Knowledge, attitudes and practices of animal farm owners/workers on antibiotic use and resistance in Amhara region, north western Ethiopia.
Inappropriate use of antibiotics in animal and human plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. Although extensive use of these antibiotics could contribute to the development of drug resistance, information on the knowledge, attitude and practice of antimicrobial resistance and use among animal farm owners/workers in north western Ethiopia is rare. The objective of the present study was to assess knowledge, attitude and practice of animal farm owner/workers towards antibiotic resistance and use in Amhara regional state north western Ethiopia. A cross sectional study was conducted in selected cities of Amhara regional state from January to February, 2020. Data was collected from 91 participants using structured questionnaire and analyzed using SPSSS version 23. The results showed that 96.7% of respondents gave antibiotics to treat their livestock from different sources. Most of the respondents bought their antibiotics from private pharmacies without prescription and the most frequently mentioned antibiotics used to treat animal diseases was tetracycline (76.9%), followed by ampicillin (72.5%). Although, 90.1% of the animal farm owners heard about antibiotics and antibiotic resistance from different sources, they did not know the factors contributing to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animals' health. Using the mean score 4.44 ± 0.15 as the cut-off, half of the animal farm owners/workers had good knowledge about antimicrobial resistance and use. 52.5% of animal farm owners/workers had positive attitudes towards wise antibiotic use and resistance with a mean score of 28.4 ± 0.5. However, 52.75% participants had poor practice with the mean score of practice 4.95 ± 0.17. Better knowledge, positive attitudes and better practices on antibiotic use and resistance were associated with farm owners/workers who engaged in higher education. Although poor awareness on antimicrobial resistance was perceived by 76.9% of respondents as very important factors that contribute to increasing antibiotic resistance, increasing the use of complementary treatments was perceived by the majority of respondents as very important strategies that contribute to reduce antibiotic use and resistance. The current study disclosed that there is low level of awareness among animal farm owners about the correct use of antibiotics and resistance. It is necessary to raise awareness, develop and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area.


A guide for mutagenicity testing using the dominant lethal assay.
The dominant lethal assay has been used and continues to be used to provide information about the effects of chemicals on the gonadal cells of male animals. Guidelines for conducting this test are useful but as with any guideline scientists should avoid interpreting them as protocols. Thus this document is a general approach to dominant lethal testing and should be used in conjunction with other available protocols and procedures.


Automatic tachycardia recognition.
A microcomputer algorithm for tachycardia identification, suitable for use in an implanted antitachycardia pacemaker, is described. The system employs an atrial and ventricular electrogram, detects a sustained fast rate in either chamber, and awakens the main program to perform detailed analysis of the tachycardia and its immediately preceding beats. The algorithm distinguishes atrial, ventricular, and AV nodal and re-entrant tachycardia from high rates due to sinus tachycardia. For testing of the program, we used a data base of twenty-two tape-recorded and documented arrhythmias provoked during electrophysiologic studies in which atrial and ventricular bipolar electrodes were in place; twenty-one were successfully detected. These included atrial fibrillation, atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, AV re-entrant tachycardia using an accessory pathway, and ventricular tachycardia with and without ventriculo-atrial conduction.


Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA-SCID patients.
Recently, we investigated a Belgian patient with severe combined immune deficiency caused by a dysfunction of the gene for adenosine deaminase (ADA-SCID), which was found to be due to a 3.2-kb deletion spanning the promoter and the first exon of the ADA gene (Berkvens et al., 1987, Eur. J. Pediatr. 146:329). No ADA-specific RNA could be detected in primary fibroblasts derived from this patient. In the present paper we establish via direct sequencing of in vitro amplified DNA that the 3250-bp deletion is due to a recombination within the left arms of two direct AluI repeats. This mutation is identical to one reported for an unrelated patient in the United States (Markert et al., 1988, J. Clin. Invest. 81:1323-1327).


Intraoperative Assessment of Coronal Balance with Long Cassette Radiographs in Adult Thoracolumbar Deformity Correction.
To describe the use of intraoperative anteroposterior long cassette radiographs (APLCRs) to guide kickstand rod application in adult spinal deformity. A retrospective chart review was performed to identify patients with adult thoracolumbar and coronal plane deformity undergoing open segmental decompression with spinopelvic fixation and deformity correction between October 2017 and June 2019 who had APLCRs after rod placement. In patients with persistent intraoperative coronal deviations, a kickstand rod was placed. This supplemental rod was anchored to an iliac screw and to the construct via a pair of side-to-side connectors. A distractor was expended between a vice grip plyer on the kickstand and side-to-side connector to apply a lateralizing force to reduce the degree of deviation. Of 15 patients who underwent T3-ilium fusion with spinal deformity correction with intraoperative APLCRs, 7 underwent kickstand placement. Mean preoperative coronal deviation was similar between cohorts (4.3 cm vs. 2.2 cm, P = 0.09), but was greater intraoperatively in the kickstand cohort (4.3 cm vs. 0.6 cm, P < 0.001). Postoperative coronal deviation was similar between groups (2.1 cm vs. 1.8 cm, P = 0.37). Preoperative fractional lumbar curve was significantly greater in patients requiring a kickstand (23° vs. 35°, P = 0.02), but the major thoracolumbar curve was similar between groups (43° vs. 35°, P = 0.14). Intraoperative APLCRs can help guide application of a kickstand rod in adult thoracolumbar deformity correction. Patients with a greater fractional lumbar curve may derive greater benefit of kickstand usage, independent of major curve magnitude.


[Influence of long term neuroleptic therapies on the function of the peripheral motoric neuron? (author's transl)].
In electroneurographic and electromyographic examinations of 37 patients who had taken neuroloptic drugs for many years a delay in the conduction velocity of the ulnar nerve was found in one case, of the fibular nerve in five cases. Spontaneous electrical activity was not observed in any case. Deviations from the mean of the action potential were found more frequently, however less markedly than in alcoholics. It is suggested that these small changes are caused by the slight anticholinergic action of major tranquilizers.


Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk.
We evaluated the association of a polymorphism in TCF7L2 (RS12255372) in the WNT signaling pathway, which previously has been strongly associated with risk of Type II Diabetes, with colorectal cancer (CRC) and adenoma in the prospective Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. Hyperinsulinemia may be related to the risk of colon adenoma and cancer, therefore this variant associated with reduced insulin secretion would be predicted to be inversely associated with colorectal cancer. Overall, in the NHS and HPFS, there was suggestive evidence for an inverse association associated with homozygosity for the minor allele of RS12255372 (TCF7L2 TT) and CRC (conditional and covariate adjusted OR = 0.63, 95% CI: 0.37-1.08; P for heterogeneity 0.52 for the association in women and men). In summary, the marginal association of the TCF7L2 SNP with CRC might be due to chance, but warrants further laboratory and epidemiological investigation.


Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KATP channels through CaMKII activation.
Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation plays a critical role in cardiomyocyte (CM) apoptosis and arrhythmia. Functional ATP-sensitive potassium (KATP) channels are essential for cardiac protection during ischemia. In cultured CMs, L5 low-density lipoprotein (LDL) induces apoptosis and QTc prolongation. L5 is a highly electronegative and atherogenic aberrant form of LDL, and its levels are significantly higher in patients with cardiovascular-related diseases. Here, the role of L5 in cardiac injury was studied by evaluating the effects of L5 on CaMKII activity and KATP channel physiology in CMs. Cultured neonatal rat CMs (NRCMs) were treated with a moderate concentration (ie, 7.5 μg/mL) of L5 or L1 (the least electronegative LDL subfraction). NRCMs were examined for apoptosis and viability, CaMKII activity, and the expression of phosphorylated CaMKIIδ and NOX2/gp91phox. The function of KATP and action potentials (APs) was analyzed by using the patch-clamp technique. In NRCMs, L5 but not L1 significantly induced cell apoptosis and reduced cell viability. Furthermore, L5 decreased Kir6.2 expression by more than 50%. Patch-clamp analysis showed that L5 reduced the KATP current (IKATP) density induced by pinacidil, a KATP opener. The partial recovery of the inward potassium current during pinacidil washout was susceptible to subsequent inhibition by the IKATP blocker glibenclamide. Suppression of IKATP by L5 significantly prolonged the AP duration. L5 also significantly increased the activity of CaMKII, the phosphorylation of CaMKIIδ, and the expression of NOX2/gp91phox. L5-induced apoptosis was prevented by the addition of the CaMKII inhibitor KN93 and the reactive oxygen species scavenger Mn (III)TBAP. L5 but not L1 induces CM damage through the activation of the CaMKII pathway and increases arrhythmogenicity in CMs by modulating the AP duration. These results help to explain the harmful effects of L5 in cardiovascular-related disease.


Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders.
We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.


Increased Seat Dump Angle in a Manual Wheelchair Is Associated With Changes in Thoracolumbar Lordosis and Scapular Kinematics During Propulsion.
To quantify and compare spinal curvature and shoulder kinematics throughout the manual wheelchair (MWC) propulsion cycle for individuals with spinal cord injury (SCI) who were seated at 2 different seat dump angles. Single-group, repeated-measures study. Academic medical center. Individuals (N=28) with SCI or spinal cord disease who used MWCs completed a telephone screening, and 21 of them were eligible and completed the study. Participants' personal MWCs were modified to have seat dump angles of 0° or 14°, with a vertical backrest. Participants completed at least 3 propulsion cycles in each condition, during which spine and shoulder motion data were collected with fiberoptic and electromagnetic sensors, respectively. Thoracolumbar spinal curvature, glenohumeral kinematics, and scapulothoracic kinematics at the start of push (SP), mid-push (MP), end of push (EP), and mid-recovery. Participants had significantly less lordosis in the 14° condition for all propulsion events. Median differences ranged from 2.0° to 4.6°. Lordosis differences were more pronounced in those with low SCI. Scapulothoracic internal rotation was increased in the 14° condition at SP and MP (mean differences, 2.5° and 2.7°, respectively). Relative downward rotation increased in the 14° condition at SP and MP (mean differences, 2.4° and 2.1°, respectively). Scapulothoracic differences were more pronounced in those with high SCI. No glenohumeral rotations were significantly different between the conditions. Scapulothoracic kinematics and spinal curvature differences during propulsion may be associated with the position of other body segments or postural stability. Because no differences were observed at the glenohumeral joint, the risk of subacromial impingement may not be affected by this seat angle change.


Surgery in hydrocephalus of tubercular origin: challenges and management.
Hydrocephalus of tubercular origin is one of the most dreaded and difficult to manage complications of brain tuberculosis. Traditionally, the management has been ventriculoperitoneal shunting, but in recent years emerging interest is in endoscopic ventriculostomy. In this article, we discuss the management protocol of hydrocephalus in various stages of disease. A total of 424 cases of tubercular origin hydrocephalus were managed between years 2000 and 2009. Initially the cases were managed by ventriculoperitoneal shunting, which was followed by use of endoscopic third ventriculostomy. Drug-resistant cases were also encountered and managed according to drug sensitivity. The results provided through evaluation of retrospective data showed a high mortality in cases of hydrocephalus of acute origin if endoscopic third ventriculostomy was performed. The cerebrospinal fluid protein level and neurological status of the patient determined the success or failure of the procedure. For better management, patients were divided into six groups and their management underlined. The cases of tubercular meningitis with aqueductal stenosis presenting in early stages should be given a trial of endoscopic third ventriculostomy where chronic burnt-out cases or cases with communicating hydrocephalus should be managed by ventriculoperitoneal shunting.


Retrospective evaluation of therapeutic plasma exchange treatment in a pediatric intensive care unit: Single-center experience.
The aim of this study is to characterize the clinical indications, outcomes, and complications of therapeutic plasma exchange (TPE) in pediatric intensive care unit. A retrospective study was conducted on critically ill patients who received TPE. A dataset of 672 treatments administered to 102 patients was analyzed. The most common indication for TPE was COVID-19-related clinical conditions, followed by sepsis (24.5%), neurological diseases (9.8%) and renal diseases (6.9%). None of our patients died due to TPE-related complications, and the most common complication during and after the TPE was hypotension (21.7%). Although TPE is riskier to provide to critically ill children, our experience indicates that it can be performed relatively safely in critically ill children with appropriate treatment indications. In particular, indications, onset time, number of sessions and other procedures should be standardized for the pediatric age group.


Use of mycophenolate mofetil in liver transplantation: a literature review.
Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.


Direct Detection of Influenza A and B Viruses in Less Than 20 Minutes Using a Commercially Available Rapid PCR Assay.
We compared an FDA-cleared rapid (<20 min) PCR assay (Cobas Liat; Roche Diagnostics) to our routine influenza A and B real-time PCR assay (Simplexa Flu A/B & RSV Direct; Focus Diagnostics) using respiratory swabs (n = 197). The Cobas Liat influenza A and B assays demonstrated sensitivities of 99.2% (123/124) and 100% (23/23), respectively, while showing a specificity of 100% for each target.


Mesh cancer: long-term mesh infection leading to squamous-cell carcinoma of the abdominal wall.
It is recognized that chronic inflammation can cause cancer. Even though most of the available synthetic meshes are considered non-carcinogenic, the inflammatory response to an infected mesh plays a constant aggression to the skin. Chronic mesh infection is frequently the result of misuse of mesh, and due to the challenging nature of this condition, patients usually suffer for years until the infected mesh is removed by surgical excision. We report two cases of squamous-cell carcinoma (SCC) of the abdominal wall, arising in patients with long-term mesh infection. In both patients, the degeneration of mesh infection into SCC was presumably caused by the long-term inflammation secondary to infection. Patients presented with advanced SCC behaving just like the Marjolin's ulcers of burns. Radical surgical excision was the treatment of choice. The involvement of the bowel played an additional challenge in case 1, but it was possible to resect the tumor and the involved bowel and reconstruct the abdominal wall using polypropylene mesh as onlay reinforcement, in a single stage operation. He is now under adjuvant chemotherapy. The big gap in the midline after tumor resection in case 2 required mesh bridging to close the defect. The poor prognosis of case 2 who died months after the operation, and the involvement of the armpit, groin and mesenteric nodes in case 1 shows how aggressive this disease can be. Infected mesh must be treated early, by complete excision of the mesh. Long-standing mesh infection can degenerate into aggressive squamous-cell carcinoma of the skin.


Successful treatment of recurrent carotid in-stent restenosis and drug-eluting balloon failure with a coronary bioresorbable vascular scaffold: A case report.
Carotid in-stent restenosis is associated with substantial risk of recurrent restenosis, even after drug-eluting balloon usage. We hereby report the case of a patient with recurrent carotid in-stent restenosis and drug-eluting balloon failure treated with a coronary bioresorbable vascular scaffold, achieving a satisfactory acute and long-term result, as disclosed by duplex ultrasound scan performed more than 1 year after the procedure. While awaiting for external validation, this clinical vignette supports expanding the armamentarium of endovascular specialists focusing on carotid artery disease, while providing further proof of the safety and efficacy of current bioresorbable vascular scaffolds.


Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review.
To evaluate the safety, efficacy, and effectiveness of TNF antagonists in patients with sarcoidosis. A descriptive study of a case series registered in BIOBADASER and a systematic review was performed. The search strategy of articles published between 1998 and July 2011 in Medline, Embase, and the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF antagonists. Seven patients treated with infliximab (IFX) and 1 with etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER 2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response in 2 cases. Eight serious adverse events were reported. In the selected 69 of 2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials, favorable response of the lung disease was reported with IFX. In other randomized clinical trials, no improvement of ocular manifestations was reported with ETN. In the cases series, results were diverse. Mean weighted rates of adverse events, infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per 100 patient-years, respectively. There is insufficient evidence to ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be effective in selected manifestations of the disease. Before starting treatment of sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be considered on an individual basis.


Reintegrating young combatants: do child-centred approaches leave children—and adults—behind?
This article uses recent experience in Angola to demonstrate that young fighters were not adequately or effectively assisted after war ended in 2002. The government's framework excluded children from accessing formal disarmament, demobilisation and reintegration (DDR) programmes, and its subsequent attempts to target children have largely failed. More critically the case of Angola calls into question the broader effectiveness and appropriateness of child-centred DDR. First, such targeting is inappropriate to distinct post-conflict contexts and constructs a 'template child' asserted to be more vulnerable and deserving than adult ex-combatants, which does little to further the reintegration of either group, or the rights of the child in a conflict context. Second, child-centred reintegration efforts tend to deny children agency as actors in their own reintegration. Third, such efforts contribute to the normalisation of a much larger ideational and structural flaw of post-conflict peace building, wherein 'success' is construed as the reintegration of large numbers of beneficiaries back into the poverty and marginalisation that contributed to conflict in the first place.


A Comparison of Estimated Cost Savings from Potential Reductions in Hospital-Acquired Conditions to Levied Penalties Under the CMS Hospital-Acquired Condition Reduction Program.
The Hospital-Acquired Condition Reduction Program (HACRP) from the Centers for Medicare & Medicaid Services (CMS) reduces Medicare payments to hospitals with high rates of hospital-acquired conditions (HACs) by 1% each year. It is not known how the savings accruing to CMS from such penalties compare to savings resulting from a reduction in HACs driven by this program. This study compares the reported savings to CMS from financial penalties levied under the HACRP with savings resulting from potential reductions in HACs. Using a random sample of 20% of Medicare claims data (January 1, 2009-September 30, 2014), the research team evaluated the association between HACs and 90-day episode spending (adjusted to 2015 dollars), then estimated potential annual savings to CMS if there was a relative decrease in incidence of all HACs by 1%-20%. These savings were then compared to the actual collected HACRP penalties reported by CMS in 2015. All HACs were associated with significant increases in total 90-day episode spending, ranging from $3,183 for iatrogenic pneumothorax to $21,654 for postoperative hip fracture. The total estimated savings to Medicare from potential reduction in all HACs ranged from $2.2 million to $44 million per year, an amount much lower than the $361 million in penalties levied on hospitals per year for HACs. The penalties levied under the HACRP far exceed the potential cost savings accruing from a 1%-20% reduction in HACs that might result from hospitals' efforts in response to the program.


Protective effects of quercetin and its metabolites on H2O2-induced chromosomal damage to WIL2-NS cells.
We investigated chromosomal damage caused by a typical flavonoid, quercetin, and its two conjugates, quercetin-3-O-sulfate and isorhamnetin, and their protective effects against chromosomal damage induced by H2O2. The chromosomal damage was detected by the cytokinesis-block micronucleus (CBMN) assay using a lymphoblastoid cell line, WIL2-NS. We found that quercetin itself induced chromosomal damage at 10 microM, but quercetin-3-O-sulfate and isorhamnetin did not induce damage up to 30 microM. In the medium used for the CBMN assay, quercetin (at 100 microM) generated a high concentration of H2O2, but the two conjugates did not at the same concentration. On the other hand, pretreatment with quercetin (at 1 microM), quercetin-3-O-sulfate (at 10 microM), and isorhamnetin (at 5 microM) prevented H2O2-induced chromosomal damage to WIL2-NS cells. These findings suggest that the induction and prevention of H2O2-induced chromosomal damage are different between quercetin and its metabolites.


Combining radiation therapy and cancer immune therapies: From preclinical findings to clinical applications.
Besides its direct cytotoxic effect on the tumor cells, radiation therapy is also able to elicit an immune-mediated systemic anti-tumor response, resulting in tumor regression in irradiated sites but also within distant out of field secondary lesions and providing a long-term anti-tumor response. It is now clear that associating ionizing radiation with immune therapies can enhance radio-induced anti-tumor immune responses. Over the last decade, such a combination aroused considerable interest among the scientific community, with many preclinical models and clinical trials, using many types of immune therapies and radiation regimens. In this article, we summarize the main mechanisms underlying radio-induced anti-tumor responses. We will then present an extended overview of the recent preclinical and clinical research built on this background of combined radiation and immune therapy, shedding light on what we know so far about such a promising strategy.


Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1.
To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. The rats were randomly divided into 4 groups (n=12 in each group): the normal control, isoproterenol (ISO), ISO combined with low-dose curcumin (ISO+Cur-L), and ISO combined with high-dose curcumin (ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin (150 or 300 mg•kg-1•day-1) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type I/III, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test the proliferation of fibroblast. Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type I/III in hearts (P<0.05). In addition, curcumin directly inhibited angiotensin (Ang) II-induced fibroblast proliferation and collagen type I/III expression in cardiac fibroblasts (P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation, decreased TGF-β1, MMP-9 and TIMP-1 expression (P<0.05) but had no effects on Smad3 in Ang II incubated cardiac fibroblasts. Curcumin reduces cardiac fibrosis in rats and Ang II-induced fibroblast proliferation by inhibiting myofibroblast differentiation, decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1, MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.


Enhancement of voluntary alcohol consumption in rats by clofibrate feeding.
Clofibrate is known to be an inducer of alcohol- and acetaldehyde dehydrogenase. Therefore, male rats were offered increasing amounts of alcohol over a period of three months. Eventually they could choose between a 30% alcohol solution and tap water which was available ad lib. Animals were sacrificed after further 1 1/2 months of clofibrate feeding. Before clofibrate feeding voluntary intake of alcohol was 3.47 g/kg per day and increased up to 7.77 g/kg per day, i.e., by 123% within the clofibrate feeding period while the alcohol intake of controls increased from 3.84 to 4.88 g/kg per day, i.e., by only 27%. Food consumption increased in the clofibrate control group, whereas in the alcohol drinking clofibrate group the total caloric intake increase was due mainly to the enhancement of alcohol consumption. Relative liver weight was increased by clofibrate in the non-drinking as well as in the drinking group by 59%. Measurements of triglycerides and cholesterol exhibited changes typical for clofibrate in ethanol drinking and non-drinking animals. Probably the clofibrate-alcohol interaction results in accelerated ethanol metabolism and increased metabolic tolerance by induction of the ethanol detoxifying system in the liver.


Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth.
To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation). Case-control association study. A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks). Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing. Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045). Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.


Finding the fittest fold: using the evolutionary record to design new proteins.
For many years, the holy grail of protein engineering has been the design of artificial amino acid sequences that fold into stable proteins with desired functions. In the current issue of Nature, two papers from the Ranganathan group (Russ et al., 2005; Socolich et al., 2005) report remarkable success in the design of artificial WW domains. Their method, termed statistical coupling analysis (Lockless and Ranganathan, 1999), does not use structural or physicochemical information but instead extracts information about essential patterns of amino acids from the evolutionary record.


Crucial importance of using a sliding calliper to measure distance for carotid-femoral pulse wave velocity assessment.
In the past, different methods have been used to measure the carotid-femoral distance for the assessment of pulse wave velocity (PWV). However, the latest consensus published advises to use 80% of the direct straight carotid-femoral distance (D(0.8)) using either a flexible tape or a sliding calliper. We studied the influence of the use of a tape measure and a calliper on PWV values and provided equations to derive the straight D(0.8) distance from previous methodologies. PWV was measured in patients referred for ambulatory blood pressure monitoring. Carotid-femoral, carotid-sternal notch, and sternal notch-femoral distances were measured with a tape and a sliding calliper. Two hundred and fifty-nine patients (141 men and 118 women) were recruited consecutively. Their BMI ranged from 18 to 45 kg/m(2) (28.4 ± 5.0, mean ± SD). As expected, distances measured with tape were longer (3.1 ± 1.3 cm for D(0.8)) leading to higher values of PWV (0.6 ± 0.3 m/s for PWV(0.8)). This difference was similar in men and women and depended for 20% on the BMI. Equations explaining more than 85% of variance can be used to convert tape carotid-femoral, carotid-sternal notch, and tape sternal notch-femoral distances to D(0.8). It is crucial to use a sliding calliper to assess distances for PWV measurement. The overestimation with flexible tape depends on the BMI but not on the sex. Conversion equations between previous methods and the D(0.8) method can be used.


Effects of application site and subject demographics on the pharmacokinetics of fentanyl HCl patient-controlled transdermal system (PCTS).
The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, needle-free system currently in development for acute pain management in a medically supervised setting. The objectives of these studies were to evaluate skin application sites for the fentanyl HCl PCTS and to evaluate the effect of patient demographics on its pharmacokinetics. The first study was a randomised, open-label, single-centre, 3-treatment, crossover study in which the fentanyl HCl PCTS was applied to the upper outer arm, lower inner arm or chest of healthy volunteers. Fentanyl 25 microg was then delivered via this system twice during the first 20 minutes of every hour for 24 hours. The pharmacokinetics of fentanyl were determined and analysed for each application site using ANOVA. The second study was a nonrandomised, nonblind, multicentre, sequential treatment study. Healthy volunteers received fentanyl HCl 40 microg via the PCTS three times during the first 30 minutes of each hour for 3 hours. After a 5- to 10-day washout period, fentanyl HCl 120 microg was administered intravenously during the first 30 minutes of each hour for 3 hours as a reference treatment. Pharmacokinetic parameters were determined for the fentanyl HCl PCTS, and results were analysed using ANOVA. Safety and tolerability were evaluated in both studies. Application of the system to the upper outer arm or chest resulted in similar maximum serum concentrations (Cmax; 1.193 and 1.176 microg/L, respectively) and areas under the serum concentration-time curve (AUC24-25; 1.033 and 1.015 microg h/L). However, both Cmax and AUC24-25 were less when the system was applied to the lower inner arm (0.859 microg/L and 0.757 microg x h/L). Subject age, bodyweight, sex and ethnicity had no significant effect on pharmacokinetic parameters. No serious adverse events were reported in either study during or after administration of the fentanyl HCl PCTS. Fentanyl HCl is comparably absorbed from the PCTS when it is applied to the upper outer arm or chest. The pharmacokinetics of fentanyl HCl delivered by the PCTS are unaffected by sex, age, race or weight.


A limited restraint harness for use in long-term infusion of chickens.
A limited restraint harness was developed which permits long-term infusion of chickens under near normal conditions. The harness allows the birds to stand, sit, move forward and backward, and turn 180 degrees in either direction without twisting the cannula.


Three human cell surface antigen systems determined by genes on chromosome 12.
The mouse monoclonal antibodies AbA123, AbA127, AbK152, AbM68, and AbV1 were derived after immunization with cultured human tumor cells or melanocytes. Antibodies AbA123, AbA127, and AbK152 recognize human cell surface antigens expressed on most cultured human cells and show an identical pattern when tested on a panel of 47 human cell lines. They recognize at least two different epitopes on the same glycoprotein complex, designated A123/A127, which consists of 30,000-and 40,000-mol-wt glycopeptides. Antigens M68 and V1 are also expressed on most cultured human cell types but show distinct patterns of distribution on the cell line panel. The antigens defined by AbM68 and AbV1 have the characteristics of glycolipids. They are heat stable, and immunoprecipitation of metabolically labeled cell lysates did not yield any detectable components when analyzed by SDS-polyacrylamide gel electrophoresis. Serological typing of a panel of 23 independently derived mouse-human and Chinese hamster-human somatic cell hybrids showed unequivocally that the expression of cell surface antigens A123/A127, M68, and V1 segregates with human chromosome 12. The analysis of hybrids containing karyotypically defined deletions of chromosome 12 permitted the assignment of the loci determining the expression of antigens. A123/A127 and V1 to region 12cen-qter, and the locus determining the expression of antigen M68 to region 12cen-pter. These antigens can be distinguished from the cell surface molecules previously assigned to chromosome 12 and thus represent new assignments to this chromosome.


Safe use of metal-contaminated agricultural land by cultivation of energy maize (Zea mays).
Production of food crops on trace element-contaminated agricultural lands in the Campine region (Belgium) can be problematic as legal threshold values for safe use of these crops can be exceeded. Conventional sanitation of vast areas is too expensive and alternatives need to be investigated. Zea mays on a trace element-contaminated soil in the region showed an average yield of 53 ± 10 Mg fresh or 20 ± 3 Mg dry biomass ha(-1). Whole plant Cd concentrations complied with legal threshold values for animal feed. Moreover, threshold values for use in anaerobic digestion were met. Biogas production potential did not differ between maize grown on contaminated and non-contaminated soils. Results suggested favorable perspectives for farmers to generate non-food crops profitably, although effective soil cleaning would be very slow. This demonstrates that a valuable and sustainable alternative use can be generated for moderately contaminated soils on which conventional agriculture is impaired.


Ferric iron stimulation in marine SMFCs: Impact on the microbial structure evolution in contaminated sediments with low and high molecular weight PAHs.
The impact of ferric iron stimulation on the evolution of microbial structure in marine sediment microbial fuel cells (SMFCs), operated for the bioremediation of a complex mixture of low and high molecular weight PAHs (naphthalene, fluorene, pyrene and benzo(a)pyrene), was assessed. Microbial evolution profiles showed high relative abundances of exoelectrogenic iron-reducing bacteria throughout the biodegradation, namely Geoalkalibacter, under ferric iron stimulation and anode reducing conditions, irrespective of sulfate reducing bacteria (SRB) inhibition. Highest PAHs removal was measured in the absence of anode reduction, under Fe stimulation and SRB inhibition, reaching 40.85% for benzo(a)pyrene, the most persistent PAH used in this study. Results suggest that amendment of contaminated sediment with ferric iron could constitute a better bioremediation strategy than using SMFCs. This becomes significant when considering the well-established and dominant indigenous SRB population in marine sediments that usually limits the performance of the anode as a terminal electron acceptor in marine SMFCs.


Mass-spectrometry-based method for screening of new peptide ligands for G-protein-coupled receptors.
G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane proteins. Although implicated in almost all physiological processes in the human body, most of them remain unexploited, mostly because of the lack of specific ligands. The objective of this work is to develop a new mass-spectrometry-based technique capable of identifying new peptide ligands for GPCRs. The strategy is based on the incubation of cellular membranes overexpressing GPCRs with a mixture of peptides that contains potential ligands. Peptide ligands bind to the receptors, whereas other peptides remain in the binding buffer. Bound peptides are eluted from membranes and directly detected, identified, and characterized by MALDI TOF-TOF. The results reveal the efficacy of the procedure for selecting a specific ligand of GPCRs in both simple and complex mixtures of peptides. This new approach may offer direct purification, identification, and characterization of the new ligand in a single workflow. The proposed method is labeling-free and, unlike radio-binding and other techniques, it does not require a previously known labeled ligand of the studied GPCR. All these properties greatly reduce the experimental constraints. Moreover, because it is not based on the principle of a competitive specific binding, this technique constitutes a new tool to discover new ligands not only for known GPCRs, but also for orphan GPCRs.


Refractive Results Using a New Optical Biometry Device: Comparison With Ultrasound Biometry Data.
The aim of the study was to compare the measurements of optical (AL-Scan; Nidek Co., Ltd.) and ultrasonic (Echo Scan US-800; Nidek Co., Ltd.) biometry devices and to assess refractive results after cataract surgery. Eighty-one cataractous eyes of 81 patients were included in this study. Biometry was performed using the AL-Scan and an ultrasonic biometer (USB). Axial length (AL), keratometry (K) data, and intraocular lens (IOL) power calculations using the SRK/T formula were compared. Bland-Altman analysis was used to assess the extent of agreement between AL-Scan and USB data in terms of AL measurement and IOL power calculation. The K measurements of the AL-Scan were compared to autorefractor data (Canon Autorefractor RK-F1). The AL-Scan assessed the AL as longer (average difference 0.06 ± 0.18 mm; ICC = 0.987; P < 0.001) and the IOL power as greater (average difference 0.19 ± 0.66 D; ICC = 0.964; P < 0.001) than the USB. The AL-Scan also measured average K values (average difference 0.25 ± 0.25 D; ICC = 0.985; P < 0.001) greater than those given by the autorefractor. The postoperative mean absolute error was +0.30 ± 0.04 D (minimum: -0.51 D, maximum +1.04 D). The postoperative mean K value change was 0.36 ± 0.29 D (P < 0.05). The differences between measurements afforded by the AL-Scan and USB may be clinically acceptable. Keratometric changes that develop after cataract operations compromise the attainment of good refractive outcomes.


Activation of lysosomal enzymes and tumour regression caused by irradiation and steroid hormones.
The lysosomal enzyme activity and membrane permeability of mouse C3H mammary tumours has been studied using quantitative cytochemical methods following irradiation of the tumours with doses of 1500, 3500 or 6000 rad gamma rays. No change in the lysosomal enzyme activity was observed immediately after irradiation, but increased enzyme activity and increased membrane permeability were observed 24 hr after irradiation with doses of 3500 or 6000 rad. Twenty-four hours after injection of prednisolone there was a marked increase of lysosomal membrane permeability and enzyme activity, and injection of prednisolone soon after irradiation enhanced the effect of irradiation. After a dose of 6000 rad and prednisolone, the lysosomal membrane permeability increased to 191% of the control and the enzyme activity to 326% of the value of the controlled tumours. Measurement of tumour size after irradiation or after a combined treatment with irradiation and prednisolone showed that a close correlation exists between tumours regression and lysosomal enzyme activity. The experiments support the view that lysosomal enzymes play an important role in tumour regression following irradiation.


SAHA Capture Compound--a novel tool for the profiling of histone deacetylases and the identification of additional vorinostat binders.
Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC) inhibitor. Inhibitors of HDACs are used in cancer therapy based on the role HDACs play in transcription by regulating chromatin compaction and non-histone proteins such as transcription factors. Profiling of HDAC expression is of interest in the functional proteomics analysis of cancer. Also, non-HDAC proteins may interact with HDAC inhibitor drugs and contribute to the drug mode of action. We here present a tool for the unbiased chemical proteomic profiling of proteins that specifically interact with SAHA. We designed and synthesized a trifunctional Capture Compound containing SAHA as selectivity and identified HDACs1, 2, 3 and 6, known and predicted HDAC interactors from human-derived HepG2 cell lysate, as well as a set of new potential non-HDAC targets of SAHA. One of these non-HDAC targets, isochorismatase domain-containing protein 2 (ISOC2) is putative hydrolase associated with the negative regulation of the tumor-suppressor p16(INK4a). We demonstrated the direct and dose-dependent interaction of SAHA to the purified recombinant ISOC2 protein. Using SAHA Capture Compound mass spectrometry, we thus identified potential new SAHA target proteins in an entirely unbiased chemical proteomics approach.


Laser Doppler flowmetry in evaluation of colonic blood flow during aortic reconstruction.
Intraoperative laser Doppler flowmetry (LDF) was used to measure blood perfusion in terminal ileum and sigmoid colon in eight patients operated on for aorto-iliac occlusive disease (AIO) and eight patients for abdominal aortic aneurysm (AAA). The aim of the study was to evaluate the influence of clamping the inferior mesenteric artery (IMA) on intestinal perfusion. LDF-measured sigmoid colon flow was also compared with the postoperative clinical course, to define a limit below which risk of ischaemic colitis is high and revascularisation should be considered. Neither clamping of the IMA nor aortic reconstruction affected perfusion in the terminal ileum in any group. Sigmoid colon perfusion in the AAA-group showed a slight, not significant reduction after reconstruction (P = 0.09). AIO patients showed significant flow reduction in the sigmoid colon when the IMA was clamped (P less than 0.05), returning to the initial value after aortic reconstruction with end-to-side proximal anastomosis and preservation of IMA. AAA patients, operated with end-to-end proximal anastomosis and ligation of IMA, had significantly lower sigmoid colon perfusion after aortic reconstruction than AIO patients (P less than 0.05). Thirteen patients had sigmoid colon flux values greater than 5 RFU (Relative Flux Units) after reconstruction, and had no complications. Three aneurysm patients had flux values less than 3.3 RFU, and developed symptoms of ischaemic colitis. We conclude that LDF can be easily applied to the evaluation of colonic blood flow during aortic surgery. Flux values less than 4 RFU may indicate a risk of ischaemic colitis, and justify revascularisation of the colon.


An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model.
Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources.


Discovery of widespread GTP-binding motifs in genomic DNA and RNA.
Biological RNAs that bind small molecules have been implicated in a variety of regulatory and catalytic processes. Inspired by these examples, we used in vitro selection to search a pool of genome-encoded RNA fragments for naturally occurring GTP aptamers. Several aptamer classes were identified, including one (the "G motif") with a G-quadruplex structure. Further analysis revealed that most RNA and DNA G-quadruplexes bind GTP. The G motif is abundant in eukaryotes, and the human genome contains ~75,000 examples with dissociation constants comparable to the GTP concentration of a eukaryotic cell (~300 μM). G-quadruplexes play roles in diverse cellular processes, and our findings raise the possibility that GTP may play a role in the function of these elements. Consistent with this possibility, the sequence requirements of several classes of regulatory G-quadruplexes parallel those of GTP binding.


Negative linear compressibility in Se at ultra-high pressure above 120 GPa.
A series of in situ synchrotron X-ray diffraction (XRD) measurements were carried out, combined with first-principles calculations, to study structural phase transitions of selenium at high pressures and room temperature. Several phase transitions were observed, among which an isostructural phase transition was found at around 120 GPa for the first time. Evolved from the rhombohedral (space group R 3 m) structure (Se-V), the new phase (Se-V') exhibited an interesting increase of lattice parameter a at pressures from 120 to 148 GPa, known as negative linear compressibility (NLC). The discovery of NLC behavior observed in this work is mainly attributed to the accuracy and fine steps controlled by the membrane system for in situ XRD data collected with an exposure time of 0.5 s. After 140 GPa, a body-centered cubic (b.c.c.) structure Se-VI (space group Im 3 m) was formed, which remains stable up to 210 GPa, the highest pressure achieved in this study. The bulk moduli of phases Se-V, Se-V' and Se-VI were estimated to be 83 ± 2, 321 ± 2 and 266 ± 7 GPa, respectively, according to the P-V curve fit by the third-order Birch-Murnaghan equation of state. The Se-V' phase shows a bulk modulus almost 4 times larger than that of the Se-V phase, which is mainly due to the effect of its NLC. NLC in a higher pressure range is always more significant in terms of fundamental mechanism and new materials discovery, yet it has barely been reported at pressures above 100 GPa. This will hopefully inspire future studies on potential NLC behaviors in other materials at ultra-high pressure.


Prognostic value of proliferating cell nuclear antigen immunostaining in pediatric rhabdomyosarcomas.
The levels of proliferating cell nuclear antigen (PCNA) are almost negligible in long-term quiescent cells and increase dramatically during the cell cycle. Recently, the monoclonal antibodies to PCNA have been used to demonstrate the proliferative component of paraffin-embedded tumor tissues. It has been shown to be available as a simple histological marker of proliferative activity and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin fixed, paraffin embedded tissue specimens of 29 primary pediatric rhabdomyosarcomas were immunostained by using an anti-PCNA monoclonal antibody (DAKO PCNA PC10). The relationship between the PCNA index and prognosis, clinicopathological features and survival were assessed retrospectively. The mean PCNA index for the whole series was 54%. There was no correlation between PCNA index and any of the clinicopathological characteristics. However, patients having tumors with a high (> 54%) PCNA index demonstrated significantly lower survival rates than tumors with a low (< 54%) PCNA index (P = 0.01). Moreover, there were significantly more patients with relapse or progressive disease in the high PCNA index group (P = 0.005). The PCNA labeling index can be a useful prognostic factor and a good indicator of recurrence and/or survival in patients with rhabdomyosarcoma.


An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance.
Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of virus-infected cells. For convenience, this new assay was named IRINA (Influenza Replication Inhibition Neuraminidase-based Assay). IRINA was successfully validated to assess inhibitory activity of baloxavir on virus replication by testing a large set (>150) of influenza A and B viruses, including drug resistant strains and viruses collected during 2017-2022. To test its versatility, IRINA was utilized to evaluate neutralization activity of a broadly reactive human anti-HA monoclonal antibody, FI6, and post-infection ferret antisera, as well as the inhibition of NA enzyme activity by NA inhibitors. Performance of IRINA was tested in parallel using respective conventional assays. IRINA offers an attractive alternative to current phenotypic assays, while maintaining reproducibility and high throughput capacity. Additionally, the improved turnaround time may prove to be advantageous when conducting time sensitive studies, such as investigating a new virus outbreak. This assay can meet the needs of surveillance laboratories by providing a streamlined and cost-effective approach for virus characterization.


[Evolution of the incidence and survival of bronchogenic carcinoma in the province of Castellón (Spain) from 2004 to 2017.]
Bronchogenic carcinoma (BC) is the second most frequent worldwide and the most lethal tumour in both sexes. Its incidence varies not only among countries but also among different areas of the same country. So, the aim of this work was to analyse the evolution of its incidence and survival in the province of Castellón from 2004 to 2017 and to compare them with those of de rest of the country. A retrospective observational study was carried out from patients diagnosed with BC and registered in the Castellón Tumour Register from 2004 to 2017. Survival was estimated using the Kaplan-Meier method whereas to estimate the relationship among different variables both the chi-square and ANOVA test were used. 4,346 cases were diagnosed, whose mean age was 67.5±11.3 years, 85.2% men, the most frequent histological types were adenocarcinoma (28.3%) and epidermoid carcinoma (25.1%). The gross global incidence was 53.4 cases/105 inhabitants, 90.9 cases/105 men and 15.7 cases/105 women. Median global survival at five years was 12.7%, 12% in men and 18.4% in women. The global incidence of BC in Castellón is lower than the national one, having remained stable in men while it is double in women. Global survival at five years is less than 15%, being higher in women than in men, nevertheless it increases compared to that of previous studies.


Large coefficient of variation of inter-spike intervals induced by noise current in the resonate-and-fire model neuron.
Neuronal spike variability is a statistical property associated with the noise environment. Considering a linearised Hodgkin-Huxley model, we investigate how large spike variability can be induced in a typical stellate cell when submitted to constant and noise current amplitudes. For low noise current, we observe only periodic firing (active) or silence activities. For intermediate noise values, in addition to only active or inactive periods, we also identify a single transition from an initial spike-train (active) to silence dynamics over time, where the spike variability is low. However, for high noise current, we find intermittent active and silence periods with different values. The spike intervals during active and silent states follow the exponential distribution, which is similar to the Poisson process. For non-maximal noise current, we observe the highest values of inter-spike variability. Our results suggest sub-threshold oscillations as a possible mechanism for the appearance of high spike variability in a single neuron due to noise currents.


Attending to hidden realities: contributions from the work of Michael Polanyi to supervision in pastoral care and counseling.
In this article, the author suggests that concepts from the work of Michael Polanyi--such as the tacit dimension, subsidiary awareness, and commitment to a yet unrevealed, hidden reality--provide a theoretical basis for understanding the unique formation involved in pastoral care and counseling supervision.


Sexual dysfunction in the diabetic patient with hypertension.
The prevalence of diabetes mellitus and hypertension in the United States is increasing partly because of the incidence of these diseases in the growing geriatric population. Diabetes and hypertension have been associated with sexual dysfunction in both men and women. Neuropathy, vascular insufficiency and psychological problems have been implicated in impotence, impaired ejaculation and decreased libido in men and in decreased vaginal lubrication, orgasmic dysfunction and decreased libido in women. Several investigations of women with diabetes suggest fewer reports of sexual dysfunction than have been reported by diabetic men. However, there have been few evaluations of sexual dysfunction in women and no standard methods for assessment. Antihypertensive agents, especially diuretics, sympathetic inhibitors and beta-blocking agents have been associated with sexual dysfunction due to autonomic and hormonal effects. An estimated 40 to 80% of diabetic hypertensives have reported sexual dysfunction in several investigations. Clearly, the diabetic hypertensive patient should be evaluated for sexual dysfunction, and appropriate therapy, including changes in medication or referral for sex counseling, should become routine in clinical care.


The effect of several different anaesthetics on the blood pressure and heart rate of the mouse and on the radiation response of the mouse sarcoma RIF-1.
Several anaesthetics were tested with mice to study: (a) their ability to immobilize the animal; (b) their effect on blood pressure and heart rate; and (c) their effect on the response to X-irradiation of the mouse sarcoma RIF-1. All anaesthetics which produced adequate immobilization also caused a fall in blood pressure and some radioprotection of tumour cells. Physical restraint of the tumour-bearing leg of an unanaesthetized mouse also caused radioprotection of the tumour cells.


Pseudoaneurysm of the inferior medial geniculate artery following primary total knee arthroplasty: delayed presentation with recurrent haemorrhagic episodes.
Arterial complications in primary total knee arthroplasty operation are rare. An 83 year old lady is described who presented with three recurrent haemorrhagic episodes eroding through the medial skin 4 weeks following primary total knee arthroplasty. A pseudoaneurysm of the geniculate artery should be suspected with recurrent or persistent haemarthrosis/haemorrhagic episodes. Early exploration, evacuation of the aneurysmal cavity and ligation of the feeding vessel should be undertaken if the false aneurysm is large in diameter.


Bis-(3-methyl-1-propyl-1,3-di-hydro-1H-imidazol-2-yl-idene)silver(I) chlor-ido(5,10,15,20-tetra-phenyl-porphin-ato)cadmate(II).
The structure of the title salt, [Ag(C7H12N2)2][CdCl(C44H28N4)], at 150 K has triclinic symmetry. One of the phenyl rings bonded to the porphyrin mol-ecule and the propyl groups of both yl-idene mol-ecules coordinating to silver are disordered over two positions.


Histochemical studies of some myocardial oxido-reductive enzymes after experimental beta-adrenergic blockade with propranolol.
Histochemical studies of some myocardial oxido--reductive enzymes after a beta--adrenergic blockade with propranolol have been carried out. Succinate, isocitrate and glucose-6-phosphate dehydrogenases did not indicate any changes in activity, whereas the changes in reaction intensities concerning NADH and NADPH tetrazole reductases and glutamate dehydrogenase have rather a transitory and reversible character. Only lactate dehydrogenase showed an increase in the enzymatic activity which speaks for an increase in the glycolysis process in the heart muscle. In the light of our own presented research results we assume that the experimental beta--adrenergic blockade of the heart muscle in rats does not evoke more important enzymatic changes which are noticeable in histochemical microscope examination.


Atmospheric pressure photoionization as a powerful tool for large-scale lipidomic studies.
Lipidomic studies often use liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) for separation, identification, and quantification. However, due to the wide structural diversity of lipids, the most apolar part of the lipidome is often detected with low sensitivity in ESI. Atmospheric pressure (APPI) can be an alternative ionization source since normal-phase solvents are known to enhance photoionization of these classes. In this paper, we intend to show the efficiency of APPI to identify different lipid classes, with a special interest on sphingolipids. In-source APPI fragmentation appears to be an added value for the structural analysis of lipids. It provides a detailed characterization of both the polar head and the non polar moiety of most lipid classes, and it makes possible the detection of all lipids in both polarities, which is not always possible with ESI.


Estimating the genome-wide contribution of selection to temporal allele frequency change.
Rapid phenotypic adaptation is often observed in natural populations and selection experiments. However, detecting the genome-wide impact of this selection is difficult since adaptation often proceeds from standing variation and selection on polygenic traits, both of which may leave faint genomic signals indistinguishable from a noisy background of genetic drift. One promising signal comes from the genome-wide covariance between allele frequency changes observable from temporal genomic data (e.g., evolve-and-resequence studies). These temporal covariances reflect how heritable fitness variation in the population leads changes in allele frequencies at one time point to be predictive of the changes at later time points, as alleles are indirectly selected due to remaining associations with selected alleles. Since genetic drift does not lead to temporal covariance, we can use these covariances to estimate what fraction of the variation in allele frequency change through time is driven by linked selection. Here, we reanalyze three selection experiments to quantify the effects of linked selection over short timescales using covariance among time points and across replicates. We estimate that at least 17 to 37% of allele frequency change is driven by selection in these experiments. Against this background of positive genome-wide temporal covariances, we also identify signals of negative temporal covariance corresponding to reversals in the direction of selection for a reasonable proportion of loci over the time course of a selection experiment. Overall, we find that in the three studies we analyzed, linked selection has a large impact on short-term allele frequency dynamics that is readily distinguishable from genetic drift.


Environmental hazards associated with open-beach breaking of end-of-life ships: a review.
End-of-life (EOL) ships contribute significantly to the flow of recycled industrial Fe and non-Fe metal materials in resource-poor developing countries. The ship scrapping (breaking) and recycling industry (SBRI) recycles 90-95% of the total weight of EOL ships and is currently concentrated in Bangladesh, India, Pakistan, Turkey, and China, due to the high demand for recyclable and reusable materials there, an abundance of low-cost labor, and lenient environmental regulations. However, the SBRI has long been criticized for non-compliance with standards relating to occupational health, labor safety, and to the management of hazardous materials. Among the different EOL recycling options, Bangladesh, India, and Pakistan use open beaching, a technique that exposes all spheres of the environment to the release of hazardous materials from EOL ships. This article summarizes the current state of knowledge on the environmental exposure of hazardous materials from SBRI, to judge the risks associated with the dismantling of EOL ships on open beaches. Our work includes an overview of the industry and its recent growth, compares available ship-breaking methods, provides an inventory of hazardous releases from EOL ships, and reviews their movement into different spheres of the environment. The economic dynamics behind open beaching, and apportionment of responsibility for hazards related to it, are discussed, in order to generate policy and legal recommendations to mitigate the environmental harm stemming from this industry.


The role of PML in tumor suppression.
The PML gene, involved in the t(15;17) chromosomal translocation of acute promyelocytic leukemia (APL), encodes a protein which localizes to the PML-nuclear body, a subnuclear macromolecular structure. PML controls apoptosis, cell proliferation, and senescence. Here, we review the current understanding of its role in tumor suppression.


Use of intercellular washing fluid to investigate the secreted proteome of the rice-Magnaporthe interaction.
Early interactions between invading penetration hyphae of the pathogenic fungus Magnaporthe oryzae and rice cells occur at the apoplast, the free diffusional space outside the plasma membrane of leaves. After initial colonization, intercellular hyphae are again in intimate contact with the rice apoplast. While several studies have looked at proteomics in rice-Magnaporthe interactions, none have focused on apoplast localized proteins. We adjusted a protocol for intercellular washing fluids (IWF) to rice leaves infected with Magnaporthe oryzae for proteomic analysis. In our IWF extract, we identified several proteins associated with compatible or incompatible pathogen interactions. Three DUF26 domain proteins were identified as changing in abundance 12 h after inoculation, confirming DUF26 domain-containing proteins are among early, pathogen stress-responsive proteins induced by infection with Magnaporthe oryzae. A Magnaporthe cyclophilin, previously identified as a virulence factor was also identified in the intercellular washing fluid.


Distinct associations between dietary omega-3 and omega-6 fatty acids intake with chronic kidney disease in adults with and without diabetes: A cross-sectional study.
We explored the relationship of dietary intake of fatty acids with chronic kidney disease (CKD) according to glycemic status in Japanese people. A total of 1031 participants aged ≥40 y were included in this population-based, cross-sectional study. A validated self-administered diet history questionnaire was used to measure the dietary intakes of fat and fatty acids, including omega-3 and omega-6 polyunsaturated fatty acids. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and diabetes as the use of antidiabetic medication, fasting plasma glucose ≥ 126 mg/dL, or hemoglobin A1c of ≥6.5%. Urine biomarkers of kidney injury (liver-type fatty acid-binding protein, β2-microglobulin, and albumin) were also examined. The mean age of the participants was 62.5 ± 11.2 y, and 482 (46.8%) of them were men. Overall, 177 (17.2%) participants had CKD. In the multivariable model, low omega-3 intake (odds ratio = 0.109; 95% CI, 0.019-0.645) and high omega-6-to-omega-3 ratio (odds ratio = 2.112; 95% CI, 1.167-3.822) were associated with CKD in participants with diabetes but not in those without. In selected participants with diabetes, a substantial trend of urinary liver-type fatty acid-binding protein and β2-microglobulin level elevation along with an increase in the dietary ratio of omega-6 to omega-3 was observed. Low dietary omega-3 intake and high omega-6-to-omega-3 ratio were associated with CKD in middle-aged and older Japanese people with diabetes but not in those without diabetes. These results may provide insight into the more tailored approaches for dietary polyunsaturated fatty acids to prevent CKD.


Details of local dispersion improve the fit of neighborhood competition models.
I performed a series of greenhouse experiments to explore how patterns in the dispersion of local competitors affect the reproductive performance of Capsella bursa-pastoris, Poa annua and Senecio vulgaris. I manipulated the density and relative frequency of competitors in each of three concentric rings surrounding a central plant, thereby creating a variety patterns by which local competitors were distributed. Neighborhood competition models were used to predict the seed output of these central plants. For both Senecio vulgaris and Capsella bursa-pastoris, I found that models which incorporated the dispersion of competitors, as well as the relative emergence date of plants, performed substantially better than those that considered only the distance between the central plant and each of its competitors. I was unable to measure the seed output of Poa annua but neither emergence data nor the dispersion of competitors were important in determining its final dry-weight.


Allelic variations in superoxide dismutase-1 (SOD1) gene are associated with increased risk of diabetic nephropathy in type 1 diabetic subjects.
Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and have a protective effect against diabetic nephropathy. We investigated associations of allelic variations in SOD1 gene with nephropathy in patients with type 1 diabetes. Seven SNPs in SOD1 region were analyzed in 1285 type 1 European Caucasian diabetic patients from the SURGENE prospective study (n=340; ten year follow-up), and the Genesis France-Belgium (n=501) and GENEDIAB (n=444) cross-sectional studies. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios or odds ratios for incidence and prevalence of diabetic nephropathy. In the SURGENE study, the T-allele of rs1041740 was associated with the prevalence of incipient (OR 5.75, 95% CI 1.78-19.39, p=0.004) and established/advanced nephropathy at baseline (OR 8.95, 95% CI 1.51-58.42, p=0.02), and with the incidence of incipient nephropathy during follow-up (HR 1.46, 95% C.I. 1.13-1.90, p=0.004). The variant was also associated with decreased estimated glomerular filtration rate (eGFR) throughout the study. In cross-sectional study of Genesis/GENEDIAB cohorts, the G-allele of rs17880135 was associated with incipient (OR 7.53, 95% CI 2.30-25.45, p=0.001), established (OR 6.04, 95% CI 1.52-23.91, p=0.01) and advanced nephropathy (OR 10.03, 95% CI 2.95-35.44, p=0.0003). SOD1 allelic variations were associated with the prevalence of diabetic nephropathy, with the incidence of microalbuminuria and with decreased eGFR in type 1 diabetic subjects. These results are consistent with an implication of oxidative stress in the pathophysiology of diabetic nephropathy and with the major role for antioxidant enzymes as a mechanism of renal protection.


Impacts of the phenylpyrazole insecticide fipronil on larval fish: time-series gene transcription responses in fathead minnow (Pimephales promelas) following short-term exposure.
The utilization of molecular endpoints in ecotoxicology can provide rapid and valuable information on immediate organismal responses to chemical stressors and is increasingly used for mechanistic interpretation of effects at higher levels of biological organization. This study contributes knowledge on the sublethal effects of a commonly used insecticide, the phenylpyrazole fipronil, on larval fathead minnow (Pimephales promelas), utilizing a quantitative transcriptomic approach. Immediately after 24h of exposure to fipronil concentrations of ≥31 μg.L(-1), highly significant changes in gene transcription were observed for aspartoacylase, metallothionein, glucocorticoid receptor, cytochrome P450 3A126 and vitellogenin. Different mechanisms of toxicity were apparent over the course of the experiment, with short-term responses indicating neurotoxic effects. After 6 days of recovery, endocrine effects were observed with vitellogenin being up-regulated 90-fold at 61 μg.L(-1) fipronil. Principal component analysis demonstrated a significant increase in gene transcription changes over time and during the recovery period. In conclusion, multiple mechanisms of action were observed in response to fipronil exposure, and unknown delayed effects would have been missed if transcriptomic responses had only been measured at a single time-point. These challenges can be overcome by the inclusion of multiple endpoints and delayed effects in experimental designs.


Icariin induces apoptosis of human lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway.
Lung cancer is the largest cause of morbidity and mortality among tumor diseases. Traditional first-line chemotherapeutic drugs are frequently accompanied by serious side effects when used to treat tumors, thus, novel drugs with reduced toxic effects may improve a patients' quality of life. Icariin, an extract of herba epimedii, has been demonstrated to exhibit multiple antitumor effects with low toxicity. In the present study, cell cycle analysis, apoptosis assays, DAPI staining, CCK8 assays, xenograft tumor models, mitochondrial membrane potential analysis, western blotting and reverse transcription-quantitative PCR were performed to determine the molecular mechanism underlying icariin activity in the human lung adenocarcinoma cell lines, A549 and H1975. The results showed that icariin reduced proliferation of A549 and H1975 cells in a time- and dose-dependent manner in vitro to a greater degree than the control BEAS-2B cells, and this was associated with increased apoptosis, but not with cell cycle progression. In vivo experiments showed that icariin treatment significantly decreased proliferation of H1975 cells in a xenograft mouse model. Mechanistically, icariin activated the mitochondrial pathway by inhibiting the activation of the PI3K-Akt pathway-associated kinase, Akt, resulting in the activation of members of the caspase family of proteins, and thus inducing apoptosis of A549 cells. Taken together, the results revealed that icariin has anti-cancer properties in lung cancer in vitro and in vivo without any noticeable toxic effects on normal lung epithelial cells. Icariin in combination with conventional anti-cancer agents may be an effective therapeutic strategy for treatment of lung carcinoma.


The effect of liposomal incorporation of topically applied hydrocortisone on its serum concentration and urinary excretion.
We demonstrated previously, that hydrocortisone incorporated in the phospholipid bilayer of liposomes (liposomal hydrocortisone) shows an improved concentration-time profile in the different skin layers after external application when compared with a conventional ointment. In the present work, it was investigated under in vivo conditions, whether or not the liposomal formulation also enhances the percutaneous absorption rate. The results obtained in guinea pigs clearly demonstrate a decrease in serum concentration and urinary excretion. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system or "drug localizer" increasing the therapeutic efficacy and, simultaneously, decreasing adverse systemic effects. The significance of liposomal attenuative and potent glucocorticoids in topical treatment is discussed.


How people wake up is associated with previous night's sleep together with physical activity and food intake.
How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual's set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable.


Primary Care Provider Demographics and Engagement in Interprofessional Collaboration.
Interprofessional care contributes to all components of the quadruple aim. While previous research has identified many facilitators and barriers to the provision of interprofessional care, whether demographic differences might influence the extent to which providers collaborate interprofessionally remains unknown. Using electronic health record data, we characterized the level of primary care providers' (PCPs') interprofessional collaboration based on the percent of their patients who had a visit with an interprofessional team member over a 14-month period. We then obtained demographic data, including gender, years in practice, and provider type, from the electronic health record and publicly available sources. Subsequently, we used linear regression to predict the PCPs' level of interprofessional collaboration based on demographic indicators. The median of each PCP's patients who had a visit with an interprofessional team member during the study period was 12.6%. After controlling for the average age of the PCP's patient panel, the PCP's years in practice, and the PCP's clinic, when compared with male PCPs, approximately 2% more of patients cared for by female PCPs had a visit with an interprofessional team member. Female providers are more likely to share their patients with an interprofessional team.


Bioinformatics identification of antigenic peptide: predicting the specificity of major MHC class I and II pathway players.
Bioinformatics methods for immunology have become increasingly used over the last decade and now form an integrated part of most epitope discovery projects. This wide usage has led to the confusion of defining which of the many methods to use for what problems. In this chapter, an overview is given focusing on the suite of tools developed at the Technical University of Denmark.


Predisposing factors for surgical site infection of spinal instrumentation surgery for diabetes patients.
Diabetes mellitus (DM) is known as an important risk factor for surgical site infection (SSI) in spine surgery. It is still unclear however which DM-related parameters have stronger influence on SSI. The purpose of this study is to determine predisposing factors for SSI following spinal instrumentation surgery for patients with DM. 110 DM patients (66 males and 44 females) who underwent spinal instrumentation surgery in one institute were enrolled in this study. For each patient, various preoperative or intraoperative parameters were reviewed from medical records. Patients were divided into two groups (SSI or non-SSI) based on the postoperative course. Each parameter between these two groups was compared. Univariate and multivariate analyses were performed to determine predisposing factor for SSI. The SSI group consisted of 11 patients (10%), and the non-SSI group of 99 patients (90%). Univariate analysis revealed that preoperative proteinuria (p = 0.01), operation time (p = 0.04) and estimated blood loss (p = 0.02) were significantly higher in the SSI group compared to the non-SSI group. Multivariate logistic regression identified preoperative proteinuria as a statistically significant predictor of SSI (OR 6.28, 95% CI 1.58-25.0, p = 0.009). Proteinuria is a significant predisposing factor for SSI in spinal instrumentation surgery for DM patients. DM patients with proteinuria who are likely to suffer latent nephropathy have a potential risk for SSI. For them less invasive surgery is recommended for spinal instrumentation. In this retrospective study, there was no significant difference of preoperative condition in glycemic control between the two groups.


Optimization of the preparation of fungal-algal pellets for use in the remediation of arsenic-contaminated water.
This study was conducted to optimize the preparation of fungal-algal pellets for use in the removal of arsenite (As(III)) and arsenate (As(V)) from water. Three parameters, i.e., glucose concentration, shaking speed, and pH, were investigated to show their effects on the immobilization efficiency of algal biomass attached to fungal mycelial pellets. The highest immobilization efficiency was achieved at 5 g glucose L-1, 140 rpm, and pH 7. Furthermore, the fungal-algal pellets with different initial algal biomass were tested regarding the stability and their capability of removing As(III) and As(V). The fungal-algal pellets could not keep good stability when the initial algal biomass was more than 4.8 × 107 cells mL-1. The highest removal rates of As(III) and As(V) were obtained by the fungal-algal pellets with initial algal biomass of 4.8 × 107 cells mL-1, and the removal rate of As(V) was much higher compared with that of As(III). Similar trends were observed for the concentrations of total arsenic as well as As(III) and As(V) in fungal-algal pellets. The fungal-algal pellets with initial algal biomass of 4.8 × 107 cells mL-1 showed a significant potential for removing As(V) from water, and microalgae might play a key role in the absorption and transformation of inorganic arsenic. Adsorption kinetics studies suggested that the adsorption of As(V) onto fungal-algal pellets followed the pseudo-second-order kinetic model, and the pseudo-first-order kinetic model was more appropriate for describing the adsorption of As(III).


Activity of pivaloyloxymethyl butyrate, a novel anticancer agent, on primary human tumor colony-forming units.
The anti-proliferative effects of pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) derivative with potent tumor-differentiating properties both in vitro and in vivo, was evaluated against colorectal, breast, lung, ovarian, renal cell, bladder, and other types of tumor colony-forming units in a human tumor cloning assay. A total of 76 evaluable specimens were exposed to AN-9 continuously, 48 of these were also exposed to BA continuously for direct comparison of the two agents, and 20 specimens were exposed to AN-9 for two hours. An in vitro inhibitory response was defined as a > or = 50% decrease in tumor colony formation in treated cells compared to untreated controls. Superior anti-tumor activity was observed with the continuous exposure to AN-9 (39% in vitro response at 100 microM and 70% at 200 microM) than with the two-hour exposure (20% at 100 microM and 25% at 200 microM). At a continuous concentration of 200 microM, AN-9 demonstrated greater tumor-specific activity than BA against melanoma (100% vs. 67%), ovarian (67% vs. 40%), breast (63% vs. 0%), non-small cell lung (60% vs. 10%), and colorectal tumor colony-forming units (62% vs. 20%). AN-9 is a novel differentiating agent with activity against colony-forming units derived from a variety of primary human tumors, including those that are considered relatively chemoresistant, and may thus provide a therapeutic alternative or addition to standard cytotoxic agents, if appropriate drug concentrations can be achieved in patients.


6/7Li NMR study of the Li1-zNi1+zO2 phases.
A series of Li1-zNi1+zO2 materials have been synthesised by the coprecipitation route. An X-ray diffraction study was carried out on these materials using the Rietveld method to determine the departure from the ideal stoichiometry z, which ranges from 0 to 0.138. The actual Li/Ni ratio was also checked by chemical analyses using inductively coupled plasma (ICP) for each sample. The stoichiometric sample (z approximately 0) was obtained using a 15% Li excess. (6/7)Li NMR results from LiNiO2 (z approximately 0) show that the asymmetric shape of the NMR signal is due to anisotropy. Calculations give evidence that the paramagnetic dipolar interaction from the electron spins carried by Ni is anisotropic but does not completely explain the experimental anisotropy. (6)Li MAS NMR (magic angle spinning NMR) experiments and temperature standardisation NMR measurements unambiguously assign the isotropic position at +726 ppm. The static-echo NMR spectra of the non-stoichiometric Li1-zNi1+zO2 phases also exhibit an asymmetric shape whose width increases with the departure from the ideal stoichiometry z. (6/7)Li static and MAS NMR show that the 2zNi(2+) ions thus formed modify the dipolar interaction within the materials and also affect the Fermi contact interaction, since a distribution of Li environments is observed using (6)Li NMR for non-stoichiometric samples.


Localization of the novel neuropolypeptide h3 in subsets of tissues from different species.
Recently we reported the isolation and partial biochemical characterization of a novel polypeptide, h3, from the human brain and liver. Thin-layer isoelectric focusing showed that the polypeptide was ubiquitously distributed throughout the human brain. Immunophosphatase transfer electrophoresis showed that this protein was localized in several mammalian species and different tissues. In addition, h3 or h3-like protein was demonstrated in subsets of tissues from one avian species. Protein h3 was present in epithelial and muscular tissue, as well as in nervous tissue; however, for all species investigated, it was most abundant in CNS and muscle.


Occurrence and distribution of antibiotics in groundwater, surface water, and sediment in Xiong'an New Area, China, and their relationship with antibiotic resistance genes.
The emergence and pollution of antibiotics in surface water in various regions have drawn widespread concern because of the harm to aquatic ecosystems and human health. In this study, we aim to first investigate contamination and ecological risks of 39 antibiotics in Xiong'an New Area (XANA), China, and then illuminate relative abundances of antibiotic resistance genes (ARGs) and their correlations with antibiotics. The sum of antibiotic concentrations in the water circulation system, including surface water, groundwater, and sediment was 12.71-260.56 ng/L, ND-196.12 ng/L, and 38.03-406.31 ng/g, respectively. In surface water and sediment, cephalosporins and quinolones were the primary antibiotics, accounting for 45% and 16% of the total antibiotic concentrations in surface water and for 62% and 32% of the total antibiotic concentrations in sediment; this suggests a significant interaction between the two media. The antibiotic concentration was the highest in shallow groundwater at depths of <50 m (mean concentration of 79.22 ± 56.46 ng/L), indicating that surface water was a possible source of antibiotic contamination in groundwater. AMX presented the highest risk in both surface and groundwater and should be controlled as a priority. Moreover, the selection pressure of antibiotics on ARGs was discovered in the sediment in XANA, because the enrichment of sulA was significantly correlated with spiramycin and lincomycin and the enrichment of blaOXA-1 was significantly correlated with roxithromycin, ciprofloxacin, ofloxacin, and sulfapyridine. Thus, our investigation revealed potential antibiotic contamination in multiple environmental media in XANA, which should be addressed to prevent more serious pollution.


An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma.
The ability of fluorescence in situ hybridization (FISH) assays in endoscopic transpapillary bile duct biopsy specimens to predict the prognosis of cholangiocarcinoma (CCA) has not been elucidated. We aimed to clarify the association between the results of UroVysion FISH assays and the prognosis of CCA. We retrospectively reviewed 49 specimens obtained by transpapillary forceps biopsy from consecutive patients with CCA. The copy numbers of chromosomes 3, 7, and 17 were evaluated by FISH assay using UroVysion. We compared the overall survival (OS) of CCA patients with and without increased copy numbers of chromosomes 3, 7, and 17. Furthermore, we evaluated the association between OS and the clinicopathological parameters of CCA patients. The OS was significantly shorter in patients with than without an increased chromosome 7 copy number (log-rank p = 0.015; median OS 11.9 vs. 20.7 months). In the univariate analyses, age (p = 0.012), ECOG performance status (p = 0.046), tumor stage (p = 0.046), surgery (p = 0.006), and an increased chromosome 7 copy number (p = 0.017) were significantly associated with OS. The multivariate analysis revealed that an increased chromosome 7 copy number (hazard ratio, 2.46; 95% CI 1.15-5.27; p = 0.021) and advanced clinical stage (hazard ratio, 2.26; 95% CI 1.11-4.63; p = 0.025) were independently predictive of a poor OS. Detection by FISH assay of an increased chromosome 7 copy number in transpapillary forceps biopsy specimens is predictive of a poor prognosis in CCA patients.


Synthesis of metaettringite from blast furnace slag and evaluation of its boron adsorption ability.
Blast furnace slag (BFS) is generated as a by-product in the ironmaking process, and hence, the development of a recycling system for BFS waste is important. In this study, the calcium component of BFS obtained from a steel company in Japan was successfully used as raw material of the synthesis of metaettringite. Metaettringite has been recently considered for as an adsorbent for boron, which is toxic to humans and animals. The BFS used was amorphous, and mainly consisted of CaO, SiO2, Al2O3, and MgO; in particular, it contained 42.82 mass % CaO. The X-ray diffraction pattern and Fourier transform infrared spectrum of the synthesized sample indicated the formation of metaettringite. Field-emission scanning electron microscopy observations revealed its needle-like morphology. The synthesized metaettringite adsorbed 1.189 mg-B/g-adsorbent in 240 min, which was approximately 25 times greater than that achieved using the parent BFS. The metaettringite can reduce the boron concentration to below the uniform effluent standard in industrial wastewater in Japan (16 mg/L).


Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction.
Ubiquitin-immunoreactive neuronal inclusions composed of TAR DNA binding protein of 43 kDa (TDP-43) are a major pathological feature of frontotemporal lobar degeneration (FTLD-TDP). In vivo studies with TDP-43 knockout mice have suggested that TDP-43 plays a critical, although undefined role in development. In the current report, we generated transgenic mice that conditionally express wild-type human TDP-43 (hTDP-43) in the forebrain and established a paradigm to examine the sensitivity of neurons to TDP-43 overexpression at different developmental stages. Continuous TDP-43 expression during early neuronal development produced a complex phenotype, including aggregation of phospho-TDP-43, increased ubiquitin immunoreactivity, mitochondrial abnormalities, neurodegeneration and early lethality. In contrast, later induction of hTDP-43 in the forebrain of weaned mice prevented early death and mitochondrial abnormalities while yielding salient features of FTLD-TDP, including progressive neurodegeneration and ubiquitinated, phospho-TDP-43 neuronal cytoplasmic inclusions. These results suggest that neurons in the developing forebrain are extremely sensitive to TDP-43 overexpression and that timing of TDP-43 overexpression in transgenic mice must be considered when distinguishing normal roles of TDP-43, particularly as they relate to development, from its pathogenic role in FTLD-TDP and other TDP-43 proteinopathies. Finally, our adult induction of hTDP-43 strategy provides a mouse model that develops critical pathological features that are directly relevant for human TDP-43 proteinopathies.


A biochemical and ultrastructural comparison of Triton X-100 models of normal and transformed cells.
We have compared the two-dimensional gel profiles of Triton models of normal rat kidney (NRK) cells and their Kirsten viral transformant, 442. Several protein differences were detected. The models of the transformed line lacked five acidic polypeptides and possessed a much higher intermediate filament to actin ratio. Scanning microscopy reveals significant ultrastructural differences in these models, with the NRK line exhibiting a much more filamentous structure. In addition, nuclease treatment of NRK models causes a dramatic change in their scanning image while the 442 models are unaffected. Nuclease treated models lack microfilaments and appear to contain only intermediate filaments, although actin is still a prominent protein constituent.


Effect of chitosan-lemon essential oil coatings on volatile profile of strawberries during storage.
Chitosan coatings containing lemon essential oils were described as effective at controlling fruit fungal decay at 20°C during 7 days. In this work, GC-MS was used to characterise the volatile compounds of strawberries during cold storage in order to analyse the influence of fruit coatings with chitosan, containing or not containing lemon essential oil, on the volatile profile of the fruits. The coatings affected the metabolic pathways and volatile profile of the fruits. Pure chitosan promoted the formation of esters and dimethyl furfural in very short time after coating, while coatings containing lemon essential oil incorporated terpenes (limonene, γ-terpinene, p-cymene and α-citral) to the fruit volatiles and enhanced the fermentative process, modifying the typical fruit aroma composition. No effect of chitosan coatings was sensorially perceived, the changes induced by lemon essential oil were notably appreciated.