budesonide) into the lungs. Twenty-two anesthetized, ventilated rabbits received [3H]budesonide in either 0.9% saline or surfactant, administered through an endotracheal tube. Before drug administration, bronchial lavage was performed on half of the animals to serve as a model for surfactant deficiency. Lung samples were analyzed by both autoradiography (alveolar versus airway distribution) and liquid scintillation counting (central versus peripheral deposition). As expected, the delivered concentration of [3H]budesonide decreased as airway size decreased and branching increased. Significantly less [3H]budesonide was deposited in the alveolar spaces of all study groups compared with that deposited in the small and large airways (p < 0.05). However, both vehicles were equally efficient in delivering [3H]budesonide to the lungs. Although the alveolar and peripheral areas received less (4-11%) of the drug than the central tissue (14-28%), this was consistent among all the groups and was not affected by altered lung compliance. Therefore, either surfactant or saline could be used to efficiently and reliably deliver budesonide to the lungs at a level greater than that reported using nebulizers. Because normal saline is currently used for tracheal toilette, it is likely to be preferred considering the increased costs associated with surfactant.


Diurnal Variation of Real-Life Insulin Sensitivity Factor Among Children and Adolescents With Type 1 Diabetes Using Ultra-Long-Acting Basal Insulin Analogs.
Estimation of insulin sensitivity factor (ISF) is essential for correction insulin doses calculation. This study aimed to assess real-life ISF among children and adolescents with type 1 diabetes using ultra-long-acting basal insulin analogs and to detect factors associated with ISF among those patients. This prospective observational study was conducted at Sohag University Hospital, Egypt, and included 93 participants aged 6-18 years, diagnosed with T1DM for at least 1 year and using insulin glargine 300 Units/mL or insulin degludec 100 Units/mL as basal insulin. The ISF, insulin-to-carbohydrate ratio (ICR) and insulin doses were initially assessed then adjusted as required. The participants were regularly contacted throughout the follow-up period. Glycemic control parameters were assessed after 3 months. The ISF showed diurnal variation with higher correction dose requirements for the morning than for the rest of the day (p < 0.001). This pattern of diurnal variation was found in participants with different pubertal stages and in participants using either type of ultra-long acting basal insulin analogs. There was no significant difference between the ISF calculated according to the 1800 rule [1800/Total daily insulin dose (TDD)] and the morning ISF (p = 0.25). The 1800 rule-calculated ISF was significantly lower than the actual ISF for the afternoon (p < 0.001) and the evening (p < 0.001). ISF at different times of the day were significantly correlated with age, body mass index, pubertal stage, diabetes duration, TDD, and ICR. Multiple regression analysis revealed that ICR was the most significant factor associated with ISF. Linear regression analysis revealed that the ISF (in mg/dL) for any time of the day could be estimated as 5.14 × ICR for the same time of the day (coefficient = 5.14, 95% confidence interval: 5.10-5.19, R 2 = 0.95, p < 0.001). Diurnal variation of ISF that had to be considered for proper calculation of correction doses. This diurnal variation was found in children and adolescents with different pubertal stages. The 1800 rule was appropriate for the morning correction doses but not in the afternoon or the evening. The TDD and the ICR could be used for ISF estimation.


Remediation capacity of Cd and Pb ions by mycelia of Imleria badia, Laetiporus sulphureus, and Agaricus bisporus in vitro cultures.
The goal of this study was to evaluate cadmium and lead accumulation ability of in vitro cultures biomass containing selected edible mushroom species derived from the environment (Laetiporus sulphureus, Imleria badia) and those of commercial origin (Agaricus bisporus). Atomic absorption spectrometry was used to evaluate the content of Cd(II) and Pb(II) on the medium supplemented with Cd(II) or Pb(II), each of them at the same concentration of 5·10-5 M. The highest concentration of Cd(II) ions was determined in the biomass from L. sulphureus in vitro cultures, while the highest concentration of Pb(II) ions was found in the biomass from A. bisporus in vitro cultures. The greatest Cd(II) and Pb(II) accumulation ability in mycelium per dry weight was shown for L. sulphureus. Among the test species, biomass of A. bisporus showed the lowest ability for the bioaccumulation of Cd(II); however, comparable ability for the remediation of Pb(II) was provided by the biomasses from A. bisporus and I. badia in vitro cultures. The results confirm the possibility of using these mushroom species for remediation and indicate the relationship between bioaccumulation of heavy metals and the test species.


[Involvement of cAMP dependent protein kinase in the reversion of a NIH/3T3 cell line transformed by a ras oncogene (EJ-NIH/3T3)].
cAMP production and the activity of cAMP dependent protein kinase (Kinase-A) were examined in a mutant clone of a NIH/3T3 cell line transformed by a human activated H-ras-1 oncogene (EJ-NIH/3T3). The mutant (R1) shows the characteristics of a flat revertant. The amount of cAMP increases more significantly in R1 than that in EJ-NIH/3T3 in the presence of PGE1. Enhanced activity of Kinase-A was also noted in R1 when compared to that in EJ-NIH/3T3. Further, EJ-NIH/3T3 treated with agents which increase intracellular cAMP content partially lost some characteristics of malignantly transformed phenotypes in vitro. These data suggest that Kinase-A might be involved in the reversion of EJ-NIH/3T3. In addition, reduced cytosolic free Ca2+ concentration measured with Ca2+ indicator in R1 cells was noted. This might also be associated with the reversion of the malignantly transformed cell line.


Neuropsychological performance of young nondrinkers, social drinkers, and long- and short-term sober alcoholics.
Neuropsychological performance of 23-42-year-old males with diverse drinking histories was assessed. Comparisons were made among nondrinkers, social drinkers, short-term sober (less than 30 days) alcoholics and long-term sober (greater than 30 days) alcoholics. Results of these comparisons provided little support for the notion that neurotoxic effects of chronic alcohol consumption are directly related to cognitive impairment. Instead, these results suggested that performance differences among the groups were more closely related to subclinical withdrawal symptoms or native ability than to long-term alcohol consumption. Because none of the dependent measures was related to length of abstinence, and because Wechsler's Adult Intelligence Scale-R Vocabulary differences among groups paralleled neuropsychological test performance differences, it is suggested that differences among groups may reflect differences in native ability. In addition, there were no differences between social drinkers and nondrinkers, nor were there any significant correlations among drinking variables and performance of social drinkers, providing further evidence against a direct relationship between alcohol consumption and cognitive performance.


Can we predict the development of symptomatic lymphocele following robot-assisted radical prostatectomy and lymph node dissection? Results from a tertiary referral Centre.
Objectives: Robot-assisted radical prostatectomy (RARP) has been established as first-line surgical therapy for organ-confined prostate cancer (PCa). Pelvic lymph node dissection (PLND) is recommended in case of intermediate and high-risk localized PCa however symptomatic lymphocele (SL) formation is a common complication. Still no certain clinical and surgical predictors of SL have been found in the robotic era. Aim of this study was to identify clinical and surgical predictors of SL after RARP and PLND.Methods: We retrospectively evaluated all consecutive patients undergone RARP and PLND from 01/2017 to 06/2019, at our institution. All procedures were performed by experienced robotic surgeons. Baseline patients' characteristics, as well as peri- and post-operative features, were recorded and compared among those patients experiencing SL after surgery and those who did not.Results: Overall, 282 patients were included. Of these, 21 (7.5%) developed SL after surgery. Patients with SL showed higher median BMI (30.4 vs 25.8) and a more frequent history of vascular surgery or lymph-vascular disease (23.8% vs 8.4%) compared to patients without SL (p < 0.05). The lymphadenectomy technique adopted during the surgery was also found different in patients diagnosed with SL. At the multivariable analysis (MVA), only the increase of BMI (OR 1.72; CI: 1.47 - 2.81) was found predictor of developing SL.Conclusion: In our experience, the increase of BMI was a significant predictor of SL development in pCa patients submitted to RARP and PLND. This further evidence may be of great help for clinicians in daily clinical practice, in particular during preoperative counseling.


Prevalence of pregnancy related oral granuloma in a Nigerian population group and the possible role of contraceptives.
A clinicopathological survey on pregnancy related tumours was carried out on 400 randomly selected pregnant Nigerian women. Fifteen (15) cases of pregnancy granuloma or 'epulis gravidanum' were found. Of these subjects, 287 representing 71.8 percent were on birth control before conception, while 113 or 28.2 percent were not. Nine (9) cases of pregnancy tumour were found in the group on birth control pills and six (6) in the group not on birth control representing an incidence of 3.1 and 5.3 percent respectively. Literature review indicate a general incidence of between 0-2.5 percent. Five of the granuloma regressed post partum, while ten were excised. Patients were followed 1-2 years post partum and no recurrence was recorded, even in patients who have re-commenced on contraceptives.


Ulcerative colitis accompanied by idiopathic thrombocytopenic purpura and Helicobacter pylori infection.
The coexistence of idiopathic thrombocytopenic purpura (ITP) and active ulcerative colitis (UC) has been reported. We herein report a rare case of UC accompanied by ITP and Helicobacter pylori (H. pylori) infection. A female UC patient was diagnosed with ITP. At that time, the UC was almost in remission and we suspected that the ITP was caused by some factor other than UC. Accordingly, we found H. pylori infection and administered H. pylori eradication therapy. Consequently, the patient's serum platelet count recovered dramatically. Our report demonstrates the importance of conducting examinations for H. pylori infection in ITP patients, even those with UC.


Effects of Nasoalveolar Molding Therapy on Alveolar and Palatal Cleft Deformities in Unilateral and Bilateral Cleft Lip and Palate.
The purpose of this study was to evaluate and compare the efficacy of nasoalveolar molding (NAM) therapy in the improvement of alveolar and palatal cleft deformity on unilateral (UCLP) versus bilateral (BCLP) cleft lip and palate. A total of 19 UCLP (14 boys and 5 girls) and 8 BCLP (7 boys and 1 girl) infants completed NAM therapy were included in this study. Standardized parameters of cleft width of alveol and palate were measured on photocopies taken from the pre- and post-treatment plaster casts. To assess the intragroup differences, paired-samples test in UCLP and Wilcoxon test in BCLP groups were used. Mann-Whitney U test was used to evaluate the differences between the groups. Significant decreases in alveolar and palatal cleft gaps were achieved in an average period of 3.3 ± 1.9 and 3.7 ± 1.6 months in UCLP and BCLP patients, respectively. The alveolar cleft decreased 7.85 ± 4.59 mm in UCLP and 4.25 ± 3.13 and 3.81 ± 3.50 mm in right and left alveolar cleft sides in BCLP, respectively. The palatal clefts were decreased 4.63 ± 2.44 mm in medial and 3.72 ± 2.62 mm in posterior parts in UCLP. The decrements in BCLP were 3.00 ± 2.75 mm in medial and 2.88 ± 2.75 mm in posterior palatal cleft distances. No significant differences were determined in the amount of alveolar or palatal cleft closure between UCLP and BCLP groups. The only decrease in arch width was 1.39 mm in medial part of palate in UCLP. The NAM device provides significant decreases in both alveolar and palatal cleft deformities in UCLP and BCLP infants, as compared with their birth status.


The Prevalence of Virulence Factors among ESBLs-Producing Klebsiella pneumoniae Isolated from Khorramabad Hospitals, Iran.
Klebsiella pneumoniae is one of the opportunistic bacteria that cause hospital infections. Various virulence factors are involved in its pathogenesis. The purpose of our study was to investigate the prevalence of virulence factor genes entB, mrkD, magA, kfu, iutA, rmpA, ybtS, and k2 among ESBLs-producing Klebsiella pneumoniae isolated from clinical samples of Khorramabad hospitals in Iran. In this descriptive, analytical study, the extended-spectrum β-lactamases (ESBLs) screening phenotypic test was performed by disc diffusion method, and virulence factor genes were detected by PCR method for Klebsiella pneumoniae isolates. Finally, the obtained data were statistically analyzed by SPSS software (version 21) using the chi-squared test. One hundred and ten K. pneumoniae strains were isolated from urine 69 (62.7%), sputum 16 (14.5%), blood 10 (9.1%), wound 9 (8.2%), tissue 3 (2.7%), body fluids 2 (1.8%), and catheter 1(0.9%). Based on an ESBL screening phenotypic test, 57 (51.8%) K. pneumoniae isolates were ESBLs-producing. Among 57 ESBLs-positive K. pneumoniae, the occurrence of mrkD, entB, ybtS, iutA, kfu, k2, and rmpA genes were 88 (80%), 87 (79.1%), 65 (59.1%), 42 (38.2%), 19 (17.3%), 5 (4.5%), 3 (2.7%), and 2 (1.8%), respectively. The findings of this study revealed, there is no significant association between the occurrence of virulence genes or source of samples with production of ESBLs among K. pneumoniae isolates.


Comparison of clinical and cost-effectiveness of two strategies using mobile digital x-ray to detect pulmonary tuberculosis in rural India.
Medanta - The Medicity, a multi-super specialty corporate hospital in Gurugram, Haryana launched a "TB-Free Haryana" Campaign; mobile van equipped with a digital CXR machine to screen patients with presumptive Tuberculosis (TB). In this study, we aimed to assess the (1) yield and cost analysis of two strategies using mobile digital x-ray to detect Pulmonary TB in rural Haryana. An observational study was conducted on all individuals screened by either of the two case finding strategies using a mobile x-ray unit (MXU) mounted on a mobile van in District Mewat, Haryana during Jan-March 2016. Strategy 1: Out of 121 smear negative cases, x-rays were suggestive of TB in 39(32%), of which 24 were started on TB treatment. Cost of identifying a smear negative TB was US$ 32. Strategy 2: Out of 596 presumptive TB, chest x-rays were suggestive of TB in 108 (18%), of which 67 were started on TB treatment (56 were smear negative TB). Cost of detecting any case of TB was US$ 08 (1 USD = 64 INR). The study reports a new initiative within a PPM model to improve the diagnosis of PTB by filling the gap in the current diagnostic infrastructure. We believe there is potential for replication of strategy 2 model in other states, although further evidence is required.


Assessing literacy for patient teaching: perspectives of adults with low literacy skills.
The purpose of this qualitative study was to gain an understanding of the response of English speaking adults with low literacy skills to screening of reading ability in order to facilitate the planning of patient teaching in a hospital setting. The Rapid Estimate of Literacy in Medicine (REALM) was the screening tool used to provide a screening experience for research subjects. A multiple case study design was employed to gain insight, describe participant experiences and generate an evidence-based conceptual model. While all participants supported the principle of screening in the context of the hospital, response to the actual experience was varied. Factors found to influence responses to screening included perceived risks of illiteracy exposure, perceived risks of non-disclosure during hospitalization and the attribution of characteristics to the hospital leading to it's designation as a 'special' place. A conceptual model of screening response was developed and compared to the Health Belief Model and Knox's Proficiency Theory of adult learning. Implications for the health professions are also discussed.


High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.
Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.


Magnesium Deficiency Induced Global Transcriptome Change in Citrus sinensis Leaves Revealed by RNA-Seq.
Magnesium (Mg) deficiency is one of the major constraining factors that limit the yield and quality of agricultural products. Uniform seedlings of the Citrus sinensis were irrigated with Mg deficient (0 mM MgSO4) and Mg sufficient (1 mM MgSO4) nutrient solutions for 16 weeks. CO2 assimilation, starch, soluble carbohydrates, TBARS content and H2O2 production were measured. Transcriptomic analysis of C. sinensis leaves was performed by Illumina sequencing. Our results showed that Mg deficiency decreased CO2 assimilation, but increased starch, sucrose, TBARS content and H2O2 production in C. sinensis leaves. A total of 4864 genes showed differential expression in response to Mg deficiency revealed by RNA-Seq and the transcriptomic data were further validated by real-time quantitative PCR (RT-qPCR). Gene ontology (GO) enrichment analysis indicated that the mechanisms underlying Mg deficiency tolerance in C. sinensis may be attributed to the following aspects: a) enhanced microtubule-based movement and cell cycle regulation; b) elevated signal transduction in response to biotic and abiotic stimuli; c) alteration of biological processes by tightly controlling phosphorylation especially protein phosphorylation; d) down-regulation of light harvesting and photosynthesis due to the accumulation of carbohydrates; e) up-regulation of cell wall remodeling and antioxidant system. Our results provide a comprehensive insight into the transcriptomic profile of key components involved in the Mg deficiency tolerance in C. sinensis and enrich our understanding of the molecular mechanisms by which plants adapted to a Mg deficient condition.


Background sodium current underlying respiratory rhythm regularity.
Rhythm-generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states--thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or 'stable' respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing. We used a mouse in vitro medullary slice preparation containing the rhythmogenic respiratory neural circuit, called the preBötzinger complex (preBötC), that underlies inspiratory respiratory activity. We varied either [K(+)](o) or [Na(+)](o), or blocked voltage-gated calcium channels, while recording from synaptically isolated respiratory pacemakers, and examined which of these manipulations resulted in their endogenous bursting becoming more irregular. Of these, lowering [Na(+)](o) increased the irregularity of endogenous bursting by synaptically isolated pacemakers. Lowering [Na(+)](o) also decreased the regularity of fictive eupneic activity generated by the ventral respiratory group (VRG) population and hypoglossal motor output. Voltage clamp data indicate that lowering [Na(+)](o), in a range that results in irregular population rhythm generation, decreased persistent sodium currents, but not transient sodium currents underlying action potentials. Our data suggest that background sodium currents play a major role in determining the regularity of the fictive eupneic respiratory rhythm.


Up-regulation of p21(WAF1/CIP1) levels leads to growth suppression of prostate cancer cell lines.
In a previous study, we found that TPA-mediated up-regulation of p21(WAF1/CIP1) induces growth arrest and differentiation of the human prostate cancer cell line TSU-Pr1. We investigated the effect of 12-O-tetra-decanoylphorbol-13-acetate (TPA) on growth and p21(WAF1/CIP1) protein levels in four prostate cancer cell lines. TPA treatment suppressed proliferation of the androgen-insensitive prostate cancer cell lines DU145 and PC-3. DU145 and PC-3 cells, however, showed neither morphological changes nor differentiation after TPA treatment. In contrast, TPA induced apoptosis of the androgen-sensitive prostate cancer cell line LNCaP. TPA induced up-regulation of p21(WAF1/CIP1) protein levels in all four cancer cell lines and this up-regulation was regulated by PKC in all four, but MAP kinase was associated with regulation only in TSU-Pr1 cells. Moreover, transient transfection with Adv-p21 resulted in growth arrest of all four cell lines. These data suggest that increased p21(WAF1/CIP1) production directly suppresses proliferation of prostate cancer cells regardless of androgen sensitivity. The pathway of TPA-induced increases in p21(WAF1/CIP1) levels was regulated by PKC. We thus conclude that p21(WAF1/CIP1) is a good candidate for use in treatment of prostate cancers because it suppresses proliferation of several prostate cancer cell lines.


BROMINE ANALYSIS IN 5-BROMOURACIL-LABELED DNA BY X-RAY FLUORESCENCE.
The degree of replacement of thymine by 5-bromouracil in the deoxyribonucleic acid (DNA) of the thymine-deficient bacterium Escherichia coli B 15 T(-) has been determined by a nondispersive x-ray fluorescence method. A measure of the fraction by weight of bromine in the purified DNA is required for determining the degree of thymine replacement. This fraction is experimentally determined on 35-microg samples of DNA by x-ray spectroanalysis.


Multi-Stimuli-Responsive Fluorescence Switching from a Pyridine-Functionalized Tetraphenylethene AIEgen.
The discovery of the striking aggregation-induced emission (AIE) phenomenon has opened a new avenue for smart light-emitting materials. Herein, a new AIE luminogen (AIEgen), 1,1,2,2-tetrakis(4-((E)-2-(pyridin-2-yl)vinyl)phenyl)ethene (TP2VPE), has been designed and synthesized by introducing the vinylpyridine motifs into the tetraphenylethene backbone. The emission spectrum of the new obtained AIEgen crystalline material can be switched in response to not only mechanical grinding and hydrostatic compression but also the protonation effect with excellent reversibility and reproducibility. Single-crystal X-ray structural analysis disclosed the supramolecular porous channel structure, which provides a shrinkable volume to maintain the fluorescence emission upon high pressure. Furthermore, protonation-deprotonation of the pyridine moieties in TP2VPE has a significant effect on the frontier molecular orbitals as well as very distinctive emission characteristics upon acid and base stimuli. The dual-response performance and the ease of its preparation and renewal endow the material with potential applications in pressure and acid/alkali fluorescence sensing.


Time series analysis of personal exposure to ambient air pollution and mortality using an exposure simulator.
This paper describes a modeling framework for estimating the acute effects of personal exposure to ambient air pollution in a time series design. First, a spatial hierarchical model is used to relate Census tract-level daily ambient concentrations and simulated exposures for a subset of the study period. The complete exposure time series is then imputed for risk estimation. Modeling exposure via a statistical model reduces the computational burden associated with simulating personal exposures considerably. This allows us to consider personal exposures at a finer spatial resolution to improve exposure assessment and for a longer study period. The proposed approach is applied to an analysis of fine particulate matter of <2.5 μm in aerodynamic diameter (PM(2.5)) and daily mortality in the New York City metropolitan area during the period 2001-2005. Personal PM(2.5) exposures were simulated from the Stochastic Human Exposure and Dose Simulation. Accounting for exposure uncertainty, the authors estimated a 2.32% (95% posterior interval: 0.68, 3.94) increase in mortality per a 10 μg/m(3) increase in personal exposure to PM(2.5) from outdoor sources on the previous day. The corresponding estimates per a 10 μg/m(3) increase in PM(2.5) ambient concentration was 1.13% (95% confidence interval: 0.27, 2.00). The risks of mortality associated with PM(2.5) were also higher during the summer months.


The Prx1 homeobox gene is critical for molar tooth morphogenesis.
The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1(-/-)/Prx2(-/-) neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998, 2001; Lu et al., 1999), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development in Prx1(-/-)/Prx2(-/-) embryos to determine whether the tooth malformation is primary to the loss of Prx protein or secondary to defects in surrounding tissues. Three-dimensional (3D) morphological reconstructions demonstrated that Prx1(-/-)/Prx2(-/-) embryos had molar malformations, including cuspal changes and ectopic epithelial projections. Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D reconstructions showed important morphological defects in epithelial tissues at the cap and bell stages. Analysis of these data suggests that the Prx homeoproteins are critical for mesenchymal-epithelial signaling during tooth morphogenesis.


Interaction of carbapenems and β-lactamase inhibitors towards CTX-M-15 and CTX-M-15G238C mutant.
The aim of this study was to evaluate the role of residue 238 in CTX-M-15 and CTX-M-15G238C mutant with respect to carbapenems and various β-lactamase inhibitors. A CTX-M-15G238C laboratory mutant was generated by site-directed mutagenesis from CTX-M-15 enzyme by replacing glycine 238 with cysteine. Thiol titration and p-chloromercuribenzoate (PCMB) inactivation assays were used to ascertain the presence of a disulfide bridge in the active site of CTX-M-15G238C. Kinetic parameters were determined both for CTX-M-15 and CTX-M-15G238C enzymes by analysing either the complete hydrolysis time courses or under initial rate conditions. In CTX-M-15G238C mutant, the two cysteines (C69 and C238) located in the enzyme active site were unable to form a disulfide bridge. CTX-M-15 and thermostable CTX-M-15G238C were used to study the kinetic interaction with carbapenems, which behaved as poor substrates for both enzymes. Meropenem and ertapenem acted as transient inactivators for CTX-M-15 and CTX-M-15G238C, and for these compounds the variation of kobs versus the inactivator concentration was linear. Imipenem behaved as a transient inactivator for CTX-M-15 and as an inactivator (with k+3=0) for CTX-M-15G238C. In any case, the k+2/K values for CTX-M-15G238C were higher than those for CTX-M-15. Compared with CTX-M-15, CTX-M-15G238C mutant appears to have a more favourable conformation for carbapenem acylation and higher activity against cefotaxime, which could be due to the presence of free -SH groups in the enzyme active site.


Transition to intermittent chaotic synchronization.
Coupled chaotic oscillators can exhibit intermittent synchronization in the weakly coupling regime, as characterized by the entrainment of their dynamical variables in random time intervals of finite duration. We find that the transition to intermittent synchronization can be characteristically distinct for geometrically different chaotic attractors. In particular, for coupled phase-coherent chaotic attractors such as those from the Rössler system, the transition occurs immediately as the coupling is increased from zero. For phase-incoherent chaotic attractors such as those in the Lorenz system, the transition occurs only when the coupling is sufficiently strong. A theory based on the behavior of the Lyapunov exponents and unstable periodic orbits is developed to understand these distinct transitions.


Cancer incidence among male pesticide applicators in the Agricultural Health Study cohort exposed to diazinon.
Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.


Intraoesophageal rupture of a thoracic aortic aneurysm.
The intraoesophageal rupture of a large thoracic aortic aneurysm is reported in a 49 year old man. He had been hypertensive for some years while the aneurysm increased in size. Although a graft was successfully inserted to repair the leak, infection from the oesophagus with candida albicans, subsequently led to secondary haemorrhage and death 17 days later. A plea is made for the earlier referral of patients with aneurysm prior to rupture, as the operative mortality rises markedly after rupture has occurred and in this case the situation was virtually irreparable.


Fabrication of poly(3-hexylthiophene) thin films by vapor-phase polymerization for optoelectronic device applications.
The vapor-phase polymerization (VPP) of poly(3-hexylthiophene) (P3HT) was achieved successfully as an alternative method to conventional solution-based thin film fabrication. Using Fe(III)Cl(3).6H(2)O, a spontaneous reaction of 3-hexylthiophene monomers resulted in the rapid formation of conducting P3HT thin films directly on substrates, such as glass, indium-tin-oxide, and poly(ethylene terephthalate), at thicknesses ranging from 50 to 1000 nm. The VPP of P3HT was achieved using ferric chloride hexahydrate and a 1:1 ratio of a methanol/ethanol mixture as the solvent system. The developed VPP technique can provide good processing consistency with an electrical conductivity, a transmittance, and a surface roughness of approximately 10(-2) S/cm, >90%, and <10 nm, respectively.


Perioperative administration of high-dose recombinant human erythropoietin for delayed graft function prevention in kidney transplantation: a meta-analysis.
Delayed graft function (DGF) due to ischemia-reperfusion injury is a major early complication of kidney transplantation (KT). Recombinant human erythropoietin (rHuEPO) has been shown to exert nephroprotective action in animal models. We conducted a meta-analysis to explore the impact of rHuEPO on DGF in KT. Eligible studies comparing perioperative high-dose rHuEPO with placebo or no therapy for prevention of DGF were identified through MEDLINE, CENTRAL, and Transplant Library. Their design and data were assessed by two independent reviewers. Among 737 examined studies, four randomized controlled trials, involving 356 recipients of kidney allografts from deceased donors, fulfilled inclusion criteria. Statistical heterogeneity across studies was not significant (P = 0.98, I(2) = 0%). In a random effects model, no significant difference was found in the occurrence of DGF (odds ratio: 0,74, 95% CI: 0.47-1.18, P = 0.21). At 4 weeks after KT, the rHuEPO group exhibited higher systolic blood pressure (mean difference: 6.47 mmHg, 95% CI: 1.25-11.68, P = 0.02). Perioperative, high-dose rHuEPO administration does not prevent DGF in deceased donor KT. Furthermore, it is associated with higher systolic blood pressure leading to safety concerns. Nonerythropoietic rHuEPO derivatives, designed for nephroprotective action without increasing cardiovascular risk, might prove an alternative but still are at early stages of development.


Shortness of breath after AV ablation: case of left phrenic nerve palsy.
Phrenic nerve palsy has been recognized as a complication of catheter ablation with a prevalence of 0.11-0.48% after atrial fibrillation ablation, independent of the type of ablation catheter or energy source, likely due to the anatomical relationship of the nerves. This report describes a case of new onset of shortness of breath (SOB) due to left diaphragm paralysis following transcatheter radiofrequency ablation in a patient with underlying chronic obstructive pulmonary disease.


Aging With a Physical Disability in Medicaid Managed Care.
This study examines health services appraisal (HSA) and unmet health-care needs for adults (age 50 and over) with physical disabilities in Medicaid managed care (MMC) versus Medicaid fee for service (FFS). Surveys from 309 individuals in MMC and 349 in FFS 2 years after MMC implementation included demographics, MMC processes, HSA, and unmet health-care needs. Regression analyses with HSA and unmet health-care needs as outcomes included demographics and group status (MMC or FFS) for the entire sample, and demographics and MMC processes (continuity of care, experience with care coordinators and primary care physicians) as independent variables for only MMC enrollees. Group status was not associated with HSA or unmet needs. Among MMC enrollees, better health and more positive MMC processes related to higher HSA and lower unmet needs. It is important to consider the perspectives of people aging with disabilities in MMC to better serve their needs.


Working towards recalcitrance mechanisms: increased xylan and homogalacturonan production by overexpression of GAlactUronosylTransferase12 (GAUT12) causes increased recalcitrance and decreased growth in Populus.
The development of fast-growing hardwood trees as a source of lignocellulosic biomass for biofuel and biomaterial production requires a thorough understanding of the plant cell wall structure and function that underlie the inherent recalcitrance properties of woody biomass. Downregulation of GAUT12.1 in Populus deltoides was recently reported to result in improved biomass saccharification, plant growth, and biomass yield. To further understand GAUT12.1 function in biomass recalcitrance and plant growth, here we report the effects of P. trichocarpa GAUT12.1 overexpression in P. deltoides. Increasing GAUT12.1 transcript expression by 7-49% in P. deltoides PtGAUT12.1-overexpression (OE) lines resulted in a nearly complete opposite biomass saccharification and plant growth phenotype to that observed previously in PdGAUT12.1-knockdown (KD) lines. This included significantly reduced glucose, xylose, and total sugar release (12-13%), plant height (6-54%), stem diameter (8-40%), and overall total aerial biomass yield (48-61%) in 3-month-old, greenhouse-grown PtGAUT12.1-OE lines compared to controls. Total lignin content was unaffected by the gene overexpression. Importantly, selected PtGAUT12.1-OE lines retained the recalcitrance and growth phenotypes upon growth for 9 months in the greenhouse and 2.8 years in the field. PtGAUT12.1-OE plants had significantly smaller leaves with lower relative water content, and significantly reduced stem wood xylem cell numbers and size. At the cell wall level, xylose and galacturonic acid contents increased markedly in total cell walls as well as in soluble and insoluble cell wall extracts, consistent with increased amounts of xylan and homogalacturonan in the PtGAUT12.1-OE lines. This led to increased cell wall recalcitrance, as manifested by the 9-15% reduced amounts of recovered extractable wall materials and 8-15% greater amounts of final insoluble pellet in the PtGAUT12.1-OE lines compared to controls. The combined phenotype and chemotype data from P. deltoides PtGAUT12.1-OE and PdGAUT12.1-KD transgenics clearly establish GAUT12.1 as a recalcitrance- and growth-associated gene in poplar. Overall, the data support the hypothesis that GAUT12.1 synthesizes either an HG-containing primer for xylan synthesis or an HG glycan required for proper xylan deposition, anchoring, and/or architecture in the wall, and the possibility of HG and xylan glycans being connected to each other by a base-sensitive covalent linkage.


Virus-like particle-based nanocarriers as an emerging platform for drug delivery.
New nanocarrier technologies are emerging, and they have great potential for improving drug delivery, targeting efficiency and bioavailability. Virus-like particles (VLPs) are natural nanoparticles from animal and plant viruses and bacteriophages. Hence, VLPs present several great advantages, such as morphological uniformity, biocompatibility, reduced toxicity and easy functionalisation. VLPs can deliver many active ingredients to the target tissue and have great potential as a nanocarrier to overcome the limitations associated with other nanoparticles. This review will focus primarily on the construction and applications of VLPs, particularly as a novel nanocarrier to deliver active ingredients. Herein, the main methods for the construction, purification and characterisation of VLPs, as well as various VLP-based materials used in delivery systems are summarised. The biological distribution of VLPs in drug delivery, phagocyte-mediated clearance and toxicity are also discussed.


Levels of microRNA-181b and plasminogen activator inhibitor-1 are associated with hypertensive disorders complicating pregnancy.
The aim of the present study was to explore the association between the expression of microRNA (miRNA)-181b and plasminogen activator inhibitor-1 (PAI-1) in the placental tissue of pregnant females with a hypertensive disorder complicating pregnancy (HDCP). Placental tissue samples were obtained from 48 patients with HDCP and 40 females with a normal pregnancy. The levels of miRNA-181b and PAI-1 mRNA were determined by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of PAI-1 protein was analyzed by western blotting. Vascular smooth muscle cells (VSMCs) were transfected with the pEGP-miRNA-181b plasmid using Lipofectamine® 2000. Transfection efficiency was confirmed by immunohistochemical analysis. The levels of miRNA-181b in the placental tissue of patients with HDCP were lower than those in the control group, whereas the levels of PAI-1 mRNA in the placental tissue of patients with HDCP were higher than those in the control group. The expression of the PAI-1 protein in the HDCP group was higher than that in the control group. Following transfection of VSMCs with plasmid pGCMV/EGFP/miRNA-181b, the levels of PAI-1 mRNA were reduced while the levels of miRNA-181 were upregulated. Furthermore, the expression levels of PAI-1 protein were lower than those in the control group. The levels of miRNA-181b and PAI-1 mRNA were strongly associated with HDCP. Thus, miRNA-181b may play an important role in the regulation of PAI-1. PAI-1 and miRNA-181b may be novel biomarkers to be used in HDCP therapy.


The potato sucrose transporter StSUT1 interacts with a DRM-associated protein disulfide isomerase.
Organization of proteins into complexes is crucial for many cellular functions. Recently, the SUT1 protein was shown to form homodimeric complexes, to be associated with lipid raft-like microdomains in yeast as well as in plants and to undergo endocytosis in response to brefeldin A. We therefore aimed to identify SUT1-interacting proteins that might be involved in dimerization, endocytosis, or targeting of SUT1 to raft-like microdomains. Therefore, we identified potato membrane proteins, which are associated with the detergent-resistant membrane (DRM) fraction. Among the proteins identified, we clearly confirmed StSUT1 as part of DRM in potato source leaves. We used the yeast two-hybrid split ubiquitin system (SUS) to systematically screen for interaction between the sucrose transporter StSUT1 and other membrane-associated or soluble proteins in vivo. The SUS screen was followed by immunoprecipitation using affinity-purified StSUT1-specific peptide antibodies and mass spectrometric analysis of co-precipitated proteins. A large overlap was observed between the StSUT1-interacting proteins identified in the co-immunoprecipitation and the detergent-resistant membrane fraction. One of the SUT1-interacting proteins, a protein disulfide isomerase (PDI), interacts also with other sucrose transporter proteins. A potential role of the PDI as escort protein is discussed.


Genetics of psoriasis.
Psoriasis is a common and debilitating immune-mediated skin disease with a complex genetic basis. Genetic studies have provided critical insights into the pathogenesis of disease. This article focuses on the results of genetic association studies, which provide evidence that psoriasis susceptibility genes are involved in innate and adaptive immunity and skin barrier functions. The potential for disease stratification and the development of more effective treatments with fewer side effects using genetic data are highlighted.


GASA Proteins: Review of Their Functions in Plant Environmental Stress Tolerance.
Gibberellic acid-stimulated Arabidopsis (GASA) gene family is a class of functional cysteine-rich proteins characterized by an N-terminal signal peptide and a C-terminal-conserved GASA domain with 12 invariant cysteine (Cys) residues. GASA proteins are widely distributed among plant species, and the majority of them are involved in the signal transmission of plant hormones, the regulation of plant development and growth, and the responses to different environmental constraints. To date, their action mechanisms are not completely elucidated. This review reports an overview of the diversity, structure, and subcellular localization of GASA proteins, their involvement in hormone crosstalk and redox regulation during development, and plant responses to abiotic and biotic stresses. Knowledge of this complex regulation can be a contribution to promoting multiple abiotic stress tolerance with potential agricultural applications through the engineering of genes encoding GASA proteins and the production of transgenic plants.


Macrophage regulation of the "second brain": CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the Cx3cr1-Dtr rat model.
Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout Cx3cr1-Dtr (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized ex vivo video imaging to evaluate colonic motility. Our previous studies in brain suggested that Cx3cr1-expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed.


[Influence of bone marrow fat on the determination of bone mineral content by QCT].
Single-energy quantitative CT (SEQCT) is thought to be suitable for long-term observation of changes in bone mineral content in individual patients. However, in patients with osteoporosis, an increase in bone marrow fat cannot be ignored. The relationship between bone marrow fat and bone mineral density (BMD) at different tube voltages of 80 kV and 120 kV was investigated using a set of solution phantoms that we devised, and was also studied in healthy volunteers. On the basis of the results obtained using the solution phantoms, the influence of bone marrow fat accounted for a decrease of 8.9 mg/cm3 in BMD value at 80 kV and of 10.8 mg/cm3 at 120 kV in the presence of 10 vol% fat. These findings suggested that the influence of fat was less at a lower tube voltage. The formulas used to estimate the true bone mineral and fat contents from the BMD values at low and high tube voltages were derived by eliminating the influence of beam hardening. Using these formulas, we studied healthy volunteers, and found that the difference between the true BMD value and the BMD value calibrated for beam hardening averaged 17.8 mg/cm3 at 80 kV and 22.6 mg/cm3 at 120 kV. Moreover, the estimated concentration of bone marrow fat in the volunteers averaged 25.0 vol%. In conclusion, because SEQCT performed at a low tube voltage is less influenced by bone marrow fat, it should be selected for assessment of the clinical response to therapy and for studying sequential changes. However, in patients with a low bone mineral content indicated by SEQCT, it would be worthwhile trying to estimate both true mineral and fat contents in bone using the formulas obtained in this study in order to differentiate decrease in bone mineral from interference by bone marrow fat.


[Accurate reconstruction of traumatic bony contour defects of periobital area with prefabricated silastic].
The silicone inlay method of prefabricating subcutaneous and bony implants for congenital and acquired defects of the maxillofacial area was used in 25 cases. Heat vulcanized Silastic 372 or 373 was used, and seems to be satisfactory. The method is presented as a useful addition to the surgical restoration of subcutaneous and bony defects, particularly complex contours of the periorbital area when autogenous tissue is unavailable. Complications seem to be less common when the implant is immobile and secured to bone. The method is evolving, and modifications can and should be made in the technique.


Magnetic, magneto-optic and magnetotransport properties of nanocrystalline Co/Au multilayers with ultrathin Au interlayers.
A series of nanocrystalline Co/Au multilayers with ultrathin Au interlayers was grown at room temperature by electron beam evaporation on Si(111), glass and polyimide substrates. X-ray diffraction measurements reveal a face centered cubic multilayered structure with very small nanograins within 7-10 nm in diameter. Magneto-optic polar Kerr effect experiments show an enhancement of the Kerr rotation around 3 eV as the Au interlayer thickness increases. The experimental data are interpreted with the help of simulated Kerr spectra. The magnetization curves and magnetic force microscopy images indicate the existence of perpendicularly magnetized stripe-domain structures at remanence. The magnitude of the magnetoresistance ratio reaches values of 0.4%. The investigation of the interplay between magnetic and magnetotransport properties demonstrates the contribution of the domain-wall spin-dependent scattering to the magnetoresistance.


Review of imaging in post-laparoscopy cholecystectomy complications.
Laparoscopic cholecystectomy is now considered the procedure of choice for uncomplicated symptomatic gallstone disease worldwide. Various biliary, vascular, gastrointestinal, neurological and local complications may be seen on imaging post surgery. Knowledge of these entities and imaging appearances is indispensable for the radiologist in today's era. We emphasize on the list of potential complications and imaging appearances of this surgical procedure.


Update on pharmacologic approaches to prevent thromboembolism in atrial fibrillation: are thrombin and factor Xa inhibitors the ultimate answer?
Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. Prevalence and incidence rates are rising with the advancing population age. A severe complication of untreated AF is thrombus formation in the left atrial appendage with consecutive peripheral thromboembolism. Thus, AF is a major contributor to thromboembolic events, especially in the elderly. Depending on the CHADS2 score for thromboembolic events that takes into account congestive heart failure, hypertension, age, diabetes mellitus and stroke as risk factors, oral anticoagulation therapy with vitamin K antagonists is currently the treatment of choice for the prevention of thromboembolism. However, due to drawbacks of current anticoagulation therapy new substances for oral therapy are currently evaluated in various clinical studies. This article provides an up to date overview of orally active compounds for the future treatment of AF. Emphasis lies on comparison of direct thrombin inhibitors with factor Xa inhibitors that are currently investigated in clinical phase III studies for the treatment of non-valvular AF. The direct thrombin inhibitor dabigatran will be compared with factor Xa inhibitors like rivaroxaban and apixaban. Other promising agents currently investigated in phase II trials such as direct factor Xa inhibitors DU-176b (edoxaban) and YM150, will also be discussed.