Molecular chaperones in the etiology and therapy of cancer.
Molecular chaperones are ubiquitous, well-conserved proteins that account for 2-5 % of all cellular proteins in most cells. The present review summarizes our current knowledge about their involvement in the etiology and therapy of cancer with special emphasis on the expression of chaperones in malignant cells, their role in folding of (proto)oncogene products, cell cycle regulation, cell differentiation and apoptosis, development of metastasis, and their participation in the recognition of malignant cells. We also overview the importance of chaperones in hyperthermia, drug resistance, and recent approaches in chaperone-immunotherapy.


HDlive ultrasound images in assisted reproduction treatment.
The volume ultrasound technology software known as the HDlive technique represents an innovative tool, a step towards an even more realistic anatomical visualization of pelvic organ structures. HDlive can help improve physician-patient communication with the aid of life-like images and might prove useful in the field of assisted reproduction treatment. The clinical application of this novel ultrasound technology in assisted reproduction treatment deserves scientific evaluation.


The monoclonal antibody AG-1, a potent stimulator of human platelets, interacts with a low molecular weight GTP-binding protein.
AG-1 is a monoclonal antibody that binds to human platelets and causes aggregation and secretion. Previous work has established that these responses result from phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). To determine the mechanism by which this ligand induces signals for platelet activation, we performed a series of experiments examining the platelet binding site for AG-1. AG-1 immunoprecipitates from radioiodinated human platelet plasma membranes a protein of Mr 21,000. AG-1 immunoprecipitated proteins separated by SDS-PAGE, transferred to nitrocellulose, and incubated with [alpha 32P]GTP demonstrate binding of the radiolabeled GTP to the Mr 21,000 protein. A 100-fold molar excess of unlabeled GTP inhibits completely this binding of [alpha 32P]GTP. These results indicate that AG-1 interacts with a low Mr GTP-binding protein on the surface of platelets and suggests that either the protein recognized by AG-1 or a coprecipitating molecule of similar Mr is a low Mr GTP-binding protein that may function in platelet extracellular signal transduction.


Standardized generation and differentiation of neural precursor cells from human pluripotent stem cells.
Precise, robust and scalable directed differentiation of pluripotent stem cells is an important goal with respect to disease modeling or future therapies. Using the AggreWell™400 system we have standardized the differentiation of human embryonic and induced pluripotent stem cells to a neuronal fate using defined conditions. This allows reproducibility in replicate experiments and facilitates the direct comparison of cell lines. Since the starting point for EB formation is a single cell suspension, this protocol is suitable for standard and novel methods of pluripotent stem cell culture. Moreover, an intermediate population of neural precursor cells, which are routinely >95% NCAM(pos) and Tra-1-60(neg) by FACS analysis, may be expanded and frozen prior to differentiation allowing a convenient starting point for downstream experiments.


Triple IVC: a combination of periureteral venous ring and left IVC.
Variations of the inferior vena cava (IVC) are clinically silent and most often diagnosed incidentally when imaging for other reasons. However, they may have significant clinical implications during retroperitoneal surgery, venous intervention, or differential imaging diagnosis. This article describes a case of triple IVC, discovered on a lumbar CT and MRI scan during an evaluation of back pain.


Decompression of tension pneumothoraces in Asian trauma patients: greater success with lateral approach and longer catheter lengths based on computed tomography chest wall measurements.
Our study aims to compare the anterior and lateral approaches for needle thoracostomy (NT) and determine the adequacy of catheter lengths used for NT in Asian trauma patients based on computed tomography chest wall measurements. A retrospective review of chest computed tomography scans of 583 Singaporean trauma patients during period of 2011-2015 was conducted. Four measurements of chest wall thickness (CWT) were taken at the second intercostal space, midclavicular line and fifth intercostal space, midaxillary line bilaterally. Measurements were from the superficial skin layer of the chest wall to the pleural space. Successful NT was defined radiologically as CWT ≤ 5 cm. There were 593 eligible subjects. Mean age was 49.1 years (49.1 ± 21.0). Majority were males (77.0%) and Chinese (70.2%). Mean CWT for the anterior approach was 4.04 cm (CI 3.19-4.68) on the left and 3.92 cm (CI 3.17-4.63) on the right. Mean CWT for the lateral approach was 3.52 cm (CI 2.52-4.36) on the left, and 3.62 cm (CI 3.65-4.48) on the right. Mean CWT was shorter in the lateral approach by 0.52 cm on the left and 0.30 cm on the right (p = 0.001). With a 5.0 cm catheter in the anterior approach, 925 out of 1186 sites (78.8%) will have adequate NT as compared to 98.2% with a 7.0 cm catheter. Similarly, in the lateral approach 1046 out of 1186 (88.2%) will have adequate NT as compared to 98.5% with a 7.0 cm catheter. Obese subjects had significantly higher mean CWT in both approaches (p = 0.001). There was moderate correlation between BMI and CWT in the anterior approach, r 2 = 0.529 as compared to the lateral approach, r 2 = 0.244. Needle decompression using the lateral approach or a longer catheter is more likely to succeed in Asian trauma patients. A high BMI is an independent predictor of failure of NT, especially for the anterior as compared to lateral approach.


An outbreak of Lawsonia intracellularis infection in a standardbred herd in Ontario.
An outbreak of protein-losing enteropathy associated with Lawsonia intracelluaris infection was diagnosed in 6 standardbred foals from a farm in Ontario. Wildlife exposure may have been involved in the perpetuation of disease in this outbreak. The clinical presentation, treatment, outcomes, and pathological findings are described.


A concise review on the role of LINC00324 in different cancers.
Long intergenic non-protein coding RNA 324 (LINC00324) is an example of lncRNAs whose roles in the carcinogenesis is being elucidated. This lncRNA is encoded by a gene located on 17p13.1. It has been shown to be over-expressed in a variety of cancer cell lines and tumoral tissues. However, there are few reports showing down-regulation of LINC00324 in cancer cell lines and tissues. miR-615-5p/AKT1, miR-139-5p/IGF1R, miR-769-5p/STAT3, miR-3200-5p/BCAT1 and miR-214-5p/CDK6/CCND1/MDM2/MDM4 are examples of miRNA/mRNA axes being influenced by LINC00324. LINC00324 can be regarded as a promising candidate for development of diagnostic and prognostic panels. Moreover, it can be used a therapeutic target for a wide range of cancers. The current review summarizes the evidence regarding the impact of lINC00324 in the carcinogenic processes.


Aberrant methylation of human L- and M-fructose 1,6-bisphosphatase genes in cancer.
A possible epigenetic regulation of the two isoenzymes of fructose 1,6-bisphosphatase (FBPase) was studied in liver, muscle, mamma, breast cancer and in different cancer cell lines. Results obtained after bisulfite sequencing revealed a different CpG methylation of both promoters in liver, muscle and breast tissue which is putatively involved in the cell-type specific gene expression of the two enzymes. In tumor cell lines, demethylation with 5-aza-deoxycytidine activated the expression of both isoenzymes. Additional inhibition of histone deacetylase with trichostatin A further increased FBPase mRNA concentrations. Since cancers typically have an abnormal energy metabolism and exhibit a low gluconeogenic phenotype, it was studied whether promoter methylation contributes to the decreased expression of FBPase in breast cancer. When non-malignant and malignant tissue samples from the same patient were compared a correlation between an increase of FBPase promoter methylation and a decrease of FBPase mRNA levels was observed.


α-Amidoamids as New Replacements of Antibiotics-Research on the Chosen K12, R2-R4 E. coli Strains.
A preliminary study of α-amidoamids as new potential antimicrobial drugs was performed. Special emphasis was placed on selection of structure of α-amidoamids with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R1-R4 (with different length LPS in its structure) were used. The presented work showed that the antibacterial activity of α-amidoamids depends on their structure and affects the LPS of bacteria. Moreover, the influence of various newly synthesized α-amidoamids on bacteria possessing smooth and rought LPS and oxidative damage of plasmid DNA caused by all newly obtained compounds was indicated. The presented studies clearly explain that α-amidoamids can be used as substitutes for antibiotics. The chemical and biological activity of the analysed α-amidoamids was associated with short alkyl chain and different isocyanides molecules in their structure such as: tetr-butyl isocyanide or 2,5-dimethoxybenzyl isocyanide. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.


Variation in melatonin receptors (Mel(1a) and Mel(1b)) and androgen receptor (AR) expression in the spleen of a seasonally breeding bird, Perdicula asiatica.
Daily variation in the peripheral level of melatonin plays a major role in integrating reproduction and environmental information for seasonally breeding birds. However, the variation in immunity and reproduction has never been assessed in any avian species on a 24 h time scale. Therefore, to understand the relationship between immune function and reproductive phases in a seasonally breeding bird, Perdicula asiatica, the Indian jungle bush quail, we studied the daily variation of melatonin and testosterone levels along with expression of their receptors Mel(1a), Mel(1b), and androgen receptor in the spleen during the reproductively active phase. Immunocytochemistry for the melatonin receptors Mel(1a) and Mel(1b) presented a differential distribution pattern. Western blot of splenic protein suggested a daily rhythm of melatonin receptors, while acrophases for the two melatonin receptors Mel(1a) and Mel(1b) differed by 4 h, suggesting that the expression of the receptors may peak at different times, causing more of either Mel(1a) or Mel(1b) to be available at a particular time to mediate function. The circulatory melatonin level correlated with percentage stimulation ratio of splenocytes and plasma interleukin-2 level, but did not correlate with testosterone or androgen receptor, suggesting that melatonin could be a major hormone imparting a time-of-day effect on the modulation of immune function in a seasonally breeding bird during the reproductively active phase.


Prospective associations between social support and posttraumatic stress disorder may be spurious: A re-meta-analysis of longitudinal studies and a simulation.
A recent meta-analysis concluded to have found proof for both a social causation model, according to which social support protects against posttraumatic stress disorder (PTSD), and a social selection model, which claims that PTSD erodes social support. However, the prospective cross-lagged effects were estimated while adjusting for a prior measurement of the outcome and this method is vulnerable for spurious findings due to correlations with residuals and regression toward the mean. The present re-analyses of the meta-analytic effects indicated that depending on used model one can choose to claim that social support has either a decreasing, an increasing, or no prospective effect on subsequent change in PTSD symptom severity, and vice versa. Therefore, claims over and above a negative cross-sectional correlation between social support and PTSD, including the social causation and social selection models, can be questioned. The findings were validated by analyses of simulated data, which indicated that prospective effects were not necessary for the observed meta-analytic associations.


3D hypoxia-mimicking and anti-synechia hydrogel enabling promoted neovascularization for renal injury repair and regeneration.
In-situ renal tissue engineering is promising yet challenging for renal injury repair and regeneration due to the highly vascularized structure of renal tissue and complex high-oxidative stress and ischemic microenvironment. Herein, a novel biocompatible 3D porous hydrogel (DFO-gel) with sustained release capacity of hypoxia mimicking micromolecule drug deferoxamine (DFO) was developed for in-situ renal injury repair. In vitro and in vivo experimental results demonstrated that the developed DFO-gels can exert the synchronous benefit of scavenging excess reactive oxygen species (ROS) regulating inflammatory microenvironment and promoting angiogenesis for effective renal injury repair by up-regulating hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The in-situ neogenesis of neonatal glomerular- and tubular-like structures in the implanted areas in the partially nephrectomized rats also suggested the potential for promoting renal injury repair and regeneration. This multifunctional hydrogel can not only exhibit the sustained release and promoted bio-uptake capacity for DFO, but also improve the renal injured microenvironment by alleviating oxidative and inflammatory stress, accelerating neovascularization, and promoting efficient anti-synechia. We believe this work offers a promising strategy for renal injury repair and regeneration.


Oncologic Surgery to the Ciliary Region.
Dermatologic surgery for tumors affecting only the ciliary region is not very common and it can sometimes be difficult to find published descriptions that deal specifically with surgery to this area. However, reconstruction of the ciliary region is very important, not only because this region is necessary to protect the eye, but also because its position and continuity are of great importance in facial expression, aesthetic appearance, and harmony. We present the cases of patients who have undergone oncologic surgery to the eyebrow region in our department in recent years and review the different techniques proposed for reconstruction of this region.


Non-neuromuscular determinants of intraluminal urethral pressure in the female baboon: relative importance of vascular and nonvascular factors.
The female urethral sphincteric mechanism has both neuromuscular and non-neuromuscular components. The latter component has several determinants, including the urethral mucosa, the connective tissue of the urethra and periurethra, and the submucosal vascular bed. This study was designed to characterize the non-neuromuscular component of the urethral pressure profile (UPP) by quantitating the relative contributions of its vascular and non-vascular determinants in four female baboons. Following minimization of the smooth muscle and striated muscle determinants (the neuromuscular component) with halothane and pancuronium bromide, UPPs were performed before and after aortic occlusion. It is concluded that vascular and non-vascular factors contribute nearly equally to the non-neuromuscularly generated portion of intraluminal urethral pressure.


[Representatives of orthopaedic and trauma surgery residents in Germany].
In most German hospitals there are resident representatives to stand in for the rights and interests of residents. The precise number of representatives in orthopaedic and trauma surgery is unknown, as well as the field of duty and the rights of this position.The Junges Forum O&U presents survey data, which were collected from members of the German Society for Trauma Surgery (DGU), the German Society for Orthopaedics and Orthpaedic Surgery (DGOOC) and the German Society for Orthopaedics and Trauma (DGOU). All had an age below 40 years. The Survey was carried out in a period between 27th of January 2015 and 26th of March 2015.These data allowed the Junges Forum O&U to analyse the duties and numbers of representatives for residents in orthopaedic and trauma surgery in Germany. Questionnaires from 316 representatives were fully analysed. Of these, 92 % work at university hospitals. The conditions of election and the duties are not defined. The activity as representative was mainly fulfilled in spare time. The major aspect was conflict resolution between colleagues.The Junge Forum O&U presents the recommendation for election, field of duty and meetings on a regular basis with the other residents or even the first-line management.


Early fluid and protein shifts in men during water immersion.
High precision blood and plasma densitometry was used to measure transvascular fluid shifts during water immersion to the neck. Six men (28-49 years) undertook 30 min of standing immersion in water at 35.0 +/- 0.2 degrees C; immersion was preceded by 30 min control standing in air at 28 +/- 1 degrees C. Blood was sampled from an antecubital catheter for determination of blood density (BD), plasma density (PD), haematocrit (Ht), total plasma protein concentration (PPC), and plasma albumin concentration (PAC). Compared to control, significant decreases (p less than 0.01) in all these measures were observed after 20 min immersion. At 30 min, plasma volume had increased by 11.0 +/- 2.8%; the average density of the fluid shifted from extravascular fluid into the vascular compartment was 1006.3 g.l-1; albumin moved with the fluid and its albumin concentration was about one-third of the plasma protein concentration during early immersion. These calculations are based on the assumption that the F-cell ratio remained unchanged. No changes in erythrocyte water content during immersion were found. Thus, immersion-induced haemodilution is probably accompanied by protein (mainly albumin) augmentation which accompanies the intravascular fluid shift.


Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia-Any Link with Known Prognostic Factors?
Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.


Cardiorenal outcomes by indices of liver steatosis and fibrosis in individuals with type 2 diabetes and atherosclerotic cardiovascular disease: Analyses from VERTIS CV, a randomized trial of the sodium-glucose cotransporter-2 inhibitor ertugliflozin.
To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention-to-treat analysis set). Cardiorenal outcomes (major adverse CV events [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB-4 quartiles (Q1-Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2 , HSI 44.0 and FIB-4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB-4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval [CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 [95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB-4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. In VERTIS CV, higher FIB-4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI.


A possible new morphological variant of mantle cell lymphoma with plasma-cell type Castleman disease-like features.
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by overexpression of cyclin D1 resulting from t(11;14)(q13;q32) translocation. Herein, we report 3 cases of MCL with features of plasma cell-type Castleman disease (CD). The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia. Lymph node biopsy specimens of the 3 cases showed histological features of plasma cell-type CD, including atrophic germinal centers and interfollicular plasmacytosis, with no light chain restriction. However, flow cytometric analysis demonstrated an abnormal B-cell population with CD5 expression, and further analysis using cyclin D1 immunostaining highlighted a neoplastic component that was restricted to the mantle zone. These neoplastic cells were immunohistochemically positive for CD20, CD5, and SOX11, and negative for CD3, CD10, and HHV8. The Ki67 index was low. All patients were finally diagnosed with MCL. This rare type of MCL can be misdiagnosed clinically and histologically as CD. Therefore, it is important to recognize this rare type of MCL, and careful examination is required using both histological and flow cytometric analyses.


The application of rigid internal fixation to the treatment of non-union and delayed union using the AO technique.
This paper describes our experience over a period of 10 years (1966-76) with fractures showing non-union and delayed union. All were treated by the AO technique. The source of our patients, the management of their fractures and the results are described. From this experience we have drawn conclusions on which future policy will be based.


Effects of propafenone on induction and maintenance of atrioventricular nodal reentrant tachycardia.
Electrophysiologic studies were performed in 10 patients with atrioventricular (A-V) nodal reentrant paroxysmal supraventricular tachycardias (PSVT), before and after intravenous administration of propafenone (1.5 mg/kg). All patients utilized an A-V nodal slow pathway for anterograde conduction and an A-V nodal fast pathway for retrograde conduction of the reentrant impulse. Propafenone depressed retrograde fast pathway conduction which was manifested by: 1) complete V-A block at all ventricular paced cycle lengths after propafenone in 3 cases; 2) increase in mean +/- SD of ventricular paced cycle length producing V-A block from less than 308 +/- 37 ms to 432 +/- 63 ms in the remaining 7 patients. Nine of the 10 patients had induction of sustained PSVT before propafenone. In 7 of the 9, PSVT could not be induced or sustained after propafenone, reflecting depression of the retrograde fast pathway conduction with either absence of atrial echoes (5 patients) or induction of nonsustained PSVT, with termination occurring after the QRS (2 patients). In 1 patient, single atrial echoes were induced before propafenone but none were noted after the drug. In only 2 patients was a sustained PSVT inducible after propafenone. In conclusion, propafenone inhibited induction of sustained A-V nodal reentrant PSVT in most patients, reflecting depression of retrograde A-V nodal fast pathway conduction.


Topical Treatment for the Management of Atopic Dermatitis
Atopic dermatitis affects up to 20% of children and continues to increase in prevalence. Effective disease control is aimed at decreasing symptoms and reducing the frequency of flares, which may be complicated by secondary bacterial infections. Although recent advances have produced a number of non-systemic treatment options, topical corticosteroids remain a fundamental component of treatment algorithms. J Drugs Dermatol. 2019;18(2 Suppl):s112-116.


Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids.
Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe(3+) and La(3+) ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program (www.matrixscience.com) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.


Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma.
A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones.


Silicon multi-nanochannel FETs to improve device uniformity/stability and femtomolar detection of insulin in serum.
Here we demonstrate the use of multiple Si nanochannel (NC) or nanograting (NG) instead of the conventional single nanochannel or nanowire design in biosensors. The NG devices can significantly reduce device-to-device variation, and improve device performance, e.g. higher current, higher ON/OFF ratio, smaller subthreshold slope, lower threshold voltage Vt in buffer solution. NG devices also result in higher sensor stability in buffer and diluted human serum. We believe such improvements are due to reduced discrete dopant fluctuation in the Si nanowires and biochemical noise in the solution because of the multiple-channel design. The improved devices allow us to sense pH linearly with 3-aminopropyltriethoxysilane coated devices, and to selectively detect insulin with limit of detection down to 10 fM in both buffer solution and diluted human serum without pre-purification.


Late hematoma after aesthetic breast augmentation with textured silicone prosthesis: a case report.
Late hematoma is an extremely rare complication after augmentation mammaplasty with silicone prostheses. The authors present a case of late hematoma after breast augmentation with textured gel-filled silicone prostheses, which appeared after intense physical effort 1 year after the implantation of the prosthesis. The hematoma was drained in three subsequent ultrasound-guided percutaneous needle aspirations, with no need for removal of the implant. In a 9-month follow-up period, the patient had no other problems with the implants.


Submandibular responses to stimulation of the parasympathetic innervation in bursts in the anaesthetized ferret.
1. Submandibular salivary and vascular responses to different patterns of stimulation of the parasympathetic innervation have been investigated in anaesthetized ferrets in the presence and absence of atropine. 2. At low stimulus frequencies likely to fall within the physiological range (0.5-2.0 Hz continuously; 5.0-20.0 Hz in 1 s bursts at 10 s intervals) secretion of fluid and protein were both potentiated by the bursting pattern of stimulation and the latency of the secretory response was reduced. Over a somewhat lower range (0.5-1.0 Hz continuously; 5.0-10.0 Hz in bursts) the submandibular vascular response was also significantly potentiated by employing this intermittent pattern of stimulation. Above these frequency ranges no such potentiation occurred. 3. Pre-treatment with atropine (2.0 mg kg-1) blocked the submandibular secretory responses to stimulation of the chorda-lingual nerve at these low frequencies and the residual responses at higher frequencies were not significantly affected by changing the pattern of stimulation. The vascular response was somewhat reduced after atropine but that which persisted was enhanced by stimulating in bursts. 4. It is concluded that the release of some transmitter from postganglionic terminals in the submandibular gland of the ferret must be potentiated by the arrival of action potentials at short intervals and possible mechanisms are considered.


Blood glucose self-monitoring in non-insulin-treated type 2 diabetes: a qualitative study of patients' perspectives.
Self-monitoring of blood glucose is controversial in the management of type 2 diabetes. Some research suggests that self-monitoring improves glycaemic control, whereas other research is sceptical about its value for people with type 2 diabetes who are not on insulin. Although blood glucose meters are widely available and used by this group, patients' own views are absent from the debate. To explore the pros and cons of glucose monitoring from the patients' perspectives. Qualitative repeat-interview study. Patients were recruited from 16 general practices and three hospital clinics within four local healthcare cooperatives in Lothian, Scotland. Interview data from 40 patients diagnosed with type 2 diabetes within the previous 6 months were analysed using thematic analysis informed by grounded theory. We report findings from round 1 and round 2 interviews. Glucose monitoring can heighten patients' awareness of the impact of lifestyle; for example, dietary choices, on blood glucose levels. Glucose monitoring amplifies a sense of 'success' or 'failure' about self-management, often resulting in anxiety and self-blame if glucose readings remain consistently high. Moreover, monitoring can negatively effect patients' self-management when readings are counter-intuitive. Our analysis highlights the importance of understanding the meanings that newly diagnosed patients attach to glucose self-monitoring. To maximise the positive effects of self-monitoring, health professionals should ensure that patients understand the purpose of monitoring and should clarify with patients how readings should be interpreted.


Design, Development, and Evaluation of the Blood Collection Management Workstation.
To design and develop a blood collection management workstation with high usability to reduce the risk of preanalytical errors and improve patient safety. A five-phase mobile application development lifecycle model (MADLC) and experience-based co-design (EBCD) were used for design and development. Subsequently, the blood collection management workstation was evaluated using the Chinese System Usability Scale (SUS) in a general ward setting from January to June 2021. It was used on 2593 in-patients who underwent phlebotomy with 12,378 tubes being labeled. The rate of errors and meantime for blood sampling were decreased compared with the same period in the previous year. A total of 14 nurses agreed to participate in the evaluation, and the overall raw SUS score was 69.26 ± 10.39, which indicated above average results. The blood collection management workstation has shown the potential to decrease errors and improve working efficiency in a clinical setting. The study also identified some weaknesses, which will be amended in the future.


Use of Foodomics for Control of Food Processing and Assessing of Food Safety.
Food chain, food safety, and food-processing sectors face new challenges due to globalization of food chain and changes in the modern consumer preferences. In addition, gradually increasing microbial resistance, changes in climate, and human errors in food handling remain a pending barrier for the efficient global food safety management. Consequently, a need for development, validation, and implementation of rapid, sensitive, and accurate methods for assessment of food safety often termed as foodomics methods is required. Even though, the growing role of these high-throughput foodomic methods based on genomic, transcriptomic, proteomic, and metabolomic techniques has yet to be completely acknowledged by the regulatory agencies and bodies. The sensitivity and accuracy of these methods are superior to previously used standard analytical procedures and new methods are suitable to address a number of novel requirements posed by the food production sector and global food market.


Quality of care and the burden of two cultures: when the world of the nurse's aide enters the world of the nursing home.
Using ethnographic data, the two worlds of the nurse's aides were examined, the world in which they live and the world in which they work. Because the institutional culture of the nursing home often adds to the adversity of their personal life, the nurse's aides move between the two milieus in a self-perpetuating negative cycle. Aides carry to the bedside of elderly residents the affective and psychological burden these two worlds place on them.


[Improvements in oral anticoagulant therapy for atrial fibrillation].
For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.


Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency.
Approximately 30% of autogenous vein grafts develop luminal narrowing and fail because of intimal hyperplasia or negative remodeling. We previously found that vein graft cells from patients who later develop stenosis proliferate more in vitro in response to growth factors than cells from patients who maintain patent grafts. To discover novel determinants of vein graft outcome, we have analyzed gene expression profiles of these cells using a systems biology approach to cluster the genes into modules by their coexpression patterns and to correlate the results with growth data from our prior study and with new studies of migration and matrix remodeling. RNA from 4-hour serum- or platelet-derived growth factor (PDGF)-BB-stimulated human saphenous vein cells obtained from the outer vein wall (20 cell lines) was used for microarray analysis of gene expression, followed by weighted gene coexpression network analysis. Cell migration in microchemotaxis chambers in response to PDGF-BB and cell-mediated collagen gel contraction in response to serum were also determined. Gene function was determined using short-interfering RNA to inhibit gene expression before subjecting cells to growth or collagen gel contraction assays. These cells were derived from samples of the vein grafts obtained at surgery, and the long-term fate of these bypass grafts was known. Neither migration nor cell-mediated collagen gel contraction showed a correlation with graft outcome. Although 1188 and 1340 genes were differentially expressed in response to treatment with serum and PDGF, respectively, no single gene was differentially expressed in cells isolated from patients whose grafts stenosed compared with those that remained patent. Network analysis revealed four unique groups of genes, which we term modules, associated with PDGF responses, and 20 unique modules associated with serum responses. The "yellow" and "skyblue" modules, from PDGF and serum analyses, respectively, correlated with later graft stenosis (P = .005 and P = .02, respectively). In response to PDGF, yellow was also associated with increased cell growth. For serum, skyblue was also associated with inhibition of collagen gel contraction. The hub genes for yellow and skyblue (ie, the gene most connected to other genes in the module), scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN), respectively, were tested for effects on proliferation and collagen contraction. Knockdown of SCARA5 increased proliferation by 29.9% ± 7.8% (P < .01), whereas knockdown of SBSN had no effect. Knockdown of SBSN increased collagen gel contraction by 24.2% ± 8.6% (P < .05), whereas knockdown of SCARA5 had no effect. Using weighted gene coexpression network analysis of cultured vein graft cell gene expression, we have discovered two small gene modules, which comprise 42 genes, that are associated with vein graft failure. Further experiments are needed to delineate the venous cells that express these genes in vivo and the roles these genes play in vein graft healing, starting with the module hub genes SCARA5 and SBSN, which have been shown to have modest effects on cell proliferation or collagen gel contraction.


C-terminal domains of Listeria monocytogenes bacteriophage murein hydrolases determine specific recognition and high-affinity binding to bacterial cell wall carbohydrates.
Listeria monocytogenes phage endolysins Ply118 and Ply500 share a unique enzymatic activity and specifically hydrolyse Listeria cells at the completion of virus multiplication in order to release progeny phage. With the aim of determining the molecular basis for the lytic specificity of these enzymes, we have elucidated their domain structure and examined the function of their unrelated and unique C-terminal cell wall binding domains (CBDs). Analysis of deletion mutants showed that both domains are needed for lytic activity. Fusions of CBDs with green fluorescent protein (GFP) demonstrated that the C-terminal 140 amino acids of Ply500 and the C-terminal 182 residues of Ply118 are necessary and sufficient to direct the murein hydrolases to the bacterial cell wall. CBD500 was able to target GFP to the surface of Listeria cells belonging to serovar groups 4, 5 and 6, resulting in an even staining of the entire cell surface. In contrast, the CBD118 hybrid bound to a ligand predominantly present at septal regions and cell poles, but only on cells of serovars 1/2, 3 and 7. Non-covalent binding to surface carbohydrate ligands occurred in a rapid, saturation-dependent manner. We measured 4 x 104 and 8 x 104 binding sites for CBD118 and CBD500 respectively. Surface plasmon resonance analysis revealed unexpected high molecular affinity constants for the CBD-ligand interactions, corresponding to nanomolar affinities. In conclusion, we show that the CBDs are responsible for targeting the phage endolysins to their substrates and function to confer recognition specificity on the proteins. As the CBD sequences contain no repeats and lack all known sequence motifs for anchoring of proteins to the bacterial cell, we conclude that they use unique structural motifs for specific association with the surface of Gram-positive bacteria.


Transient heterosynaptic depression in the hippocampal slice.
Two independent, excitatory, monosynaptic afferent fiber systems projecting onto basal and apical dendritic layers of the CA1 sub-field of the hippocampus were tested for interactive effects. Long-term potentiation of either of the pathways was accompanied by a transient depression in the other pathway. Similar transient depression could be elicited by antidromic stimulation of the CA1 cells. No long-term heterosynaptic effects were observed.


Pyramidal tract imaging in multiple-system atrophy.
A new radiological finding of T2 FLAIR hyperintensities in the pyramidal tracts is described in a patient clinically thought to have idiopathic Parkinson's disease but histologically proven to have multiple-system atrophy.


Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia.
A decrease in serum sodium ion concentration below 135 mmol L-1 is usually accompanied by a decrease in plasma osmolality (hypoosmotic hyponatremia) and leads to the disorder of intracranial homeostasis mainly due to cellular swelling. Recently, using an in vitro model of hypoosmotic hyponatremia, we have found that a decrease in sodium ion concentration in the perfusate to 121 mmol L-1 relaxes the isolated rat middle cerebral artery (MCA). The aim of the present study was to explore the mechanism responsible for this relaxation. Isolated, pressurized, and perfused MCAs placed in a vessel chamber were subjected to a decrease in sodium ion concentration to 121 mmol L-1. Changes in the diameter of the vessels were monitored with a video camera. The removal of the endothelium and inhibition of nitric oxide-dependent signaling or the reverse mode sodium-calcium exchanger (NCX) were used to study the mechanism of the dilation of the vessel during hyponatremia. The dilation of the MCA (19 ± 5%, p < 0.005) in a low-sodium buffer was absent after removal of the endothelium or administration of the inhibitor of the reverse mode of sodium-calcium exchange and was reversed to constriction after the inhibition of nitric oxide (NO)/cGMP signaling. The dilation of the middle cerebral artery of the rat in a 121 mmol L-1 Na+ buffer depends on NO signaling and reverse mode of sodium-calcium exchange. These results suggest that constriction of large cerebral arteries with impaired NO-dependent signaling may be observed in response to hypoosmotic hyponatremia.


Evaluation of resin-bonded retainers with the scanning electron microscope.
The data confirmed that etching produced a stronger bond than air abrasion of the metal.


Selectivity in acquired prosopagnosia: The segregation of divergent and convergent operations.
Face recognition can be viewed as part of a divergent set of operations in object recognition, in which information from common low-level visual mechanisms feeds forward into increasingly specialized processes for different object types. This divergence may also involve hemispheric specialization, notably for faces in the right and words in the left hemisphere. However, in person recognition, face processing is one of a set of sensory inputs that converge upon access to stored information about people. We review the literature and evidence from a cohort of acquired prosopagnosic subjects, on three issues concerning selectivity. First, we review the data on object recognition in prosopagnosia, and recent evidence that, after adjusting for pre-morbid car expertise, impairments of car identification are common in our cohort, particularly among car experts. Second, we review the data on word processing in prosopagnosia. In our cohort we show that the word-length effect in single word reading is normal after right-sided lesions, but the discrimination of font and handwriting is impaired in most of our subjects, regardless of lesion location. Third, we discuss the status of voice recognition in prosopagnosia, and show that in our cohort, right anterior temporal lesions do not impair this function, but bilateral ones do. Together, these findings suggest that the processes for faces, cars and visual text involve either the same neural resources or parallel processes in close proximity. Voice and face processing remain distinct in our subjects, and confirm that right anterior temporal lesions cause an associative prosopagnosia rather than a multi-modal person recognition syndrome.


The amplitude of Mmax in human wrist flexors varies during different muscle contractions despite constant posture.
The amplitude of the maximal direct motor response (Mmax) elicited by supramaximal peripheral nerve stimulation can vary with time and with changes in muscle length. We sought to investigate the variability in the amplitude of Mmax in the human wrist flexors (flexor carpi radialis, FCR) at a constant joint position during different functional tasks. The subjects performed isometric wrist extension, radial deviation and gripping contractions matching either 10% or 50% of the EMG activity recorded in the extensor carpi radialis brevis (ECRB) during a wrist extension maximal voluntary contraction (MVC). Three supramaximal stimuli were delivered to the median nerve near the elbow during each task with 2-3 s between stimuli. Considerable variation was observed in the Mmax amplitude between the six tasks for individual subjects (coefficient of variation (CV) range, 6.0-31.4%). There was significantly greater variability between tasks at 50% MVC than at 10% MVC (p = 0.017). However, there were no systematic differences in Mmax amplitude between the six tasks across the group (p > 0.05). These results suggest that the amplitude of Mmax cannot be assumed as constant during experiments involving voluntary contractions even when subjects maintain the same posture.


New Criteria on Finite-Time Stability of Fractional-Order Hopfield Neural Networks With Time Delays.
In this article, the finite-time stability (FTS) of fractional-order Hopfield neural networks with time delays (FHNNTDs) is studied. A widely used inequality in investigating the stability of the fractional-order neural networks is fractional-order Gronwall inequality related to the Mittag-Leffler function, which cannot be directly used to study the stability of the factional-order neural networks with time delays. In the existing works related to fractional-order Gronwall inequality with time delays, the order was divided into two cases: λ ∈ (0,0.5] and λ ∈ (0.5,+∞) . In this article, a new fractional-order Gronwall integral inequality with time delay and the unified form for all the fractional order is developed, which can be widely applied to investigate FTS of various fractional-order systems with time delays. Based on this new inequality, a new criterion for the FTS of FHNNTDs is derived. Compared with the existing criteria, in which fractional order λ ∈ (0,1) was divided into two cases, λ ∈ (0,0.5] and λ ∈ (0.5,1) , the obtained results in this article are presented in the unified form of fractional order λ ∈ (0,1) and convenient to verify. More importantly, the criteria in this article are less conservative than some existing ones. Finally, two numerical examples are given to demonstrate the validity of the proposed results.


An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission.
Information transfer across CNS synapses depends on the very low basal vesicle fusion rate and the ability to rapidly upregulate that rate upon Ca2+ influx. We show that local electrostatic repulsion participates in creating an energy barrier, which limits spontaneous synaptic transmission. The barrier amplitude is increased by negative charges and decreased by positive charges on the SNARE-complex surface. Strikingly, the effect of charges on the barrier is additive and this extends to evoked transmission, but with a shallower charge dependence. Action potential-driven synaptic release is equivalent to the abrupt addition of ∼35 positive charges to the fusion machine. Within an electrostatic model for triggering, the Ca2+ sensor synaptotagmin-1 contributes ∼18 charges by binding Ca2+, while also modulating the fusion barrier at rest. Thus, the energy barrier for synaptic vesicle fusion has a large electrostatic component, allowing synaptotagmin-1 to act as an electrostatic switch and modulator to trigger vesicle fusion.


Angiogenesis in carotid atherosclerotic lesions is associated with timing of ischemic neurological events and presence of computed tomographic cerebral infarction in the ipsilateral cerebral hemisphere.
We studied the association between plaque vascularity, timing of neurological and ocular symptoms, and presence of cerebral infarction in the ipsilateral cerebral hemisphere on preoperative computed tomographic (CT) scan. Consecutive patients undergoing carotid endarterectomy for carotid stenosis were included. All patients underwent preoperative noncontrast cerebral CT. Histological sections were obtained from carotid endarterectomy specimens and stained with an endothelial cell marker (CD34). Microvessel counts were performed in CD34-stained sections and verified through computerized image analysis. Associations between microvessel density in carotid atherosclerotic plaques, preoperative ipsilateral CT evidence of cerebral infarction, and timing of ipsilateral neurological and ocular events were assessed. Seventy-three patients underwent carotid endarterectomy, of whom 17 were symptomatic within 30 days of carotid endarterectomy, 11 were asymptomatic, and a further 45 had a preoperative symptom-free interval of 31-540 days (median = 56). Eighteen patients (24.6%) had CT evidence of cerebral infarction. Significantly higher microvessel counts were observed in patients with CT evidence of cerebral infarction in the appropriate hemisphere compared with patients who did not (p = 0.02). There was an inverse relationship between the microvessel density in atherosclerotic lesions and the timing of ischemic neurological events (odds ratio [OR] = 4.63, 95% confidence interval [CI] 2.95-7.28, p < 0.001). This relationship was independent of patient age (OR = 1.03, 95% CI 0.55-1.99, p = 0.70), sex (OR = 1.18, 95% CI 0.47-2.05, p = 0.56), smoking (OR = 1.07, 95% CI 0.54-2.09, p = 0.84), diabetes (OR = 0.90, 95% CI 0.45-1.79, p = 0.76), and hypercholesterolemia (OR = 0.98, 95% CI 0.68-1.11, p = 0.88). This study confirms the relationship between angiogenesis in carotid atherosclerotic lesions and development and chronology of ipsilateral hemispheric neurological events.


[The significance of stressful life events and their management in patients with rheumatoid arthritis, essential hypertension and stomach and duodenal ulcer].
In a multivariate approach critical life events and coping in 126 patients with rheumatoid arthritis, hypertension and gastrointestinal ulcers as well as healthy persons are researched with regard to their nosological meaning and their relationship to relevant clinical parameters. They answered a multi-dimensional coping questionnaire and an inventory which measures and evaluates individual relevant life events. With regard to this, different clinical information war processed. On the basis of the above named parameters, the four groups could be distinguished from one another. The interrelationship between psychosocial variables and clinical indices can be neglected.


Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
In the present investigation, two series of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines (2a-l) and thieno[2,3-b]pyridines (3a-l) were designed as analogs of BL 11282 (1). The in vitro glucose dependent insulinotropic activity of all the test compounds was evaluated using RIN5F cell based assay and all the test compounds showed glucose and concentration dependent insulin secretion. The in vivo antidiabetic activities of most potent compounds from each series (2c and 3c) were assessed in C57BL/6J mice. Compounds 2c and 3c showed dose dependent insulin secretion and significant glucose reduction in vivo. In general, compounds 2c and 3c were found to be equipotent at all the three different doses selected and with respect to BL 11282, both the test compounds were found to be more potent, at all the time points.


Changes in myosin heavy chain stoichiometry in pig tracheal smooth muscle during development.
The stoichiometry of the myosin heavy chains (MHCs) has been measured in the tracheal smooth muscle of the pig after electrophoresis on SDS 4% polyacrylamide gel. The ratio of slower migrating MHC to the faster migrating MHC was 2.1 neonates, 1.5 in young and 0.95 in old pigs (P less than 0.01) showing that MHC composition changes with development. The unequal proportion of MHCs was not compatible with a heterodimeric arrangement of the MHCs in the native molecule as proposed earlier by Rovner et al. [(1986) Am. J. Physiol. 250, C861-870] and it is suggested that native molecules may be composed of homodimer heavy chains.


Liver size and indices of drug metabolism in alcoholics.
The role of liver size in drug metabolism was investigated in 34 chronic alcoholics and 28 controls by comparing antipyrine half-life with biopsy content and total amount of hepatic cytochrome P-450 (P-450) and liver weight. Liver size was significantly greater in alcoholics than in controls. Total P-450 was increased and antipyrine metabolism was enhanced in alcoholics with normal histology of the liver. In subjects with alcoholic hepatitis or cirrhosis, the antipyrine half-life was prolonged and P-450 was decreased. Alcoholics with fatty liver had a reduced P-450 content, but the total amount of P-450 and the antipyrine half-life were normal. The results demonstrate in alcoholics that an enlarged liver of normal histological appearance is associated with enhanced drug metabolism. In subjects with fatty liver the drug metabolizing capacity per unit weight of liver is often impaired, but the increase in liver size leads to undisturbed total oxidizing capacity and normal in vivo metabolism. In alcoholic hepatitis drug metabolism is impaired in spite of hepatomegaly. In cirrhosis the enlargement of the liver appears to compensate for the decreased P-450 content resulting in only slightly decreased total P-450, and the severly impaired in vivo drug metabolism may be due to derangement of blood flow.


A corrected double-deflection electron spectrometer equipped with a parallel recording system.
A new type of Electron-Energy-Loss Spectrometer has been designed and built in order to fulfill the requirements for spectroscopic methods and new imaging modes in a STEM. A parallel recording system has been coupled with the spectrometer. The figures of performance were measured and compared to those that had been calculated.


The influence of physicians' specialty on prescribing patterns at a general medicine out-patients clinic.
Several factors have been identified that influence physicians' prescribing habits. The influence of physician's specialty has not been studied. This study is to determine if there are differences in the prescribing patterns amongst these various specialities that run a general medicine clinic at a tertiary hospital in Ghana. Data collected from the out-patients clinic attendance records were analysed using WHO Rational Use of Medicines indicators. Analysis of Variance Test was carried out to establish if there was any variance in the prescribing indicators amongst 4 units of Physicians. 678 patient encounters were utilised for this study. The average number of drugs prescribed per encounter was 4.4, drugs prescribed by generic name was 86.9%, patient encounters in which antibiotics prescribed were 6.5% (n= 44) and injections were prescribed in 3.2% (n=22) of patient encounters. 64.0% of all drugs prescribed were from the Ghanaian EML. The unit of the physician did not have a significant effect on the average number of medicines prescribed per patient encounter (F (3, 674) = 2.19, p = 0.088), and the percentage of medicines that were prescribed from the Essential Medicines List (F (3, 674) = 1.52, p = 0.207). The unit the physician belonged to however did have a significant effect at p < 0.05 on the prescription of generic medications (F (3, 674) = 4.79, p = 0.003). The physician units did not differ in their prescribing patterns at the general medicine clinic except for prescription of drugs by their generic names. None declared.


Investigating years of life lost in Belgium, 2004-2019: A comprehensive analysis using a probabilistic redistribution approach.
Information on years of life lost (YLL) due to premature mortality is instrumental to assess the fatal impact of disease and necessary for the calculation of Belgian disability-adjusted life years (DALYs). This study presents a novel method to reallocate causes of death data. Causes of death data are provided by Statistics Belgium (Statbel). First, the specific ICD-10 codes that define the underlying cause of death are mapped to the GBD cause list. Second, ill-defined deaths (IDDs) are redistributed to specific ICD-10 codes. A four-step probabilistic redistribution was developed to fit the Belgian context: redistribution using predefined ICD codes, redistribution using multiple causes of death data, internal redistribution, and redistribution to all causes. Finally, we used the GBD 2019 reference life table to calculate Standard Expected Years of Life Lost (SEYLL). In Belgium, between 2004 and 2019, IDDs increased from 31 to 34% of all deaths. The majority was redistributed using predefined ICD codes (14-15%), followed by the redistribution using multiple causes of death data (10-12%). The total number of SEYLL decreased from 1.83 to 1.73 million per year. In 2019, the top cause of SEYLL was lung cancer with a share of 8.5%, followed by ischemic heart disease (8.1%) and Alzheimer's disease and other dementias (5.7%). All results are available in an online tool https://burden.sciensano.be/shiny/mortality2019/ . The redistribution process assigned a specific cause of death to all deaths in Belgium, making it possible to investigate the full mortality burden for the first time. A large number of estimates were produced to estimate SEYLL by age, sex, and region for a large number of causes of death and every year between 2004 and 2019. These estimates are important stepping stones for future investigations on Disability-Adjusted Life Years (DALYs) in Belgium.


Clinical neurophysiology in the diagnosis of amyotrophic lateral sclerosis: the Lambert and the El Escorial criteria.
For many years, the only published criteria for the electrodiagnostic (EDX) recognition of amyotrophic lateral sclerosis (ALS) were those formulated by Lambert (1957; 1969). In 1990, different EDX guidelines were incorporated in the all-inclusive diagnostic criteria formulated by a subcommittee on ALS of the World Federation of Neurology, which met in El Escorial, Spain. Unfortunately, particularly in regard to the EDX requirements, the 'El Escorial criteria' have several flaws which compromise their usefulness. These include: (1) they ignore the fact that whenever upper and lower motor neuron disorders co-exist, as they characteristically do with ALS, the motor unit potential firing pattern is controlled by the upper motor neuron lesion; (2) they markedly devalue the usefulness of detecting fasciculations and, through presumably typographical error, state that the 'absence' rather than the 'presence' of fasciculations supports the diagnosis of ALS; this view is in direct conflict with the opinions expressed by most electromyographers; (3) they contain a statement regarding how the diagnosis of ALS is confirmed by the EDX studies which is confusing and, for two of the body regions (bulbar; thoracic), unrealistic; (4) finally, many of the EDX features they listed supporting the recognition of possible LMN degeneration appear to be mislabeled, while a few features in the EDX criteria are incorrect.


The role of nitric oxide in the initiation and in the duration of some vasodilator responses in the coronary circulation.
In the coronary bed vasodilation can be mediated by several mechanisms including endothelium-produced nitric oxide. To examine the contribution of nitric oxide, three different techniques to cause vasodilation in the coronary vessels were used in the anaesthetized dog: intracoronary injection of 1 microgram acetylcholine, sudden reduction of the aortic blood pressure inducing a myogenic response and transient occlusion followed by release of the left circumflex coronary artery causing reactive hyperaemia. Each manoeuvre was performed before and after intracoronary administration of 100 mg N-nitro-L-arginine, an inhibitor of the synthesis of nitric oxide. In contrast to previous investigations, the inhibition of nitric oxide synthesis was prevented from causing an increase in blood pressure by the use of a blood-pressure-compensating device. The results observed during each of the three techniques, suggest that the initial cause of the vasodilatation is not the result of the increase of the production of nitric oxide. However, subsequent to the initiation of vasodilation, an increase in the shear stress can result in an increase in the release of nitric oxide from the vascular endothelium, thus prolonging the vasodilatation obtained using each technique.


Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study.
Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants. In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA. Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66). The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.


What is new in uremic toxicity?
Uremic syndrome results from a malfunctioning of various organ systems due to the retention of compounds which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. One of the more important toxic effects of such compounds is cardio-vascular damage. A convenient classification based on the physico-chemical characteristics affecting the removal of such compounds by dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3) the larger "middle molecules". Recent developments include the identification of several newly detected compounds linked to toxicity or the identification of as yet unidentified toxic effects of known compounds: the dinucleotide polyphosphates, structural variants of angiotensin II, interleukin-18, p-cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by molecules which are "difficult to remove by dialysis". Therefore, dialysis strategies have been adapted by applying membranes with larger pore size (high-flux membranes) and/or convection (on-line hemodiafiltration). The results of recent studies suggest that these strategies have better outcomes, thereby clinically corroborating the importance attributed in bench studies to these "difficult to remove" molecules.


The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs.
Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the depolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent beta-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin.


A biologically active thrombin cleavage product of human serum spreading factor.
Purified human serum spreading factor preparations consisting of two immunologically-related, biologically-active proteins of molecular weights approximately 65,000 and 75,000 were incubated with purified hydrolytic enzymes: papain, neuraminidase and thrombin. Biologically active products of the enzymatic digestions were obtained in each case. Digestion of serum spreading factor preparations with thrombin produced a single active form of molecular weight approximately 57,000. Generation of a single molecular weight form of serum spreading factor by thrombin cleavage of the two higher molecular weight forms should simplify studies of the biochemistry and biology of this protein, and may represent a reaction of physiological significance.


Idiopathic Condylar Resorption: What Should We Do?
Idiopathic condylar resorption (ICR), alternatively called progressive condylar resorption, is an uncommon aggressive form of degenerative disease of the temporomandibular joint seen mostly in adolescent and young women. ICR occurring before the completion of growth results in a shorter mandibular condyloid process, ramus and body, compensatory growth at the gonial angle and coronoid process, as well as an increase in anterior facial vertical dimension. Management options discussed include oral appliances, orthodontics, medical management, orthognathic surgery with and without disc repositioning, and alloplastic temporomandibular joint replacement.


Delayed diagnosis of cystic fibrosis and the family perspective.
The impact of delayed diagnosis of cystic fibrosis (CF) on families is poorly described, especially in the United States. Studies outside the United States indicate that misdiagnosis leads to increased anxiety, guilt, anger, and mistrust of the medical profession, and late diagnosis leads to more negative feelings about the pre-diagnostic period and less confidence in the medical profession. To describe the impact of delayed diagnosis on US families, diagnostic stories were requested on the CF Research, Inc, e-mail list in September 2003. Twenty diagnostic stories were returned, and 20 additional stories were found on the Cystic-L listserv dating back to 1997. Stories were condensed into that of a single family and a qualitative description of the symptoms, medical and family responses at different life stages provided, along with health and family sequelae if the diagnosis had occurred at various ages. Responses to symptoms differed by age. Families were frustrated and stressed by diagnostic incompetence. Ineffectual care led to long-term anxiety, emotional trauma, and self-doubt. Families suffered economic losses. Relationships with one another and with doctors were seriously affected. CF parents consistently expressed that newborn screening would help others avoid the pain they suffered by not knowing the diagnosis earlier.


Messenger RNA chromatographic purification: advances and challenges.
Messenger RNA (mRNA) technologies have shown great potential in prophylactic vaccines and therapeutic medicines due to their adaptability, rapidity, efficacy, and safety. The purity of mRNA determines the efficacy and safety of mRNA drugs. Though chromatographic technologies are currently employed in mRNA purification, they are facing challenges, mainly arising from the large size, relatively simple chemical composition, instability, and high resemblance of by-products to the target mRNA. In this review, we will first make a comprehensive analysis of physiochemical properties differences between mRNA and proteins, then the major challenges facing in mRNA purification and general considerations are highlighted. A detailed summary of the state-of-arts in mRNA chromatographic purification will be provided, which are mainly classified into physicochemical property-based (size, charge, and hydrophobicity) and chemical structure-based (phosphate backbone, bases, cap structure, and poly A tail) technologies. Efforts in eliminating dsRNA byproducts via post in vitro transcript (IVT) purification and by manipulating the IVT process to reduce the generation of dsRNA are highlighted. Finally, a brief summary of the current status of chromatographic purification of the emerging circular mRNA (circRNA) is provided. We hope this review will provide some useful guidance for the Quality by Design (QbD) of mRNA downstream process development.


Trace analysis of dissolved polychlorinated organic compounds in the water of the Yangtse River (Nanjing, China).
Eighteen organochlorine contaminants from the water samples of the Yangtse River have been qualitatively and quantitatively analyzed. The analysis of polychlorinated organic compounds (PCOCs) extracted by C18 Solid Phase Extract (SPE) was performed using HP6890 gas chromatograph coupled by ECD detector. The analytical results demonstrate that the analytical methods are reliable based on the fact that most of the recoveries for the targeted compounds are 60-90%. Most of the concerned contaminants, i.e. chlorinated pesticides and PCBs were found in the water samples of the Yangtse River, but their concentration was very low, <2.97 ng l(-1), which is far less than 1 microg l(-1)--the standard of drinking water of China. It is apparent that the PCOCs were in high concentration during the dry season, and in low concentration during the rainy season. The situation of PCOCs contamination in the water of the Yangtse River in 1999 was greatly improved in comparison with 10 years ago.


The stratum corneum transcriptome in atopic dermatitis can be assessed by tape stripping.
Skin biopsies represent a gold standard in skin immunology and pathology but can cause pain and induce scarring. Non-invasive techniques will facilitate study recruitment of e.g. patients with paediatric atopic dermatitis (AD), hand eczema or facial dermatitis. By RNA sequencing, we examined whether the stratum corneum transcriptome in AD skin can be assessed by tape stripping, as compared to the epidermal transcriptome of AD in skin biopsies. To make the procedure clinically relevant tape strips were stored and shipped at room temperature for up to 3 days. Nine adult Caucasian AD patients and three healthy volunteers were included. Tape samples were collected from non-lesional and lesional skin. Biopsies were collected from lesional skin and were split into epidermis and dermis. Total RNA was extracted, and shotgun sequencing was performed. Shotgun sequencing could be performed on skin cells obtained from two consecutive tape strips which had been stored and shipped at room temperature for up to three days. The most prominent differences between the tape strip and biopsy derived transcriptome were due to structural genes, while established molecular markers of AD, including CCL17, CCL22, IL17A and S100A7-S100A9, were also identified in tape strip samples. Furthermore, the tape strip derived transcriptome showed promise in also analysing the skin microbiome. Our study shows that the stratum corneum (SC) transcriptome of AD can be assessed by tape stripping the skin, supporting that this method may be central in future skin biomarker research. NCBI GEO data accession: GSE160501.


Left anterior minithoracotomy as a first-choice approach for isolated coronary artery bypass grafting and selective combined procedures.
Our goal was to describe the technique for and evaluate the results of the isolated coronary artery bypass grafting or combined grafting procedures with mitral valve repair/replacement and/or left ventricle aneurysm repair performed through a single left anterior minithoracotomy. Perioperative data of all patients who required isolated or combined coronary grafting from July 2017 to December 2021 were observed. The focus was on 560 patients who underwent isolated or combined multivessel coronary bypass using the "Total Coronary Revascularization via left Anterior Thoracotomy" technique. The main perioperative outcomes were analysed. A left anterior minithoracotomy was used in 521 (97.7%) out of 533 patients who required isolated multivessel surgical coronary revascularization and in 39 (32.5%) out of 120 patients who required combined procedures. In 39 patients, multivessel grafting was combined with 25 mitral valve and 22 left ventricular procedures. Mitral valve repair was performed through the aneurysm (n = 8) or through the interatrial septum (n = 17). Perioperative outcomes in isolated and combined groups were next: aortic cross-clamp time-71.9 (SD: 19.9) and 120 (SD: 25.8) min; cardiopulmonary bypass time-145.7 (SD: 33.5) and 216 (SD: 45.8) min; total operating time-269 (SD: 51.8) and 324 (SD: 52.1) min; intensive care unit stay-2 (2-2) and 2 (2-2) days; total hospital stay-6 (5-7) and 6 (5-7) days; and total 30-day mortality was 0.54 and 0%, respectively. A left anterior minithoracotomy can be effectively used as a first-choice approach to perform isolated multivessel coronary grafting and can be combined with mitral valve and/or left ventricular repair. Experience with isolated coronary grafting through an anterior minithoracotomy is required to achieve the satisfactory results in combined procedures.


Enhancement of hydrogen peroxide production by electrochemical reduction of oxygen on carbon nanotubes modified with fluorine.
It is vital to synthesis hydrogen peroxide via electrochemical reduction of oxygen since it is a green process to produce oxidant with wide applications including water/wastewater treatment. In this work, fluorine (F) was employed to modify carbon nanotube (CNT), and the obtained F doped CNT (F-CNT) catalyst was used to fabricate gas diffusion electrode (GDE). It was found that F doping could improve oxygen reduction activity and H2O2 selectivity, and then enhanced the H2O2 production. After modification, F-CNT prepared with 0.6 M HF (CNT-F-0.6) had much higher H2O2 production (47.6 mg L-1) and current efficiency (89.5%) than that of CNT (29.6 mg L-1, 70.1%) at bias voltage of -1.3 V (vs SCE) and pH 7. Moreover, the high catalytic activity of CNT-F-0.6 could maintain in 5 consecutive reaction cycles. The material characterization and electrochemical test indicated that F doping had no significant effects on the surface area of CNT, but improved the defect degree of CNT. The enhanced H2O2 production performance could be ascribed to the formation of CF2 and CF3 on the surface of F-doped CNT, which rendered the potential for practical application of novel carbon catalyst for GDE.


Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.


On the ionic mechanism of cyproheptadine-induced bradycardia in a rabbit sinoatrial node preparation.
The effects of cyproheptadine (0.1-10 microM) on the membrane potentials and currents of rabbit sinoatrial node were examined with the double-microelectrode voltage clamp technique. Cyproheptadine reduced the heart rate, maximum rate of depolarization and action potential amplitude. It also decreased the slope of phase 4 depolarization. On the current systems, cyproheptadine decreased the slow inward current (Isi), the time-dependent potassium outward current (Ik) and the hyperpolarization-activated current (Ih). The reduction of Isi was the major effect. Furthermore, Isi was progressively decreased by repetitive membrane depolarization during administration of cyproheptadine, an effect suggestive of frequency-dependent block of Isi. These electrophysiological observations indicate that cyproheptadine has a calcium antagonistic property, and additionally, decreases Ik and Ih in rabbit sinoatrial node.


[Reactions of normal human and rabbit immunoglobulins with heart valve fibroblasts].
It was demonstrated using the indirect immunofluorescent technique that normal human and rabbit sera, and IgG isolated from them intensively reacted with fibroblasts of human and bovine heart valves. The results obtained with Fab and Fc fragments of IgG sugges that this reaction is due to the Fc region of the IgG molecule and related to the presence of the Fc receptor on fibroblasts of heart valves.


Management of blood pressure in acute stroke.
The importance of elevated or low arterial blood pressure (BP) early after stroke, and the need for pharmacological intervention to control BP, remains controversial. Debate surrounds if, when and how to intervene. This debate is informed by conflicting results from observational data and underpowered clinical trials and substantive outcome data are lacking. Accordingly, management decisions have largely been left up to the individual treating physician and guidelines are based on 'good practice' and theory rather than level 1, grade A evidence. Substantial progress has been made in recent years, particularly in the field of hemorrhagic stroke, where recently presented and soon to completed large-scale trials may finally give us a firm evidence base. For ischemic stroke, many important studies have informed our understanding of the basic pathophysiology, epidemiology, treatment and outcomes of BP management in acute stroke and, although not yet constituting a solid 'evidence base', are helping us from the 'cognitive quick-sand' of small studies and personal experiences.


Efficacy of lentiviral-mediated transfection of hTSHR in poorly differentiated thyroid carcinoma cell line.
Dedifferentiated thyroid cancer is often incurable because it does not respond to radioiodine. This study aimed to investigate iodide uptake and the expressions of thyroid-specific molecules after the transfection of human thyrotropin receptor (hTSHR) gene in poorly differentiated follicular thyroid cancer cell line (FTC-133). pGC-FU-hTSHR-GFP-lentivirus and pGC-FU-GFP-lentivirus were added into FTC-133 cells respectively. The parental cells were defined as the blank group. Cells transduced with pGC-FU-GFP and pGC-FU-hTSHR-GFP were defined as the control group and experimental group respectively. The efficiency of transfection was observed under a fluorescence microscope. (125)I uptake by FTC-133 was analyzed by measuring the radioactivity. Real time-PCR, western blotting and radioimmunoassay were applied to detect the expressions of mRNAs and proteins of Na(+)/I(-) symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) in FTC-133. The green fluorescence was present in 80% of the transduced cells under fluorescence microscope. The iodine uptake of cells transduced with pGC-FU-TSHR-GFP was 3.3 times higher than that in the other two groups (P<0.01). NIS, TSHR, TPO and Tg had been significantly up-regulated in the experimental group as compared to the control group (P<0.01) and the blank group (P<0.01). The hTSHR transfection in FTC-133 improved the expression of thyroid-specific molecules including TSHR, NIS, TPO and Tg and radioiodide uptake.


Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers.
We investigated the feasibility of highly branched cyclic dextrin (HBCD) as an excipient matrix in dry powder inhalers (DPIs). The fine particles of HBCD and HBCD/active pharmaceutical ingredients (APIs) were prepared by spray-drying an ethanol-aqueous solution containing HBCD. The particle size of spray-dried HBCD itself was approximately 3.0μm with a wrinkled shape. Solid-state fluorescence emission spectroscopy of 1-naphthoic acid (1-NPA) showed that it was dispersed in a molecular dispersion/solid solution, if the model compound of 1-NPA was spray-dried with HBCD. Powder X-ray diffraction and differential scanning calorimetry indicate that 1-NPA was in the amorphous state after spray-drying with HBCD, which is confirmed by the fluorescence measurements, 1-NPA could be incorporated into HBCD. When the antimycobacterial agent, rifampicin, was spray-dried with HBCD for the purpose of pulmonary administration, the emitted dose and fine-particle fraction of the spray-dried particles of rifampicin with HBCD were 95.7±1.7% and 39.5±5.7%, respectively. The results indicated that HBCD possessed a high potential as an excipient in DPIs, not only by molecular association of API molecules with HBCD, but also by that of API fine crystals.


Supportive Care: An Indispensable Component of Modern Oncology.
The advent of new cancer therapies, alongside expected growth and ageing of the population, better survival rates and associated costs of care, is uncovering a need to more clearly define and integrate supportive care services across the whole spectrum of the disease. The current focus of cancer care is on initial diagnosis and treatment, and end of life care. The Multinational Association of Supportive Care in Cancer defines supportive care as 'the prevention and management of the adverse effects of cancer and its treatment'. This encompasses the entire cancer journey, and necessitates involvement and integration of most clinical specialties. Optimal supportive care can assist in accurate diagnosis and management, and ultimately improve outcomes. A national strategy to implement supportive care is needed to acknowledge evolving oncology practice, changing disease patterns and the changing patient demographic.


[Use of high-flow oxygen treatment in the emergency medical service: what are the dangers for users from the perspective of occupational and fire protection?]
The administration of high concentrations of oxygen may harm patients or paramedics by increasing the probability of fire. The presented work investigated the effect of oxygen applied via high flow in different concentrations and flow rates on environmental oxygen concentrations in the patient compartment of an ambulance. Environmental oxygen concentrations increased rapidly over time and oxygen is stored in blankets and clothes over a long period. Simulation in a fire laboratory showed that also in high oxygen concentration settings fire needs a flame or temperatures above 300 °C. Sparks alone were not able to start a fire. Ventilation of patient compartment and clothes with ambient air are mandatory to reduce dangerous oxygen concentrations in transport of patients on high-flow oxygen treatment.


Cross Relaxation Channel Tailored Temperature Response in Er3+ -rich Upconversion Nanophosphor.
Recently high doping of lanthanide ions (till 100 %) is realized unprecedentedly in nanostructured upconversion (UC) phosphors. However, oddly enough, this significant breakthrough did not result in a corresponding UC enhancement at ambient temperature, which hinders the otherwise very interesting applications of these materials in various fields. In this work, taking the Er3+ -rich UC nanosystem as an example, we confirm unambiguously that the phonon-assisted cross relaxation (CR) is the culprit. More importantly, combining the theoretical modeling and experiments, the precise roles of different CR channels on UC energy loss are quantitatively revealed. As a result, lowering the temperature can exponentially enhance the relevant UC luminescence by more than two orders of magnitude. Our comprehension will play an important role in promoting the UC performance and further application of high doping rare earth materials. As a proof of concept, an Er3+ -rich core/multi-shell nanophosphor is exploited which demonstrates the great potential of our finding in the field of ultra-sensitive temperature sensing.


[Effect of xinnao shutong capsule on cardiac muscle cell apoptosis and protein expressions of Bcl-2 and Bax in hyperlipidemia rats after myocardial infarction].
To investigate the effect of Xinnao Shutong Capsule, whose main ingredients gross saponins from Tribulus Terrestris L (GSTT) on cardiac muscle cell (CMC) apoptosis and expressions of Bcl-2 Compound rat model of and Bax in murine model of hyperlipemia after myocardial infarction (MI). MI and hyperlipemia was adopted. TUNEL assay was applied to detect CMC apoptosis after 4 weeks' administration of GSTT or simvastatin, and immunohistochemical SP technique was used to detect the expressions of Bcl-2 and Bax protein. GSTT can relieve the damage of CMC and attenuate the ventricular remodeling after MI; high dose of GSTT and simvastatin could decrease CMC apoptosis (P<0.05), and lower Bax protein expression (P < 0.05); and there was no significant difference among the effects in all the treated group (P> 0.05). GSTT can reduce CMC apoptosis through regulating protein expressions of Bcl-2 and Bax, which may be one of the mechanisms of its anti-ventricular-remodeling effects after MI.


Spatial encoding and the single-scan acquisition of high definition MR images in inhomogeneous fields.
We have recently proposed a protocol for retrieving multidimensional magnetic resonance spectra and images within a single scan, based on a spatial encoding of the spin interactions. The spatial selectivity of this encoding process also opens up new possibilities for compensating magnetic field inhomogeneities; not by demanding extreme uniformities from the B(0) fields, but by compensating for their effects at an excitation and/or refocusing level. This potential is hereby discussed and demonstrated in connection with the single-scan acquisition of high-definition multidimensional images. It is shown that in combination with time-dependent gradient and radiofrequency manipulations, the new compensation approach can be used to counteract substantial field inhomogenities at either global or local levels over relatively long periods of time. The new compensation scheme could find uses in areas where heterogeneities in magnetic fields present serious obstacles, including rapid studies in regions near tissue/air interfaces. The principles of the B(0) compensation method are reviewed for one- and higher-dimensional cases, and experimentally demonstrated on a series of 1D and 2D single-scan MRI experiments on simple phantoms.


Adenocarcinoma arising in Barrett's esophagus.
The main goal of this study was to evaluate the development of adenocarcinoma in patients with Barrett's esophagus. During the period from January 1975 to December 1985, a total of 134 patients had endoscopically severe esophagitis and/or Barrett's esophagus. In these patients, 32 (24%) met the macroscopic and histologic criteria for the diagnosis of Barrett's esophagus. A check-up study of these patients was performed in 1987. Adenocarcinoma developed in three patients during the follow-up period of 166.1 patient-years. Dysplasia in the columnar epithelium was found in two of these patients six and 15 months before the diagnosis of adenocarcinoma. The third patient with adenocarcinoma was detected in endoscopic follow-up in 1987. In addition, the endoscopic examination showed unchanged Barrett's epithelium in all but three patients despite the operative and/or medical treatment 3-12 years (mean 6.7 years) earlier. We conclude that Barrett's esophagus is a potential premalignant condition and careful endoscopic surveillance for dysplasia in the columnar epithelium of the distal esophagus is mandatory in patients with Barrett's esophagus.


[Jugulo-carotid glomus and false glomus tumors. Three cases (author's transl)].
A carotid glomus is, classically, a firm, non-pulsatile tumor situated just behind the carotid bifurcation. Erreurs are possible: -- the tumor may be pulsatile, -- the site impossible to define if the tumor is large. Carotid arteriography is essential, in the case of a glomus tumor showing widening of the carotid bifurcation. Treatment is surgical, with possible ablation or reconstruction of the carotid axis. Such surgery must be performed in a specialized centre.


How are large-scale One Health initiatives targeting infectious diseases and antimicrobial resistance evaluated? A scoping review.
While One Health initiatives are gaining in popularity, it is unclear if and how they are evaluated when implementation at scale is intended. The main purpose of this scoping review was to describe how One Health initiatives targeting infectious diseases and antimicrobial resistance at a large scale are evaluated. Secondary objectives included identifying the main facilitators and barriers to the implementation and success of these initiatives, and how their impacts were assessed. Twenty-three studies evaluating One Health initiatives were eligible. Most studies included the human (n = 22) and animal (n = 15) sectors; only four included the environment sector. The types of evaluated initiative (non-exclusive) included governance (n = 5), knowledge (n = 6), protection (n = 17), promotion (n = 16), prevention (n = 9), care (n = 8), advocacy (n = 10) and capacity (n = 10). Studies used normative (n = 4) and evaluative (n = 20) approaches to assess the One Health initiatives, the latter including impact (n = 19), implementation (n = 8), and performance (n = 7) analyses. Structural and economic, social, political, communication and coordination-related factors, as well as ontological factors, were identified as both facilitators and barriers for successful One Health initiatives. These results identified a wide range of evaluation methods and indicators used to demonstrate One Health's added values, strengths, and limitations: the inherent complexity of the One Health approach leads to the use of multiple types of evaluation. The strengths and remaining gaps in the evaluation of such initiative highlight the relevance of comprehensive, mixed-method, context-sensitive evaluation frameworks to inform and support the implementation of One Health initiatives by stakeholders in different governance settings.


The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man.
In inflamed tissues of patients with inflammatory bowel disease (IBD), many immune and non-immune cells produce a vast array of cytokines, which contribute to expand and maintain the pathologic process. Key Message: Interleukin (IL)-12 and IL-23, 2 heterodimeric cytokines sharing the common p40 subunit, are over-produced in IBD and supposed to play a major role in promoting and/or sustaining the pro-inflammatory cytokine response in these disorders. IL-12 targets mostly T cells and innate lymphoid cells and through activation of Stat4 promotes T helper (Th)1 cell polarization, interferon-x03B3; and IL-21 production, while IL-23 activates Stat3 thus amplifying Th17 cell programs. These observations together with the demonstration that IL-12 and IL-23 drive pathogenic responses in animal models of colitis have paved the way for the development of IL-12p40 blockers. Two monoclonal antibodies (ustekinumab and briakinumab) targeting p40 have been tested in Crohn's disease (CD) patients. Blockade of IL-12p40 is beneficial in CD patients resistant to tumor necrosis factor (TNF) antagonists and promotes resolution of psoriatic lesions that develop in IBD patients following anti-TNF therapy. The available human data support the pathogenic role of IL-12/IL-23 in IBD and suggest that IL-12p40 blockers could help manage some subsets of IBD patients.


[Laser in periodontology: theoretical-experimental approach. 2. The laser and biostimulation: hypothesis of the physico-biological mechanism of action].
The Authors describe the physical principles regulating interaction between laser beam and living matter. Then they review the biological assumptions that explain the clinical effects on latest experimental data.


'Desculturización,' urbanization, and nutrition transition among urban Kichwas Indigenous communities residing in the Andes highlands of Ecuador.
The nutrition transition continues to affect populations throughout the world. The added impact of market integration and urbanization exacerbates the impact of the nutrition transition upon Indigenous populations worldwide. This study aims to explore the nutritional concerns of the urban Kichwas community residing in the Andes highlands of Ecuador. This is a qualitative study. Eight focus groups were conducted with Kichwas men and women in November 2015 in the Imbabura province of the Andes in Ecuador. Applied thematic analysis was used to analyze findings regarding nutrition. The participants shared concerns regarding increased intake of fast food, poor meal timing, and a shift in the child's food preferences that rejects traditional foods. They attributed these concerns to urbanization resulting from an increase in dual-income households and a loss of cultural identity. Synergistic cultural factors are related to nutritional concerns voiced by the urban Kichwas community. Syndemic theory is a useful interpretive lens regarding nutritional trends within the Kichwas communities as they relate to the increased risk of chronic disease.


Microhabitat utilization by two leptodactylid frogs in the Andes of central Chile.
Some basic parameters of the life history of Alsodes montanus and Alsodes tumultuosus (Anura-Leptodactylidae), were studied from 1977 to 1980 by periodic field observations at Farellones and La Parva (33-34° south lat.; 2,700-3,000 m above sea level). Special attention was paid to strategies of resource partitioning in relation to gross features of the environment. The latter was unstable with a relative short period favorable for activity of the animals. Physical environmental differences between the first and second season of this study, resulted in a decrease in total number of active adults, a reduction in the duration of larval activity and a shift in microhabitat preferences of larvae.During the favorable season, October to May, adults of both species showed spatial and temporal segregation, related to different physical features of the environment; larvae did not show temporal segregation. Larvae of both species were found in seven different microhabitats; only in one of these did they show significant difference in microhabitat preference, A. tumultuosus was found more often in crevices. Microhabitat dimensions were more important than time and food resources in the separation of the niches of the two species. The segregation of niche dimensions, microhabitat, diel and annual activity and food were not complementary.Coexistence was therefore observed with the species tending to use different resources. When the same resource was used, it was not limiting.