Epithelial damage in nasal polyps.
Bronchial epithelial damage occurs regularly in bronchial asthma, but it is not known whether such damage occurs in the mucosa of nasal polyps. We obtained nasal polyp tissues from thirty patients and we examined these tissues for evidence of epithelial damage. Immediately after resection, polyp tissue was fixed in Karnovsky's fixative, embedded in methacrylate and stained with Giemsa pH 6 X 5. Normal nasal tissue from eight patients undergoing nasal septal reconstruction was similarly processed. As a disease control, we examined tissue from eight patients with nasal polyps associated with cystic fibrosis. Tissues were viewed by microscopy and epithelial damage was expressed as the percent of surface involved. Twenty-eight of the thirty patients with idiopathic nasal polyps (93%) showed complete loss of nasal mucosa in varying degrees (range 3-81% of surface; mean, 29%). All patients showed evidence of some epithelial damage, either complete loss or marked desquamation (range 9-99% of surface; mean 54%). In contrast, six of eight biopsies from patients undergoing septal reconstruction and five of eight nasal polyps from patients with cystic fibrosis showed little or no evidence of epithelial damage. The results indicate that nasal polyps regularly show evidence of epithelial damage similar to that seen in bronchial asthma, and this abnormality may partly explain the rhinorrhea which is prominently associated with nasal polyps.


Giant angioleiomyoma in extremity: report of two cases.
Angioleiomyomas are smooth muscle tumors that occur most often in the extremities and are usually less than 2 cm in diameter. We present 2 case reports of giant angioleiomyoma. Case 1 was a 51-year-old woman with a 5-year history of a slowly growing mass 12x10 cm in diameter in the right posterior thigh. The tumor was larger than any previously reported. Case 2 was a 72-year-old man with an 8-year history of a slowly growing mass 6x6 cm in diameter in the left palm. The tumor was unique in that it grew to a giant size in the hand of the elderly patient. Magnetic resonance imaging of both cases confirmed the tumors' presence in the subcutis. T1-weighted images showed homogenous signal isointense to muscle. On T2-weighted images, areas of hyperintensity and hypointensity intermingled. Three-dimensional gadolinium-enhanced magnetic resonance angiography showed rapid initial enhancement followed by a gradual increase in enhancement, suggesting that the tumors were rich in vessels. Microscopic examination revealed numerous vascular channels embedded within a huge smooth muscle component.


Quality of life and treatment related toxicity in 335 patients with locally advanced cervical carcinoma treated by two chemoradiation regimens.
Concomitant chemoradiotherapy (CT/RT) is the gold standard for advanced cervical carcinoma, but with frequent debates over treatment schedules and toxicity. This study compared 2 concomitant CT/RT regimens in terms of quality of life (QoL) and acute toxicity. Between March 2003 and March 2005, 335 patients with stage IIB-IIIB cervical carcinoma were evaluated in a randomized single-center phase III trial at the Oncology Institute Cluj-Napoca. Patients received concurrent CT/RT with cisplatin 20 mg/m(2), days 1-5, every 21 days (arm A, n=171) or 40 mg/m(2)/weekly (arm B, n=164). QoL was estimated using the EORTC QLQ-30, v.3.0 questionnaire and acute toxicity using the common toxicity criteria (CTC) v.2.0. Significant improvement of global health status (p <0.01) and a decrease in pain (p <0.01) was observed in arm A. In arm B fatigue increased (p=0.01) and role functioning diminished (p=0.05). In both arms depression, nausea, vomiting and diarrhea increased (p <0.05). Gastrointestinal toxicity was similar in both arms (76% vs. 77.5%). Hemoglobin drop was higher in arm B: 75% vs. 63% (p=0.02), while no differences were seen in leukocyte and platelet toxicity. Concomitant CT/RT with cisplatin 20 mg/m(2) x 5 days every 21 days has better impact on patients' QoL and lower toxicity compared with the weekly chemotherapy regimen.


Diversity of Diatrypaceae Species Associated with Dieback of Grapevines in South Africa, with the Description of Eutypa cremea sp. nov.
Recent studies in grape-growing areas including Australia, California, and Spain have revealed an extensive diversity of Diatrypaceae species on grapevines showing dieback symptoms and cankers. However, in South Africa, little is known regarding the diversity of these species in vineyards. The aim of this study was, therefore, to identify and characterize Diatrypaceae species associated with dieback symptoms of grapevine in South Africa. Isolates were collected from dying spurs of grapevines aged 4 to 8 years old, grapevine wood showing wedge-shaped necrosis when cut in cross section as well as from perithecia on dead grapevine wood. The collected isolates were identified based on morphological characters and phylogenetic analyses of the internal transcribed spacer region (ITS) and β-tubulin gene. Seven Diatrypaceae species were identified on grapevine, namely Cryptovalsa ampelina, C. rabenhorstii, Eutypa consobrina, E. lata, E. cremea sp. nov., Eutypella citricola, and E. microtheca. The dying spurs yielded the highest diversity of species when compared with the wedge-shaped necrosis and/or perithecia. C. ampelina was the dominant species in the dying spurs, followed by E. citricola, whereas E. lata was the dominant species isolated from the wedge-shaped necroses and perithecia. These results confirm E. lata as an important grapevine canker pathogen in South Africa, but the frequent association of C. ampelina with spur dieback suggests that this pathogen plays a more prominent role in dieback than previously assumed. In some cases, more than one species were isolated from a single symptom, which suggests that interactions may be occurring leading to decline of grapevines. C. rabenhorstii, E. consobrina, E. citricola, E. microtheca, and E. cremea are reported for the first time on grapevine in South Africa.


[Current status in the commercialization and application of genetically modified plants and their effects on human and livestock health and phytoremediation].
Developments in the use of genetically modified plants for human and livestock health and phytoremediation were surveyed using information retrieved from Entrez PubMed, Chemical Abstracts Service, Google, congress abstracts and proceedings of related scientific societies, scientific journals, etc. Information obtained was classified into 8 categories according to the research objective and the usage of the transgenic plants as 1: nutraceuticals (functional foods), 2: oral vaccines, 3: edible curatives, 4: vaccine antigens, 5: therapeutic antibodies, 6: curatives, 7: diagnostic agents and reagents, and 8: phytoremediation. In total, 405 cases were collected from 2006 to 2010. The numbers of cases were 120 for nutraceuticals, 65 for oral vaccines, 25 for edible curatives, 36 for vaccine antigens, 36 for therapeutic antibodies, 76 for curatives, 15 for diagnostic agents and reagents, and 40 for phytoremediation (sum of each cases was 413 because some reports were related to several categories). Nutraceuticals, oral vaccines and curatives were predominant. The most frequently used edible crop was rice (51 cases), and tomato (28 cases), lettuce (22 cases), potato (18 cases), corn (15 cases) followed.


Biomarker Signatures of Severe Acute Kidney Injury in a Critically Ill Cohort of COVID-19 and Non-COVID-19 Acute Respiratory Illness.
Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined. We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF). Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system. We analyzed 301 patients admitted to an ICU with acute respiratory illness. Outcomes were ascertained between ICU admission and day 14, and included: 1) severe AKI, defined as doubling of serum creatinine or new dialysis and 2) severe ARF, which included new or persistent need for high-flow oxygen or mechanical ventilation. We measured biomarkers of immune response and endothelial function, pathways related to adverse kidney and lung outcomes, in plasma collected within 24 hours of ICU admission. Severe AKI occurred in 48 (16%), severe ARF occurred in 147 (49%), and 40 (13%) patients experienced both. Two-fold higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR-1) (adjusted relative risk [aRR], 1.56; 95% CI, 1.24-1.96) and soluble triggering receptor on myeloid cells-1 (sTREM-1) (aRR, 1.85; 95% CI, 1.42-2.41), biomarkers of innate immune activation, were associated with higher risk for severe AKI after adjustment for age, sex, COVID-19, and Acute Physiology and Chronic Health Evaluation-III. These biomarkers were not significantly associated with severe ARF. Soluble programmed cell death receptor-1 (sPDL-1), a checkpoint pathway molecule, as well as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), molecules involved with endothelial-vascular leukocyte adhesion, were associated with both severe AKI and ARF. sTNFR-1 and sTREM-1 were linked strongly to severe AKI during respiratory illness, while sPDL-1, sICAM-1 and sVCAM-1 were associated with both severe AKI and ARF. These biomarker signatures may shed light on pathophysiology of lung-kidney interactions, and inform precision medicine strategies for identifying patients at high risk for these organ injuries.


Colour tuning by the stepwise synthesis of mononuclear and homo- and hetero-dinuclear platinum(ii) complexes using a zwitterionic quinonoid ligand.
The stepwise reaction of a zwitterionic ligand, 4-methylamino-6-methyliminio-3-oxocyclohexa-1,4-dien-1-olate (QH2) with [Pt2(μ-Cl)2(ppy)2] (Hppy = 2-phenylpyridine) afforded a mononuclear complex, [Pt(ppy)(QH)] (1), and a dinuclear complex, [{Pt(ppy)}2(μ-Q)] (2). Using [Pd2(μ-Cl)2(ppy)2] in the second step resulted in the formation of a heterodinuclear complex, [{Pt(ppy)}(μ-Q){Pd(ppy)}] (3), which is the first heterodinuclear complex bridged by a quinonoid ligand. Single crystal X-ray diffraction analysis revealed that all three complexes adopted double-decker structures in the crystal. For 1, intermolecular N-HO interactions between uncoordinated N-H and O groups in two adjacent square-planar mononuclear units led to the formation of hydrogen-bonded dimers, which stacked to form a herringbone structure with a double-decker tetranuclear motif. For 2 and 3, dinuclear units bridged by Q(2-) formed a double-decker motif similar to that of 1, but a tetranuclear chain in the herringbone pattern was characteristic of the dinuclear complexes. PtPt (or PtPd) distances were more than 3.5 Å, twice the van der Waals radii of Pt, suggesting weak electronic metal-metal interactions in the crystal structures. Thus, the different colours observed (brown, purple, and dark green for 1, 2, and 3, respectively) mainly originated from the molecular structures. In fact, the three complexes exhibited colourful solutions of yellow, red, and green. UV-vis absorption spectroscopy and time-dependent density-functional theory (TD-DFT) calculations revealed that colour variations occurred depending on the electronic states composed of metal ions and the quinonoid ligand.


An Increase of Sigma-1 Receptor in the Penumbra Neuron after Acute Ischemic Stroke.
Penumbra salvage from infarction by early reperfusion within the time window is the target of acute ischemic stroke therapies. Although the penumbral imaging is potently usable in clinic trial, additional work needs to be performed to advancing the field with better-defined, evaluated, and validated imaging measures. Mice were subjected to permanent stroke by right middle cerebral artery (MCA) occlusion. Multimodel magnetic resonance imaging (MRI) method was assessed to define the penumbra as that brain region in which the perfusion and diffusion-weighted MR images are mismatched (perfusion-weighted imaging [PWI]-diffusion-weighted imaging [DWI] mismatch). MRI measurements were performed at 1 hour after MCA occlusion (MCAO). Sigma-1 receptor expression was assessed by immunoblotting and immunostaining in PWI-DWI-defined penumbra and core compared with sham or contralateral slice. Penumbral sigma-1 receptor identified the correlation with the neuron, astrocyte, and microglia by immuno-colocalization. Sigma-1 receptor was significantly upregulated in penumbra or peri-infarct compared with sham and core tissue at 1 hour and 24 hours after MCAO. There was a colocalization of sigma-1 receptor and neuron in penumbra at 1 hour after stroke. Sigma-1 receptor is specifically increased in ischemic penumbral neuron at 1 hour after MCAO. Sigma-1 receptor may act as an endogenous marker of penumbra after acute ischemic stroke.


Determinants of exposure to metalworking fluid aerosol in small machine shops.
The purpose of this study was to evaluate personal exposure to metalworking fluid (MWF) aerosols in very small machine shops (1-8 machinists per shop) and to investigate workplace factors associated with exposures. A total of 20 willing machine shops in Vancouver, Canada (from 46 eligible shops, 43%) and 88 machinists participated (participation rate for machinists 92%). Most machinists wore two personal sampling trains (an open-faced 37 mm cassette and a PM10 impactor) on each of two full work shifts. Observational data were collected regarding potential determinants of exposure at 15 min intervals throughout each shift. A total of 322 personal samples were taken over 54 days. Mean aerosol exposure was 0.32 mg/m3 (range 0.06-2.19) for the 37 mm cassette samples and 0.27 mg/m3 (range 0.026-3.67) for PM10. Exposures from the two sampler types were highly correlated (R = 0.86). The mean shop-specific ratio comparing exposure from the 37 mm cassette with that from the PM10 sampler was 1.43 and varied significantly across shops, ranging from 0.97 to 2.19. Machine, task and shop characteristics associated with significantly increased aerosol exposure included the proportion of time spent grinding, operating an enclosed computer controlled machine, the presence of welding in the shop for both sampler types and the number of machines using MWF for PM10 samples only. Factors associated with reduced aerosol exposure included machining aluminum, milling, the height (and shape) of the shop roof (for both sample types) and the presence of mechanical shop ventilation (for the 37 mm cassette samples).


A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting.
The objective of the study was to compare intranasal fentanyl (INF) with intravenous morphine (IVM) for prehospital analgesia. This was a randomized, controlled, open-label trial. Consecutive adult patients (n = 258) requiring analgesia (Verbal Rating Score [VRS] >2/10 noncardiac or >5/10 cardiac) were recruited. Patients received INF 180 mug +/- 2 doses of 60 mug at > or =5-minute intervals or IVM 2.5 to 5 mg +/- 2 doses of 2.5 to 5 mg at > or =5-minute intervals. The end point was the difference in baseline/destination VRS. Groups were equivalent (P = not significant) for baseline VRS [mean (SD): INF 8.3 (1.7), IVM 8.1 (1.6)] and minutes to destination [mean (SD): INF 27.2 (15.5), IVM 30.6 (19.1)]. Patients had a mean (95% confidence interval) VRS reduction as follows: INF 4.22 (3.74-4.71), IVM 3.57 (3.10-4.03); P = .08. Higher baseline VRS (P < .001), no methoxyflurane use (P < .01), and back pain (P = .02) predicted VRS reduction. Safety and acceptability were comparable. There was no significant difference in the effectiveness of INF and IVM for prehospital analgesia.


Insulin glulisine: efficacy and safety compared with other rapid-acting insulin analogues.
Glulisine insulin is the latest addition to the class of rapid-acting insulin analogues. It is important that it is comparable in safety not only to human regular insulin, but also to the well established analogue insulins, aspart and lispro. In this summary the evidence comparing the safety and efficacy of glulisine with its counterpart insulins in various groups of diabetic patients is discussed.


Single-step real-time PCR to quantify hepatitis B virus and distinguish genotype D from non-D genotypes.
Hepatitis B virus (HBV) viral load and its genotype play important roles in clinical outcome, management of disease and response to antiviral therapy. In many parts of the world such as Europe or the Middle East, distinguishing HBV genotype D from non-D is most relevant for treatment decisions, because genotype D-infected patients respond poorly to interferon-based therapeutic regimens. Here, we developed an in-house real-time PCR to concordantly assess HBV genotype (D vs non-D) based on melt curve analysis and quantify the viral load. Genotype distinction was established with control plasmids of all HBV genotypes and validated with 57 clinical samples from patients infected with six different HBV genotypes. Our in-house real-time PCR assay could discriminate HBV genotype D from non-D using single-step melt curve analysis with a 2 °C difference in the melt curve temperature in all samples tested. Viral load quantification was calibrated with the WHO HBV international standard, demonstrating an excellent correlation with a commercial kit (r = 0.852; P < 0.0001) in a linear range from 3.2 × 10(2) to 3.2 × 10(10) IU/mL. In conclusion, we developed a rapid, simple and cost-effective method to simultaneously quantify and distinguish HBV genotypes D from non-D with a single-step PCR run and melt curve analysis. This assay should be a useful diagnostic alternative to aid clinical decisions about initiation and choice of antiviral therapy, especially in geographical regions with a high prevalence of HBV genotype D.


[Lambda waves in the neonate (author's transl)].
Different types of sharp elements can be observed over the occipital regions from the 2nd postnatal week in the open-eyed child, with active eye movement but practically no body movement. Certain of these sharply localised elements in the occipital midlin are identical to adult lambda waves. Their early occurrence calls to mind the emergence of visual function and attention, these latter occurring at the end of the neonatal period between 7 and 9 days.


Metal-Catalyzed Decarboxylative C-H Functionalization.
C-H bond activation and decarboxylation are two significant processes in organic synthesis. The combination of these processes provides a novel synthetic strategy, that is, decarboxylative C-H bond functionalization. Considerable attention has been focused on such an active research field. This review offers an overview of the utility of decarboxylative C-H bond functionalization in the synthesis of various organic compounds, such as styrenes, chalcones, biaryls, and heterocycles, covering most of the recent advances of the decarboxylative functionalization of Csp-H, Csp2-H, and Csp3-H bonds, as well as their scopes, limitations, practical applications, and synthetic potentials.


[Consensus on diagnostic strategies in connatal dilatations of the urinary tract].
Anomalies of the urinary tract are detected by ultrasound screening in one out of one hundred newborns. In most cases, dilatations of the upper urinary tract result from ureteropelvic junction obstruction or a primary megaureter. Especially in these cases, it is essential to differentiate between an obstruction defined as a stenosis potentially leading to progressive parenchymal damage from a dilatation without any consequences for renal function. The main criteria for assessment of urinary transport are ultrasound examinations to observe the dilatation of the collecting system, washout of the tracer during diuresis renography and lastly split renal function. Standards for investigation procedures are required to ensure comparability of treatment concepts and especially for prospective randomized studies planned for the future. A consensus concerning basic diagnostic strategies has been elaborated by a task force group consisting of members of the "Arbeitsgemeinschaft für Pädiatrische Nephrologie" in cooperation with the "Arbeitskreis Kinderurologie" in the German Society of Urology and the "Kinderurologische Arbeitsgemeinschaft" in the German Society of Pediatric Surgery with advice from leading pediatric radiologists and specialists in pediatric nuclear medicine. The main contents of this consensus are reported.


Symptoms of depression and anxiety in children: specificity of the hopelessness theory.
The common etiology hypothesis proposes that depression and anxiety commonly co-occur because they share etiological factors. This study examined the specificity of the hopelessness theory in the development of depressive and anxious symptoms in children. Students in Grades 3 through 6 (N = 418, 47% boys) completed measures assessing inferential styles about causes, consequences, and the self, depressive symptoms, and anxious symptoms. Six weeks later, children completed measures of depressive symptoms, anxious symptoms, and hassles. All 3 inferential styles interacted with hassles to predict increases in depressive symptoms, although this relation only held for children with low levels of initial symptoms. Inferential styles about consequences and the self also predicted increases in anxious symptoms. Consistent with the common etiology hypothesis, after controlling for the association between depressive and anxious symptoms, the effects of inferential styles about consequences and the self persisted.


Synthesis of Azanucleosides by Anodic Oxidation in a Lithium Perchlorate-Nitroalkane Medium and Diversification at the 4'-Nitrogen Position.
Azanucleosides, in which the 4'-oxygen atom has been replaced with a nitrogen atom, have drawn much attention owing to their anticancer and antivirus activity, and tolerance towards nucleases. However, the traditional synthetic strategy requires multiple steps and harsh conditions, thereby limiting the structural and functional diversity of the products. Herein we describe the synthesis of azanucleosides by an electrochemical reaction in a lithium perchlorate-nitroethane medium, followed by postmodification at the 4'-N position. N-Acryloyl prolinol derivatives were converted into azanucleosides by anodic activation of the N-α-C-H bond. Moreover, the use of nitroethane instead of nitromethane lowered the oxidation potential of the N-acryloyl prolinols and increased the Faradic yield. The prepared azanucleosides were efficiently functionalized at the 4'-N-acryloyl group with a lipophilic alkanethiol and a fluorescent dye by conjugate addition and olefin cross-metathesis, respectively.


[Determination of target compounds in cefoperazone sodium and tazobactam sodium for injection by capillary electrophoresis].
A capillary zone electrophoresis (CZE) method was developed for the simultaneous determination of cefoperazone sodium and tazobactam sodium in the injectable powder of cefoperazone sodium and tazobactam sodium with hydrochlorothiazide as the internal standard. The operation was carried out on a quartz capillary (75 cm x 75 microm i. d. , 63 cm effective length). The electrophoretic conditions were as follows: 40 mmol/L borax solution as the back ground electrolyte (BGE), 12. 0 kV applied voltage, 220 nm as the detection wavelength; the sample solution was injected by hydraulic pressure for 10 s at the height of 10 cm. The cefoperazone and tazobactam showed good linear relationship in the ranges of 0.25-3.96 g/L and 0.062-0.99 g/L with the correlation coefficients of 0.999 5 and 0.999 6, respectively. The relative standard deviations of relative peak areas were less than 3%. The preparation was stable in 208 min. The recovery results met the methodology requirements. The method is simple, rapid, reproducible, and suitable to control the quality of cefoperazone sodium and tazobactam sodium injectable powder.


A practical approach to colic surgery in horses.
Initial treatment of colic is aimed at maintaining hydration and acid-base balance, controlling pain and reestablishing peristalsis. A poor response to medical treatment in the first 12-18 hours suggests the need for laparotomy. Other indications for surgery include: rising pulse rate, exceeding 60/minute for several hours; congested mucosae; delayed capillary refill; silent abdomen; gastric reflux; distended or displaced loops of bowel on rectal examination; intractable pain; and adverse laboratory findings. Postoperative care should consist of hand-walking for 30 days, followed by confinement in a small paddock for another 60 days, and reduced grain intake.


Five year experience in prenatal ultrasound diagnosis of esophageal atresia in Saudi Arabia.
Esophageal atresia (EA), with or without tracheoesophageal fistula (TOF) is one of the most correctable fetal anomalies if diagnosed antenatally by serial ultrasound. We retrospectively evaluated antenatal diagnoses by ultrasound of EA with or without TOF at our institution in Saudi Arabia. We examined the records of mothers and infants with EA with or without TOF who were booked early and delivered at our institution during 1994 to 1998. Fetal diagnosis was based on level II serial ultrasound using a high-resolution ultrasound machine (n=78). In the 5-year period, there were 58 491 live births, with 1345 congenital abnormalities (2.3%) and 78 cases of EA with or without TOF (0.13%) diagnosed antenatally. The survival rate was 68% for women with vaginal deliveries and 60% for women with caesarean deliveries, so caesarean delivery did not improve outcome. The Apgar score was 7 or greater at 5 minutes in 65 cases (83.5%), which emphasizes the problems such patients develop after delivery. Death was caused by anomalies other than EA that were incompatible with life, or in the post-operative period, by septicemia, renal failure or cot death. Our study suggests that early antenatal booking, serial ultrasound and early antenatal diagnosis improves outcome in EA with or without TOF.


Application of extended Kalman filter to identification of enzymatic deactivation.
A recursive estimation scheme, the Extended Kalman Filter (EKF) technique, was applied to study enzymatic deactivation in the enzymatic hydrolysis of pretreated cellulose using a model previously developed by the authors. When no deactivation model was assumed, the results showed no variation with time for all the model parameters except for the maximum rate of cellobiose-to-glucose conversion (r'(m)).The r'(m) variation occurred in two zones with a grace period. A new model of enzymatic hydrolysis of pretreated cellulose deactivation was proposed and validated showing better behavior than the old deactivation model. This approach allows one to study enzyme deactivation without additional experiments and within operational conditions.


Comparison of Psychological, Quality of Life, Work-Limitation, and Socioeconomic Status Between Patients With Occupational Asthma and Work-Exacerbated Asthma.
The aim of this study was to compare psychological status, quality of life (QoL), work limitation, and socioeconomic status between patients with occupational asthma (OA) and work-exacerbated asthma (WEA). The following questionnaires were administered to participants: Beck anxiety and depression (II) inventories, Marks' Asthma Quality of Life Questionnaire, and Work Limitations Questionnaire. Cross-sectional analyses between OA and WEA subgroups were completed. There were 77 participants. WEA subjects had a trend to higher anxiety scores (OA = 9.2 ± 8.0, WEA = 12.8 ± 8.3, P = 0.07, Cohen d = 0.4). Depression scores trended higher for those with WEA (OA = 9.6 ± 10.3, WEA = 13.4 ± 13.5, P = 0.2, Cohen d = 0.3). QoL was comparable between groups. WEA subjects had fewer work limitations (N = 50, OA = 25.1 ± 27.3, WEA = 20.6 ± 24.4, P = 0.56, Cohen d = 0.3) and OA subjects were more likely to have reduced income. In a tertiary clinic, there were some modest differences for specific variables between OA and WEA subjects that may help inform management.


Kondo Impurities in the Kitaev Spin Liquid: Numerical Renormalization Group Solution and Gauge-Flux-Driven Screening.
Kitaev's honeycomb-lattice compass model describes a spin liquid with emergent fractionalized excitations. Here, we study the physics of isolated magnetic impurities coupled to the Kitaev spin-liquid host. We reformulate this Kondo-type problem in terms of a many-state quantum impurity coupled to a multichannel bath of Majorana fermions and present the numerically exact solution using Wilson's numerical renormalization group technique. Quantum phase transitions occur as a function of Kondo coupling and locally applied field. At zero field, the impurity moment is partially screened only when it binds an emergent gauge flux, while otherwise it becomes free at low temperatures. We show how Majorana degrees of freedom determine the fixed-point properties, make contact with Kondo screening in pseudogap Fermi systems, and discuss effects away from the dilute limit.


Usefulness of Blood Cultures and Radiologic Imaging Studies in the Management of Patients with Community-Acquired Acute Pyelonephritis.
The objective of this study was to examine the usefulness of blood cultures and radiologic imaging studies for developing therapeutic strategies in community-acquired acute pyelonephritis (CA-APN) patients. We prospectively collected the clinical data of CA-APN patients who visited 11 hospitals from March 2010 to February 2011. Positive urine and blood cultures were obtained in 69.3% (568/820) and 42.7% (277/648), respectively, of a total of 827 CA-APN patients. Blood culture identified the urinary pathogen in 60 of 645 (9.3%) patients for whom both urine and blood cultures were performed; the organisms isolated from urine were inconsistent with those from blood in 11 and only blood cultures were positive in 49 patients. Final clinical failure was more common in the bacteremic patients than the non-bacteremic ones (8.0% vs. 2.7%, P = 0.003), as was hospital mortality (3.6% vs. 0.3%, P = 0.003). Likewise, durations of hospitalization and fever were significantly longer. Bacteremia was independent risk factor for mortality (OR 9.290, 1.145-75.392, P = 0.037). With regard to radiologic studies, the detection rate of APN was 84.4% (445/527) by abdominal computed tomography and 40% (72/180) by abdominal ultrasonography. Eighty-one of 683 patients (11.9%) were found to have renal abscess, perinephric abscess, urolithiasis, hydronephorosis/hydroureter or emphysematous cystitis, which could potentially impact on clinical management. Patients with Pitt score ≥ 1, flank pain or azotemia were significantly more likely to have such structural abnormalities. Blood cultures are clinically useful for diagnosis of CA-APN, and bacteremia is predictive factor for hospital mortality. Early radiologic imaging studies should be considered for CA-APN patients with Pitt scores ≥1, flank pain or azotemia.


Demonstration of the Maintaining of the Validated State of a System Used to Generate Water for Injection by Thermocompression Distillation.
Water for injection is used in multiple applications in the biopharmaceutical industry. Regarding this, several methods have been use to generate water with this high quality. Within them, the thermocompression distillation method has been widely employed. However, reports on the maintenance of the qualification and validation status of thermocompression systems used for water for injection generation are non-existent in the scientific literature. Therefore, this paper sought to give results of continuous process verification of a system used for water for injection generation over 2 years analyzing the level of conductivity, nitrate, total organic carbon, endotoxins, and microbiology in 1284 water samples. The main findings were that conductivity and nitrate values were always below the specification limit defined according to the United States Pharmacopeia and European Pharmacopoeia, respectively. The highest total organic carbon value measured was 156 ppb. Regarding the microbiology results, the maximum endotoxin content detected was 0.063 EU/mL and 2 cfu/100 mL. In conclusion, this study demonstrated that the analyzed water for injection system operated under a validated status for 2 years, and it was supported by an appropriate monitoring program according to current process validation guidelines.LAY ABSTRACT: There are multiple methods used to produce water for injection in the biopharmaceutical industry. The thermocompression distillation method has been one of the most used methods for the production of this high-quality water. Nevertheless, to verify maintenance of the validated state of these systems it is necessary to carry out continued process verification of different parameters such as conductivity, total organic carbon, limulus amebocyte lysate, and microbiology according to the mandatory requirements of the United States Pharmacopeia and the European Pharmacopoeia. Therefore, this article presents an example of the application of thermocompression technology to generate water for injection and evidence of continuous monitoring to allow demonstration of the efficiency and reliability of these systems used in the biotechnological industry.


Chromatographic investigations of estradiol receptor from breast cancer tissue.
DEAE-cellulose chromatography of non-activated and activated estradiol receptors yields a different, characteristic elution pattern. This chromatography should therefore be able to demonstrate the presence of intact receptors. For clinical receptor investigations, it is usual to select arbitrary cut-off values for receptor quantity and Kd to classify into receptor positive and negative cases. DEAE-cellulose chromatography confirmed the results obtained by such classification in most cases, except those which had been classified as negative on the basis of Kd values higher than 2 nM. In these cases, DEAE-cellulose chromatography indicated the presence of estradiol receptors and therefore a misclassification of the measured results. Thus DEAE-cellulose chromatography can contribute to a clarification of the equivocal results. On the other hand, we did not get any indications of damages to the receptor molecule which in our previous investigations were found to be the result of violent homogenization procedures.


Novel biosensor-based analytic device for the detection of anti-double-stranded DNA antibodies.
Patients with systemic lupus erythematosus (SLE) develop a wide variety of serologic manifestations, including double-stranded DNA autoantibodies (anti-dsDNA). The determination of the potentially pathogenic autoantibodies is diagnostically relevant. We developed a novel surface plasmon resonance (SPR) biosensor chip for studies of dsDNA and anti-dsDNA binding. A synthetic oligonucleotide was coupled to biotinylated human transferrin, hybridized with the complementary antistrand, and ligated with a human recombinant dsDNA fragment 233 bp in length. After surface immobilization of this antigenic construct, diluted sera from SLE patients and healthy donors were analyzed with the resulting SPR biosensor system. This SPR biosensor allowed specific detection of anti-dsDNA. In pilot experiments, sera from SLE patients were distinguished from control sera. We also confirmed the specificity of this biosensor by supplementing anti-dsDNA-positive sera with salmon sperm DNA, which blocked the surface binding of anti-dsDNA in a concentration-dependent manner. An SPR biosensor monitors interactions in real time under homogeneous conditions, providing information about binding kinetics and affinities. Its applicability critically depends on the design of the solid-state surface of the sensor chips. Covalently immobilizing dsDNA as the antigen to the surface in a flow-through cell assured maximal stability for multiple serum injections and regeneration cycles. This technique, which adds a new analytic quality to existing methods, may be beneficial in the diagnosis and clinical monitoring of SLE.


The relationship between preptin, Forkhead box protein O1 and mechanistic target of rapamycin levels in prediabetic patients.
Prediabetes is a state of high risk for developing some metabolic disorders. Previous studies have shown that components of some mediators involved in glucose metabolism regulation may have a profound effect during developing prediabetes state. This study investigates the effect of some novel prediabetic-related factors in prediabetes individuals for the first time. Sixty prediabetes (American Diabetes Association criteria) and 25 healthy control subjects were enrolled in the study. Systemic and chronic inflammatory diseases, coronary heart disease, and malignant disease patients were excluded. Anthropometric measurements and fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, preptin, and serum and leuckocyte levels of FOXO-1 and mTOR were determined. The findings showed an elevated level of leukocyte mTOR in the Impaired Glucose Tolerance (IGT) group and leukocyte FOXO-1 in the Impaired Fasting Glucose (IFG) and IGT groups compared to the control group. Moreover, higher levels of serum, and leukocyte FOXO-1 in the control group, and leukocyte mTOR level in the IFG group were detected in females compared to males. There was a positive correlation between all of the studied serum parameters, and a positive correlation between basal glucose concentration and leukocyte mTOR and FOXO-1. According to our results, elevated serum and cellular levels of mTOR in the IGT group and FOXO-1 in IFG and IGT groups may be triggered by increased glucose concentration. Indeed, mTOR-mediated variations in cellular level from female patients and FOXO-1-mediated variations of male patients indicated that these factors might play a critical role in glucose intolerance.


Expectations of medical specialists about image-based teleconsultation - A qualitative study on acute burns in South Africa.
Image-based teleconsultation between medical experts and healthcare staff at remote emergency centres can improve the diagnosis of conditions which are challenging to assess. One such condition is burns. Knowledge is scarce regarding how medical experts perceive the influence of such teleconsultation on their roles and relations to colleagues at point of care. In this qualitative study, semi-structured interviews were conducted with 15 medical experts to explore their expectations of a newly developed App for burns diagnostics and care prior to its implementation. Purposive sampling included male and female physicians at different stages of their career, employed at different referral hospitals and all potential future tele-experts in remote teleconsultation using the App. Positioning theory was used to analyse the data. The experts are already facing changes in their diagnostic practices due to the informal use of open access applications like WhatsApp. Additional changes are expected when the new App is launched. Four positions of medical experts were identified in situations of diagnostic advice, two related to patient flow-clinical specialist and gatekeeper-and two to point of care staff-educator and mentor. The experts move flexibly between the positions during diagnostic practices with remote colleagues. A new position in relation to previous research on medical roles-the mentor-came to light in this setting. The App is expected to have an important educational impact, streamline the diagnostic process, improve both triage and referrals and be a more secure option for remote diagnosis compared to current practices. Verbal communication is however expected to remain important for certain situations, in particular those related to the mentor position. The quality and security of referrals are expected to be improved through the App but the medical experts see less potential for conveying moral support via the App during remote consultations. Experts' reflections on remote consultations highlight the embedded social and cultural dimensions of implementing new technology.


Effects of stimulation on embryonic activity in the chick.
Effects of stimulation on the stereotyped and coordinated movements in the chick embryo were investigated using the type of stimulation (regular loud clicks) that is known to accelerate development and the time of hatching. The number of coordinated movements, the amount and approximate size of all activity, heart rates and, in 20-day embryos, respiration rates were assessed during a 15-min control period, a 15-min period of stimulation, and a 15-min period of no stimulation. The results showed an increase in the number of coordinated movements, but not their size, and some changes in the heart and respiration rates after the onset of stimulation. These effects occurred in most cases only after several minutes of delay. It is suggested that this delay may be connected with the reciprocal relationship between the coordinated movements and random motility in that the former may be triggered more readily at times when the latter are suppressed.


Endovascular treatment of post-traumatic pseudoaneurysms of ulnar and radial artery.
Aneurysm can develop in all arteries of the human body. Pseudoaneurysm induced by trauma is known as a rare condition in peripheral arteries. This complication is known as late sequelae of trauma. The incidence of pseudoaneurysm in upper extremities artery is less than lower extremities. Atherosclerotic aneurysms are often seen in large arteries and by aging, but pseudoaneurysm can be seen in penetrating or blunt trauma in patients of every age or every location. Delayed treatment of pseudoaneurysm leads to bleeding, venous edema at the extremities and compression on the adjacent nerve as a result of pseudoaneurysm enlargement. Early diagnosis of pseudoaneurysm is very important, because this complication can induce disabilities such as upper extremities and finger loss. Peripheral arteries pseudoaneurysm in distal locations especially in brachial artery and forearm can cause a thrombotic complication in hands and fingers.


Role of Bmznf-2, a Bombyx mori CCCH zinc finger gene, in masculinisation and differential splicing of Bmtra-2.
Deciphering the regulatory factors involved in Bombyx mori sex determination has been a puzzle, challenging researchers for nearly a century now. The pre-mRNA of B. mori doublesex (Bmdsx), a master regulator gene of sexual differentiation, is differentially spliced, producing Bmdsxm and Bmdsxf transcripts in males and females respectively. The putative proteins encoded by these differential transcripts orchestrate antagonistic functions, which lead to sexual differentiation. A recent study in B. mori illustrated the role of a W-derived fem piRNA in conferring femaleness. In females, the fem piRNA was shown to suppress the activity of a Z-linked CCCH type zinc finger (znf) gene, Masculiniser (masc), which indirectly promotes the Bmdsxm type of splicing. In this study, we report a novel autosomal (Chr 25) CCCH type znf motif encoding gene Bmznf-2 as one of the potential factors in the Bmdsx sex specific differential splicing, and we also provide insights into its role in the alternative splicing of Bmtra2 by using ovary derived BmN cells. Over-expression of Bmznf-2 induced Bmdsxm type of splicing (masculinisation) with a correspondingly reduced expression of Bmdsxf type isoform in BmN cells. Further, the site-directed mutational studies targeting the tandem CCCH znf motifs revealed their indispensability in the observed phenotype of masculinisation. Additionally, the dual luciferase assays in BmN cells using 5' UTR region of the Bmznf-2 strongly implied the existence of a translational repression over this gene. From these findings, we propose Bmznf-2 to be one of the potential factors of masculinisation similar to Masc. From the growing number of Bmdsx splicing regulators, we assume that the sex determination cascade of B. mori is quite intricate in nature; hence, it has to be further investigated for its comprehensive understanding.


Diversity and spatial distribution of sediment ammonia-oxidizing crenarchaeota in response to estuarine and environmental gradients in the Changjiang Estuary and East China Sea.
Ammonia-oxidizing archaea (AOA) have recently been found to be potentially important in nitrogen cycling in a variety of environments, such as terrestrial soils, wastewater treatment reactors, marine waters and sediments, and especially in estuaries, where high input of anthropogenic nitrogen is often experienced. The sedimentary AOA diversity, community structure and spatial distribution in the Changjiang Estuary and the adjacent East China Sea were studied. Multivariate statistical analysis indicated that the archaeal amoA genotype communities could be clustered according to sampling transects, and the station located in an estuarine mixing zone harboured a distinct AOA community. The distribution of AOA communities correlated significantly with the gradients of surface-water salinity and sediment sorting coefficient. The spatial distribution of putative soil-related AOA in certain sampling stations indicated a strong impact of the Changjiang freshwater discharge on the marine benthic microbial ecosystem. Besides freshwater, nutrients, organic matter and suspended particles, the Changjiang Diluted Water might also contribute to the transport of terrestrial archaea into the seawater and sediments along its flow path.


Cell research with physically modified microfluidic channels: a review.
An overview of the use of physically modified microfluidic channels towards cell research is presented. The physical modification can be realized either by combining embedded physical micro/nanostructures or a topographically patterned substrate at the micro- or nanoscale inside a channel. After a brief description of the background and the importance of the physically modified microfluidic system, various fabrication methods are described based on the materials and geometries of physical structures and channels. Of many operational principles for microfluidics (electrical, magnetic, optical, mechanical, and so on), this review primarily focuses on mechanical operation principles aided by structural modification of the channels. The mechanical forces are classified into (i) hydrodynamic, (ii) gravitational, (iii) capillary, (iv) wetting, and (v) adhesion forces. Throughout this review, we will specify examples where necessary and provide trends and future directions in the field.


Colony structure and parentage in wild colonies of co-operatively breeding Damaraland mole-rats suggest incest avoidance alone may not maintain reproductive skew.
Colonies of co-operatively breeding African mole-rats have traditionally been thought to be composed of a single breeding female, one or two breeding males, and their offspring. In the naked mole-rat (Heterocephalus glaber), the occurrence of facultative inbreeding means incest avoidance cannot prevent reproduction in subordinate group members, and physiological suppression of reproductive function by the breeding female occurs in both sexes. In contrast, previous studies of captive colonies of the Damaraland mole-rat (Cryptomys damarensis) suggest that breeding within a colony is restricted to a single breeding pair, simply because all other colony members are highly related (first- or second-order relatives) and this species is an obligate outbreeder. Using microsatellite markers, we investigated parentage and colony composition in 18 wild Damaraland mole-rat colonies to determine whether inbreeding avoidance alone can explain the high levels of reproductive skew in this species. Multiple and unidentified paternity was widespread within colonies and immigrants of both sexes were regularly identified. Unrelated, opposite-sex nonbreeders were found coexisting in two colonies. These results suggest that, in the wild, conditions exist where nonreproductive females can come into contact with unrelated males, even when they do not disperse from their natal colony. Inbreeding avoidance alone is therefore insufficient to maintain the high levels of reproductive skew identified in this species suggesting that the breeding female somehow suppresses the reproductive function in nonbreeding females.


Malignant oesophageal strictures: a review of techniques for palliative intubation.
A review of the different designs for palliative oesophageal intubation tubes confirms Souttar's original suggestion that they should be flexible, incompressible, non-traumatic, compact, have an adequate lumen and stay in place. The internal diameter should be at least 10 mm. The thickness of the wall should be about 1 mm. The length will vary according to the stricture and should be as short as possible, provided that the proximal rim prevents future longitudinal growth occluding the lumen. Various methods of achieving the ability to stay in place are described, which comprise either a large proximal rim or a roughened barrel. No details about results are given because the original patient populations vary so much. Success probably depends more on the technical expertise and experience of the surgeon than specific variations in design.


Partial characterization of protease(s) in human breast cancer cytosols that can degrade estrogen and progesterone receptors selectively.
Proteolytic activity in human breast cancer cytosols was studied using hormone receptors from rats as the substrates. Under the conditions tested, limited proteolysis of both the estrogen and the progesterone receptors in uterine cytosol was observed, but not proteolysis of the glucocorticoid or androgen receptors in liver or prostate cytosols, respectively. Although both the nonactivated and activated uterine estrogen receptors were attacked by the enzyme(s), molybdate-stabilized receptors were resistant to proteolysis. The product of estrogen receptor cleavage sedimented at approximately 4S in low-salt gradients and at 3 to 4S in high-salt gradients. This fragment retained both the steroid-binding and DNA-binding domains. The marked decrease in its DNA-binding ability, compared with the salt-dissociated but non-proteolyzed receptors, may be attributable to interactions of the fragment with dialyzable modulator(s) in cytosol. The proteolytic activity in tumor cytosol was leupeptin sensitive and was precipitated by (NH4)2SO4 at 30 to 60% saturation. Its sedimentation coefficient was 4 to 5S. The proteolytic activity was identified in 70% of estrogen receptor-negative tumors but in only 40% of estrogen receptor-positive tumors.


Signaling by estrogens.
By regulating activities and expression levels of key signaling molecules, estrogens control mechanisms that are responsible for crucial cellular functions. Ligand binding to estrogen receptor (ER) leads to conformational changes that regulate the receptor activity, its interaction with other proteins and DNA. In the cytoplasm, receptor interactions with kinases and scaffolding molecules regulate cell signaling cascades (extranuclear/nongenomic action). In the nucleus, estrogens control a repertoire of coregulators and other auxiliary proteins that are associated with ER, which in turn determines the nature of regulated genes and level of their expression (genomic action). The combination of genomic and nongenomic actions of estrogens ultimately confers the cell-type and tissue-type selectivity. Recent studies have revealed some important new insights into the molecular mechanisms underlying ER action, which may help to explain the functional basis of existing selective ER modulators (SERMs) and provide evidence into how ER might be selectively targeted to achieve specific therapeutic goals. In this review, we will summarize some new molecular details that relate to estrogen signaling. We will also discuss some new strategies that may potentially lead to the development of functionally selective ER modulators that can separate between the beneficial, prodifferentiative effects in bone, the cardiovascular system and the CNS as well as the "detrimental," proliferative effects in reproductive tissues and organs.


National Institutes of Health Stroke Scale in Plain English Is Reliable for Novice Nurse Users with Minimal Training.
The National Institutes of Health Stroke Scale (NIHSS) is commonly used in Comprehensive Stroke Centers, but it has not been easily implemented in smaller centers. The aim of this study was to assess whether nurse providers who were naive to stroke assessment scales could obtain accurate stroke severity scores using our previously validated NIH Stroke Scale in Plain English (NIHSS-PE) with minimal or no training. We randomly assigned 122 nursing students who were naive to stroke assessment scales to 1 of 4 groups: trained on the NIHSS, untrained on the NIHSS, trained on the NIHSS-PE, or untrained on the NIHSS-PE. The Trained/NIHSS and Trained/NIHSS-PE groups watched assessment scale-specific training DVDs. All 4 study groups scored the same 3 patients from the National Institute of Neurological Disorders and Stroke certification DVD, in randomly assigned order. Two-way repeated measures analysis of variance was used to compare group scores with those obtained by a consensus panel of NIHSS-certified expert users, and with each other. NIHSS-PE users had scores significantly closer to the expert scores compared with NIHSS users (F(1,118) = 4.656, P = .033). Trained users had scores significantly closer to the expert scores than untrained users (F(1,118) = 6.607, P = .011). Scores from untrained users of the NIHSS-PE did not differ from those of trained users of the NIHSS (F(1,59) = 0.08, P = .780). With minimal or no training, novice nurse users of the NIHSS-PE can do as well as, if not better than, novice users of the NIHSS, making this tool useful for facilities pursuing Acute Stroke-Ready certification.


Diagnostic accuracy of high-resolution neck ultrasonography in the follow-up of differentiated thyroid cancer: a prospective study.
To conduct a prospective study of the diagnostic value of features of cervical lymph nodes (large size, central location, abnormal shape, cystic changes, calcifications, and loss of echogenic hilum), assessed by neck ultrasonography (US), in patients scheduled for surgical treatment of persistent or recurrent differentiated thyroid cancer. We studied 152 US abnormalities in 42 patients (median age, 38.5 years) who had undergone one or more neck operations, with or without radioiodine therapy, but continued to have persistent or recurrent disease, which was confirmed by fine-needle aspiration. Another surgical procedure was planned for these patients. On the day of operation, patients underwent a detailed US neck examination by an experienced radiologist. US abnormalities were plotted on a standard diagram of the neck and given specific numbers to help track them during surgical intervention and histopathologic examinations. The US features were compared with the final histopathologic diagnosis. Of 152 US abnormalities, 127 involved cervical lymph nodes and 25 involved other types of tissue. In univariate analysis, size, absent echogenic hilum, cystic changes, calcifications, and central location (medial to the sternomastoid muscle) of cervical lymph nodes were significantly associated with the presence of metastatic involvement. In multivariate analysis, only central location (odds ratio, 4.07; 95% confidence interval [CI], 1.64 to 10.10) and size (odds ratio, 5.14; 95% CI, 1.64 to 16.06) remained significant. The receiver operating characteristic curve for the size of lymph nodes showed a large area under the curve of 0.77 (95% CI, 0.68 to 0.85), and a size of 7.5 mm showed the highest sensitivity and specificity. Size and central location of cervical lymph nodes assessed by US during follow-up of patients with differentiated thyroid cancer were the most important predictors of presence of metastatic disease.


The ACTH challenge and its repeatability in fattening bulls-influences of physiological state, challenge time standardization, and horn status.
Adrenocorticotropic hormone (ACTH) challenges are frequently performed in repetition when evaluating stress or welfare in animals. To our knowledge, the repeatability of ACTH challenges in cattle, although fundamental to further studies of this type, has not yet been the subject of research. Therefore, the objective of this study was to evaluate the repeatability of ACTH challenges in fattening bulls of different horn status. Eight-one bulls were subjected to 3 consecutive ACTH challenges. The first challenge (C1) was performed in calves aged 1.5 mo. Subsequently, animals were characterized as high or low cortisol responders and either disbudded or left with horns. They were then assigned to 1 of 3 rearing groups: a horned group (H+), a disbudded group (H-), and a mixed group (M; 50% horned and 50% disbudded), with each group containing an equal number of high and low responders. The second ACTH challenge (C2) was performed at the age of 11 mo. Time of day (TOD) of challenge was either fixed (ST = same TOD) or alternated (AT = alternate TOD) between C1 and C2. The third ACTH challenge (C3) was performed 7 d after and at the same TOD as C2. Saliva samples were taken 60 and 30 min before and 30, 60, 90, 120, and 150 min after each intravenous ACTH injection. The area under the curve (AUC) was calculated with respect to both ground (AUCG) and to increase (AUCI). The AUCI increased markedly between C1 and C2 (P < 0.05) in ST bulls, and no effects were observed for AUCG between C1 and C2 in ST or AT bulls, nor for any AUC between C2 and C3 (P > 0.1). The overall repeatability of AUCG and AUCI between C1 and C2, reflecting the repeatability between 2 different physiological states, was poor and moderate, respectively, for ST bulls (AUCG: r = 0.24, P > 0.1, intraclass correlation coefficient (ICC) = 0.21; AUCI: r = 0.48, P < 0.01, ICC = 0.41) and lacked in AT bulls (AUCG: r = 0.07, P > 0.1; ICC = 0.03; AUCI: r = 0.08, P > 0.1, ICC = 0.06). The repeatability of AUCG and AUCI between C2 and C3, reflecting the repeatability within the same physiological state, was moderate (AUCG: r = 0.59, P < 0.001; ICC = 0.53; AUCI: r = 0.58, P < 0.001, ICC = 0.52). Assignment to high and low responder groups based on peak cortisol concentration in C1 did not persist over time. H+ bulls showed higher AUCI in C2 and C3 (P < 0.1 and P < 0.05, respectively) than H- bulls. The M group differed from the H- group only in C3 (P < 0.05). Thus, the effect of horn status on ACTH challenges needs further investigation. In conclusion, our results report poor repeatability of the cortisol response to ACTH challenges for challenges performed in different physiological states and moderate repeatability for challenges performed within the same physiological state. Moreover, they point out the importance of standardization of TOD when performing repeated ACTH challenge.


Mekong at the Crossroads.
The Mekong region is undergoing rapid transitions, socially, economically, and environmentally. Economies are stabilizing after the political turbulence of the last several decades, and development pressures as well as ambitions are vast. Water is related to these social, economic, and environmental changes in many ways and in a very profound manner. This article summarizes the approach and major conclusions of the research project title "Integrated Water Resources Management (IWRM) on the Mekong River." The concept of IWRM is elaborated in the setting of these major transitions, and the roles of academic research and education are highlighted.


T cell clones restricted to "hybrid" HLA-D antigens?
The genetics of T lymphocyte/accessory cell interactions were studied by using antigen-specific monoclonal T cell lines from human peripheral blood and X-irradiated non-T cells (E rosette-depleted) as accessory cells. The T cell lines were obtained by expanding single colonies from soft agar-cloned E rosette-positive lymphocytes, previously incubated for 3 days in liquid culture with 30% autologous X-irradiated non-T cells and antigen (PPD). When investigated with both autologous and allogeneic accessory cells of various HLA-D genotype, different sets of PPD-specific T cell lines were obtained from HLA-D heterozygous individuals; two sets restricted to each one of the two HLA-D antigens, and a third set responding to PPD only when presented by accessory cells carrying both HLA-D antigens possessed by the T cell donor. A few cell lines responded to PPD only in the presence of autologous accessory cells.


The historical demography of a proper Hungarian village: Atány in the eighteenth and nineteenth centuries.
Atány is the first village in the Great Plain region in Hungary to be analyzed by means [of] family reconstitution. Therefore it might be considered a "typical" Hungarian village inhabited by "proper peasants" (Fél and Hofer 1969). Mortality did not improve until the end of the nineteenth century. The age at first marriage for women was slightly above twenty years, and very few women remained single until the end of their reproductive ages. Fertility remained high until the end of the nineteenth century. The development of fertility was very different from the southern Transdanubian villages characterized by early birth control. Nearly half the households had complicated structure, falling between the middle European, Mediterranean, and Eastern household types. These characteristics might be explained by the relative abundance of land in the Great Plain region.


[Vertical condylar hyperplasia, clinical and histologic aspects. Apropos of 2 cases].
Condylar hyperplasia is a pathologic condition associated with an overgrowing of the condylar cartilage. It is possible to distinguish two clinical forms; vertical and horizontal when the lesion is unilateral. We have reported two cases of vertical condylar hyperplasia, both of them treated by simple condylectomy, in our opinion the selected treatment. Histopathological images show an increase of the growth and maturation layers of the condylar cartilage and inclusions of cartilaginous tissue, with appearance of glove fingers into the underlying cancellous bone.


Large conformational changes in the Escherichia coli tryptophan synthase beta(2) subunit upon pyridoxal 5'-phosphate binding.
To understand the basis for the lower activity of the tryptophan synthase beta(2) subunit in comparison to the alpha(2)beta(2) complex, we determined the crystal structures of apo-beta(2) and holo-beta(2) from Escherichia coli at 3.0 and 2.9 A resolutions, respectively. To our knowledge, this is the first report of both beta(2) subunit structures with and without pyridoxal-5'-phosphate. The apo-type molecule retained a dimeric form in solution, as in the case of the holo-beta(2) subunit. The subunit structures of both the apo-beta(2) and the holo-beta(2) forms consisted of two domains, namely the N domain and the C domain. Although there were significant structural differences between the apo- and holo-structures, they could be easily superimposed with a 22 degrees rigid body rotation of the C domain. The pyridoxal-5'-phosphate-bound holo-form had multiple interactions between the two domains and a long loop (residues 260-310), which were missing in the apo-form. Comparison of the structures of holo-Ecbeta(2) and Stbeta(2) in the alpha(2)beta(2) complex from Salmonella typhimurium (Stalpha(2)beta(2)) identified the cause of the lower enzymatic activity of holo-Ecbeta(2) in comparison with Stalpha(2)beta(2). The substrate (indole) gate residues, Tyr279 and Phe280, block entry of the substrate into the beta(2) subunit, although the indole can directly access the active site as a result of a wider cleft between the N and C domains in the holo-Ecbeta(2) subunit. In addition, the structure around betaAsp305 of the holo-Ecbeta(2) subunit was similar to the open state of Stalpha(2)beta(2) with low activity, resulting in lower activity of holo-Ecbeta(2).


Nitric oxide, angiotensin II, and hypertension.
Although initially adaptive, the changes that accompany hypertension, namely, cell growth, endothelial dysfunction, and extracellular matrix deposition, eventually can become maladaptive and lead to end-organ disease such as heart failure, coronary artery disease, and renal failure. A functional imbalance between angiotensin II (Ang II) and nitric oxide (NO) plays an important pathogenetic role in hypertensive end-organ injury. NO, an endogenous vasodilator, inhibitor of vascular smooth muscle and mesangial cell growth, and natriuretic agent, is synthesized in the endothelium by a constitutive NO synthase. NO antagonizes the effects of Ang II on vascular tone, cell growth, and renal sodium excretion, and also down-regulates the synthesis of angiotensin-converting enzyme (ACE) and Ang II type 1 receptors. On the other hand, Ang II decreases NO bioavailability by promoting oxidative stress. A better understanding of the pathophysiologic mechanisms involved in hypertensive end-organ damage may aid in identifying markers of cardiovascular susceptibility to injury and in developing therapeutic interventions. We propose that those antihypertensive agents that lower blood pressure and concomitantly restore the homeostatic balance of vasoactive agents such as Ang II and NO within the vessel wall would be more effective in preventing or arresting end-organ disease.


The validity of the biological eligibility criteria to antiretroviral treatment in comparison to the systematic antiretroviral treatment in a cohort of people living with the HIV in the Southern Kivu Province, Democratic Republic of the Congo.
The late screening of the majority of patients in sub Saharan region would justify a systematic antiretroviral treatment without breaking the country programs vision. he objective of this study was to determine the validity of biological eligibility criteria to antiretroviral treatment compared with systematic antiretroviral treatment in a cohort of the people living with HIV in Bukavu city. One thousand hundred and forty-nine (1149) records of people living with HIV (PLWIV) followed in three HIV health care facilities of Bukavu city were selected systematically. The ROC curve was constructed and analyzed to assess the validity of systematic antiretroviral therapy and a treatment based on WHO biological criteria. The CD4 median count was 196 /mm3. On admission, only 17.3% of PLWHIV had a CD4≥500/mm3. Compared to the criteria "systematic antiretroviral treatment", biological eligibility criteria for antiretroviral therapy, had a sensitivity of 94.9%, a specificity of 100%, an AUC of 0.97 (0.96 to 0.98) (p <0.0001) and correlation coefficient of 0.88. This study shows that a systematic antiretroviral treatment of seropositive patients newly detected for the HIV in sub-Saharan Africa area must be requirement outwards WHO current recommendations. Also, in order to optimize expected outcome of a systematic treatment, a systematic screening in the high-risk groups of this area should be recommended.


Acidic stress induces the formation of P-bodies, but not stress granules, with mild attenuation of bulk translation in Saccharomyces cerevisiae.
The stress response of eukaryotic cells often causes an attenuation of bulk translation activity and the accumulation of non-translating mRNAs into cytoplasmic mRNP (messenger ribonucleoprotein) granules termed cytoplasmic P-bodies (processing bodies) and SGs (stress granules). We examined effects of acidic stress on the formation of mRNP granules compared with other forms of stress such as glucose deprivation and a high Ca²⁺ level in Saccharomyces cerevisiae. Treatment with lactic acid clearly caused the formation of P-bodies, but not SGs, and also caused an attenuation of translation initiation, albeit to a lesser extent than glucose depletion. P-body formation was also induced by hydrochloric acid and sulfuric acid. However, lactic acid in SD (synthetic dextrose) medium with a pH greater than 3.0, propionic acid and acetic acid did not induce P-body formation. The results of the present study suggest that the assembly of yeast P-bodies can be induced by external conditions with a low pH and the threshold was around pH 2.5. The P-body formation upon acidic stress required Scd6 (suppressor of clathrin deficiency 6), a component of P-bodies, indicating that P-bodies induced by acidic stress have rules of assembly different from those induced by glucose deprivation or high Ca²⁺ levels.


A prospective cohort study on the role of nonspecialist staff in preventing relapses and improving clinic attendance of patients with schizophrenia.
The Sri Lankan government employs graduates from local universities (trained in nonpsychiatry disciplines) as Mental Health Development Officers (MHDOs) to fulfill the role of a psychiatric social worker. This was a prospective interventional cohort study on preventing relapses of schizophrenia by active involvement of MHDOs. The intervention (randomly selected) and control groups each had 25 follow-up patients with schizophrenia (1:1 match for sex, ethnicity, age, and duration of illness). The intervention was to develop a close liaison with the patient/family and build an individualized client oriented follow-up through the MHDOs. The follow-up period was 1 year. The intervention group had better clinic attendance, less relapses, and defaults. The number needed to follow-up to avert a relapse or a default was 12.5 and 5 respectively. Low-cost strategies involving nonspecialist staff can reduce relapses and defaults in patients with schizophrenia.


Recognition and management of dissecting aneurysms of the aorta.
The current approach to treatment at St. Mary's Hospital of dissecting aortic aneurysms uses a period of induced hypotension before aortography and consideration for surgical correction. There are 13 survivors of a series of 24 patients treated in this way.


Effects of the yeast RNA-binding protein Whi3 on the half-life and abundance of CLN3 mRNA and other targets.
Whi3 is an RNA binding protein known to bind the mRNA of the yeast G1 cyclin gene CLN3. It inhibits CLN3 function, but the mechanism of this inhibition is unclear; in previous studies, Whi3 made no observable difference to CLN3 mRNA levels, translation, or protein abundance. Here, we re-approach this issue using microarrays, RNA-Seq, ribosome profiling, and other methods. By multiple methods, we find that the whi3 mutation causes a small but consistent increase in the abundance of hundreds of mRNAs, including the CLN3 mRNA. The effect on various mRNAs is roughly in proportion to the density of GCAU or UGCAU motifs carried by these mRNAs, which may be a binding site for Whi3. mRNA instability of Whi3 targets may in part depend on a 3' AU rich element (ARE), AUUUUA. In addition, the whi3 mutation causes a small increase in the translational efficiency of CLN3 mRNA. The increase in CLN3 mRNA half-life and abundance together with the increase in translational efficiency is fully sufficient to explain the small-cell phenotype of whi3 mutants. Under stress conditions, Whi3 becomes a component of P-bodies or stress granules, but Whi3 also acts under non-stress condition, when no P-bodies are visible. We suggest that Whi3 may be a very broadly-acting, but mild, modulator of mRNA stability. In CLN3, Whi3 may bind to the 3' GCAU motifs to attract the Ccr4-Not complex to promote RNA deadenylation and turnover, and Whi3 may bind to the 5' GCAU motifs to inhibit translation.


Distribution of Xanthomonas oryzae pv. oryzae DNA modification systems in Asia.
The presence or absence of two DNA modification systems, XorI and XorII, in 195 strains of Xanthomonas oryzae pv. oryzae collected from different major rice-growing countries of Asia was assessed. All four possible phenotypes (XorI+ XorII+, XorI+ XorII-, XorI- XorII+ and XorI- XorII-) were detected in the population at a ratio of approximately 1:2:2:2. The XorI+ XorII+ and XorI- XorII+ phenotypes were observed predominantly in strains from southeast Asia (Philippines, Malaysia, and Indonesia), whereas strains with the phenotypes XorI- XorII- and XorI+ XorII- were distributed in south Asia (India and Nepal) and northeast Asia (China, Korea, and Japan), respectively. Based on the prevalence and geographic distribution of the XorI and XorII systems, we suggest that the XorI modification system originated in northeast Asia and was later introduced to southeast Asia, while the XorII system originated in southeast Asia and moved to northeast Asia and south Asia. Genomic DNA from all tested strains of X. oryzae pv. oryzae that were resistant to digestion by endonuclease XorII or its isoschizomer PvuI also hybridized with a 7.0-kb clone that contained the XorII modification system, whereas strains that were digested by XorII or PvuI lacked DNA that hybridized with the clone. Size polymorphisms were observed in fragments that hybridized with the 7.0-kb clone. However, a single hybridization pattern generally was found in XorII+ strains within a country, indicating clonal maintenance of the XorII methyl-transferase gene locus. The locus was monomorphic for X. oryzae pv. oryzae strains from the Philippines and all strains from Indonesia and Korea.


The research on the influences of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis.
To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49). We administered systemic vein chemotherapy for patients in the control group, and hyperthermal perfusion chemotherapy for the patients in the observation group in order to compare the subgroup levels of T lymphocytes, NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients in both groups. We also assayed the circulating tumor cells (CTC) in the peripheral blood of patients in both groups using the cell search method, and compared the efficacy using response evaluation criteria in solid tumors and the survival rates of patients in both groups using the Kaplan-Meier method. After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the patients in the observation group were significantly higher than those of the control group, but the levels of CD8+ of patients in the observation group was lower than that in the control group (p< 0.05). The levels of immunoglobulins (IgG, IgA, and IgM) in the observation group were higher than the control group (p < 0.05). The levels of NK cell cells were significantly lower than the control group (p < 0.05). The objective response rate, as well as the disease control rate of the observation group, were remarkably higher than those of the control group (p < 0.05). Compared to the control group, the observation group enjoyed a prolonged survival time, higher survival rate and significantly lower positive rate of CTC (p < 0.05). Better efficacy and tolerance, fewer toxic and side effects, improvement in the immunologic functions of patients for the indirect anti-tumor effect, a significant decrease in CTC of patients, and a higher long-term survival rate have been achieved in the treatment with hyperthermal perfusion chemotherapy combined with immunologic therapy for the advanced colorectal cancer patients with liver metastasis. Thus, it can serve as the preferable drug for the treatment of advanced colorectal cancer with liver metastasis.


Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine.
Parthenocarpic fruit development (PFD) reduces fruit yield and quality in grapevine. Parthenocarpic seedless berries arise from fruit set without effective fertilization due to defective pollen germination. PFD has been associated to micronutrient deficiency but the relation of this phenomenon with pollen polymorphism has not been reported before. In this work, six grapevine cultivars with different tendency for PFD and grown under micronutrient-sufficient conditions were analyzed to determine pollen structure and germination capability as well as PFD rates. Wide variation in non-germinative abnormal pollen was detected either among cultivars as well as for the same cultivar in different growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896), suggesting that natural parthenocarpy is related to defective pollen development. Such relation was not observed when PFD was analyzed in grapevine plants exposed to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre-anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates without significative changes in abnormal pollen was determined. Although these plants were maintained at sufficient boron (B) condition, a down-regulation of the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content in GA-treated plants was established. These results suggest that impairment in B mobility to reproductive tissues and restriction of pollen tube growth could be involved in the GA-induced parthenocarpy.


[Physiological, pathophysiological and clinical significance of chromogranins/secretogranins].
This paper investigates the fundamental knowledge, build-up, as well as essential structural and important features of the big family of chromogranins/secretogranins. Previously the different properties and the slightly diverging funcional relations of the two family members were in focus. Later on, it has been discovered that they are essentially two similar compounds with identical structures and functions, and they are chemically, biochemically related. From details discovered so far we can tell that they are long polypeptid chains formed from amino acids. Based on insights gained until now we can also state that these compounds are formed in Ca++ containing environments with acidic pH. Among the compounds there are several molecules which have characteristic oligosacharid groups. This is especially interesting because oligosacharid chains with sialic acid in terminal position play an important role in the recognising and connectional processes. The chromogranins/secretogranins are mostly formed in neuroendocrine cells, but are also capable of building up in any cell type in the organism during pathological processes. Intracellular biogenesis takes place in the dense endoplasmatic reticulum across the mitochondrium, developing biogenetic granulums, followed by the stimulus-motivated secretum (exocytosis). The next stage of the molecular development is the specific break-up of the long polypeptid chains into shorter fragments. These fragments have individual effects. Some important clinical (diagnostic, prognostic) significance and connections are also touched upon in this paper, however, the cardiovascular, immunological systems and the tumors are mostly in focus. There are more immunological, cardiovascular and tumoral data. It is stated that as these molecules are in close connection with all of the organisms and systems of the body, a new chief organisator system has been identified. This chief organisator is closely connected with the central nervous system. Orv Hetil. 2017; 158(28): 1092-1099.


Colon Cancer Screening - Is It Time Yet?
The month of March is dedicated to Colon Cancer Awareness. Worldwide, colorectal cancer (CRC) incidence has been on the rise. It is currently the third most common cancer in men (746,000 cases, 10.0% of the total) and the second in women (614,000 cases, 9.2% of the total).1 Arecent meta-analysis reported a 61% risk reduction in CRC incidence with colonoscopy.2 Unlike screening programs for breast and prostate cancers, not only has CRC screening reduced mortality from colon cancer and detected early CRC, it has also decreased the incidence of CRC through detection and removal of pre-cancerous lesions. Studies have shown that screening for colorectal cancer provided 152 to 313 life-years-gained (LYG) per 1000 forty-year-old individuals.3 Anumber of modalities exist for CRC screening, which can broadly be categorized into stool-based tests and direct visualization tests. Stool-based tests include fecal occult blood testing (FOBT), fecal immunochemical testing (FIT) and stool DNAtesting. Direct visualization tests include endoscopic procedures such as colonoscopy and flexible sigmoidoscopy; and radiographic tests such as CT colonography, which has largely replaced air contrast barium enemas.4 The only reported population-based data for CRC in Pakistan comes from Bhurgri et al. in 2011.5It described Pakistan as a low risk region with an age standardized incidence rate (ASR) world per 100,000 of 7.1 in males and 5.2 in females, but with a much younger age and advanced stage at diagnosis. The ratio for individuals diagnosed with CRC under the age of 40, as oppose to over 40 years, was 3:1, which is much higher than the international average. Noteworthy as well, is an increase in incidence especially among men, noted between the study periods of 1995-1997 and 1997-2002. It ranks 7th in incidence among males, and 8th among females, with tobacco related malignancies topping the list.6 There has since been additional cross-sectional data from Pakistan echoing these findings of a younger age and advanced disease at presentation.7 Speaking from a public health perspective, Pakistan, while still battling communicable diseases, is now seeing an increasing incidence of non-communicable diseases population-based screening programs for CRC were not justified in most developing countries, citing low reported incidence and low resource health authorities; but that in limited regions with an ageing population and a shift to Western lifestyle, organized screening strategies needed to be developed. This can well be extrapolated to large urban centers in Pakistan. In a resource poor, conservative country like Pakistan, with poor health literacy, there exist many barriers to CRC screening which were summed up very articulately by Ahmed F in 2013. Quite appropriately, areas identified for further pursuit included, among others, the training of gastroenterologists, especially female ones, less expensive and more culturally acceptable screening options, and cost-effectiveness analyses. The recipe for any cancer screening program to be successful, begins with epidemiological data to document disease burden. There has not been any population-based cancer registry to report incidence data for the past few years. There is also no centralized cancer registry to effectively unify and coordinate data from across the country. Furthermore, even with a cancer registry there is no mandated reporting of malignancies from a health policy standpoint, as exists in the more developed world. The last population-based data we have for CRC was for cases reported until 2002, and there was already an increase in incidence noted in less than a decade, starting in 1995.5 Health awareness is another important factor. There is no data from Pakistan regarding patient or physician awareness regarding colon cancer. If one is to extrapolate, a cross-sectional study on breast cancer awareness, for which Pakistan demonstrates one of the highest incidences worldwide,6 reported that a mammogram had been performed in only 4.9 % of women in the cohort, while 61.5 % of the remainder had never even heard about it.7 It is also unclear if we have the infrastructure including endoscopy centers and adequate numbers of gastroenterologists to service the population at large. FOBTis available and cheap, but there is no data regarding the availability of FITor stool DNAtesting. In the absence of health insurance, it will certainly be a challenge to make CRC screening widely accessible. At what point does a disease warrant attention? While we may not have the luxury or the immediate necessity to introduce mass population-based CRC screening, we can certainly start with individual screening in populations who are at high risk of colorectal cancer due to family history and have adequate access to healthcare. There should be a concerted drive to revitalize cancer registration in order to guide health policy and to have an effective national cancer control program. Awareness programs are also needed to be established for the public and, specifically, for physicians as well.


Efficacy of A Poly(MeOEGMA) Brush on the Prevention of Escherichia coli Biofilm Formation and Susceptibility.
Urinary tract infections are one of the most common hospital-acquired infections, and they are often associated with biofilm formation in indwelling medical devices such as catheters and stents. This study aims to investigate the antibiofilm performance of a polymer brush-poly[oligo(ethylene glycol) methyl ether methacrylate], poly(MeOEGMA)-and evaluate its effect on the antimicrobial susceptibility of Escherichia coli biofilms formed on that surface. Biofilms were formed in a parallel plate flow chamber (PPFC) for 24 h under the hydrodynamic conditions prevailing in urinary catheters and stents and challenged with ampicillin. Results obtained with the brush were compared to those obtained with two control surfaces, polydimethylsiloxane (PDMS) and glass. The polymer brush reduced by 57% the surface area covered by E. coli after 24 h, as well as the number of total adhered cells. The antibiotic treatment potentiated cell death and removal, and the total cell number was reduced by 88%. Biofilms adapted their architecture, and cell morphology changed to a more elongated form during that period. This work suggests that the poly(MeOEGMA) brush has potential to prevent bacterial adhesion in urinary tract devices like ureteral stents and catheters, as well as in eradicating biofilms developed in these biomedical devices.


Predictive value of electrocardiographic T-wave morphology parameters and T-wave peak to T-wave end interval for sudden cardiac death in the general population.
Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample. A total of 4 T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46% men; mean age 50.9±12.5 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up time of 7.7±1.4 years, 72 SCDs had occurred. In univariable analyses, all T-wave morphology parameters were associated with an increased SCD risk. In multivariable Cox models, T-wave morphology dispersion and total cosine R-to-T remained as predictors of SCD, with T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4 [95% confidence interval 1.1-1.7, P=0.001] per 1 SD increase in the loge T-wave morphology dispersion). In contrast, TPE was not associated with SCD in univariable or multivariable analyses. Electrocardiographic T-wave morphology parameters describing the 3-dimensional shape of the T-wave stratify SCD risk in the general population, but we did not find an association between TPE and SCD.


Morphological changes in adrenal cortex--the final effect of angiotensin II receptor antagonists.
The influence of losartan, angiotensin receptor on the histological image of the adrenal glomerular layer of white rats was revealed. The drug was administered in the therapeutic and ten times higher dose. It was manifested by the decrease of glandular cells and prevalence of blastic cells of the cortex. After a 2-month break in drug administration, the reconstruction of glandular cells was noticed, which could indicate that the observed changes are of transitory character.


Colorectal mucin histochemistry in health and disease: a critical review.
Neoplastic, inflammatory and regenerative processes affecting colorectal mucosa are associated with alterations in structure of epithelial mucin. This review collates mucin-, lectin-, and immuno-histochemical observations on colorectal mucins and introduces recent molecular genetic insights into the structure of the protein backbone of mucins. The numerous structural modifications uncovered by the various technical approaches have been reduced to a few manageable principles that are of relevance to both researcher and diagnostic pathologist. Particular attention is drawn to the need to appreciate the limited specificities of probes, the confounding influences of anatomical site and genetic factors (necessitating the use of appropriate positive and negative control tissues) and the precise location of secretory material. In the past, insufficient attention has been given to the effects of altered differentiation including metaplasia and differing lineage expression in epithelial disorders of growth. It is likely that certain changes loosely ascribed to goblet cell mucin, such as neo-expression of blood group antigens and anomalous expression of core carbohydrate structures, do not occur at all. Critical examination of available data point to only two consistent and unequivocal changes affecting goblet cell mucin in pathological processes: loss of O-acetyl substituents at sialic acid C4 and C7,8,9 and increased sialylation. Furthermore, there are no neoplasia-specific alterations in mucins documented to date. All neoplasia-associated changes have been described in non-neoplastic lesions also.


Genetic differences between wild and hatchery-bred brown trout (Salmo trutta L.) in single nucleotide polymorphisms linked to selective traits.
To study effects from natural selection acting on brown trout in a natural stream habitat compared with a hatchery environment, 3,781 single nucleotide polymorphism (SNP) markers were analyzed in three closely related groups of brown trout (Salmo trutta L.). Autumn (W/0+, n = 48) and consecutive spring (W/1+, n = 47) samples of brown trout individuals belonging to the same cohort and stream were retrieved using electrofishing. A third group (H/1+, n = 48) comprised hatchery-reared individuals, bred from a mixture of wild parents of the strain of the two former groups and from a neighboring stream. Pairwise analysis of FST outliers and analysis under a hierarchical model by means of ARLEQUIN software detected 421 (10.8%) candidates of selection, before multitest correction. BAYESCAN software detected 10 candidate loci, all of which were included among the ARLEQUIN candidate loci. Body length was significantly different across genotypes at 10 candidate loci in the W/0+, at 34 candidate loci in the W/1+ and at 21 candidate loci in the H/1+ group. The W/1+ sample was tested for genotype-specific body length at all loci, and significant differences were found in 10.6% of all loci, and of these, 14.2% had higher frequency of the largest genotype in the W/1+ sample than in W/0+. The corresponding proportion among the candidate loci of W/1+ was 22.7% with genotype-specific body length, and 88.2% of these had increased frequency of the largest genotype from W/0+ to W/1+, indicating a linkage between these loci and traits affecting growth and survival under this stream's environmental conditions. Bayesian structuring of all loci, and of the noncandidate loci suggested two (K = 2), alternatively four clusters (K = 4). This differed from the candidate SNPs, which suggested only two clusters. In both cases, the hatchery fish dominated one cluster, and body length of W/1+ fish was positively correlated with membership of one cluster both from the K = 2 and the K = 4 structure. Our analysis demonstrates profound genetic differentiation that can be linked to differential selection on a fitness-related trait (individual growth) in brown trout living under natural vs. hatchery conditions. Candidate SNP loci linked to genes affecting individual growth were identified and provide important inputs into future mapping of the genetic basis of brown trout body size selection.


BNIP3L Is a New Autophagy Related Prognostic Biomarker for Melanoma Patients Treated With AGI-101H.
Skin melanoma belongs to the most invasive malignancies with no cure for a progressing disease. Personalized therapy would allow for the selection of patients that will benefit from treatment. For this purpose, proper predictive biomarkers must be defined. Allogeneic whole-cell gene-modified therapeutic melanoma vaccine (AGI-101H) was applied in advanced melanoma patients. Humoral responses were analyzed using SEREX, and in silico gene expression analysis in TCGA melanoma patients was performed. A specific antibody response was raised against an antigen identified as BNIP3L, which correlated with a good prognosis. Moreover, AGI-101H directs an immune response against autophagy, as BNIP3L is a marker of this process. Medium and high expression of BNIP3L was also linked with longer overall survival. BNIP3L is a candidate prognostic marker of clinical outcome of melanoma patients treated with AGI-101H, and may be considered as a prediction marker for patient survival.


5-Azacytidine-resistant mutants of Chlorella virus IL-3A.
Many dsDNA-containing viruses which infect the unicellular, eukaryotic Chlorella-like green alga strain NC64A encode for DNA methyltransferases and DNA site-specific (restriction) endonucleases. We have hypothesized that these endonucleases help degrade host DNA permitting deoxynucleotides to recycle into virus DNA. This hypothesis was tested by isolating deletion mutants of Chlorella virus IL-3A lacking functional genes for the cytosine methyltransferase M.CviJI and the cognate site-specific endonuclease CviJI. The growth and burst sizes of the mutants and parent virus were identical. Also host nuclear and chloroplast DNAs disappeared from infected cells at the same rates. Thus M.CviJI and CviJI activities are not required for IL-3A replication and CviJI activity is not essential for host DNA degradation.


Association Between Polymorphisms in Cytokine Gene and Viral Infections in Renal and Liver Transplant Recipients: A Systematic Review.
Although transplantations are associated with an increased risk of post-transplantation infections, they greatly improve life expectancy and patients' quality of life. Cytokine genes play an important role in the success of transplants due to their immunological functions. A systematic review was conducted to evaluate cytokine gene polymorphisms and risk of cytomegalovirus (CMV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in kidney and liver transplant recipients. A systematic search was conducted using PubMed, EMBASE, Medline and Google Scholar from their inception until January 28, 2019 using appropriate key words. Review articles, case reports or series, studies conducted on non-human subjects and published in languages other than English were excluded. Data were abstracted using a standardized form. The quality of the studies included was assessed using "Risk of Bias Assessment tool for Non-randomized Studies (RoBANS)". Thirty-one studies met our inclusion criteria; populations studied were diverse with a sample ranging from 20 to 1,671. Nineteen studies evaluated Interleukin (IL)-28B polymorphism, while six studies evaluated interferon lambda (IFN-λ) gene polymorphisms and their impact on CMV, HCV, and HBV progression. Polymorphisms in IL-10 gene were investigated in six studies. Polymorphisms in IL-12B and IL-1B gene were associated with a higher risk of developing CMV infections while polymorphisms in IL-28B were associated with a lower incidence of CMV infection in renal transplant recipients. Similarly, polymorphisms in IL-28B were associated with higher liver dysfunction from HBV infection in liver transplant recipients. Studies included had low risk of bias. Cytokine gene polymorphisms IL-12B and IL-1B were found to be associated with an increased risk of infection in kidney transplants and IL-28B in liver transplant recipients. However, the small number and heterogeneity of studies limits the generalization of our results. Further research may lead to finding these associations in larger studies which perhaps improve the use of genetic testing and targeted antiviral therapy. This will further reduce the risk of viral infections associated with cytokine gene polymorphisms in post renal and liver transplant recipients.