A prospective algorithm for the management of air leaks after pulmonary resection.
Air leaks (ALs) are a common complication after pulmonary resection, yet there is no consensus on their management. An algorithm for the management of chest tubes (CT) and ALs was applied prospectively to 101 consecutive patients who underwent elective pulmonary resection. Air leaks were graded daily as forced expiratory only, expiratory only, inspiratory only, or continuous. All CTs were kept on 20 cm of suction until postoperative day 2 and were then converted to water seal. On postoperative day 3, if both a pneumothorax and AL were present, the CT was placed to 10 cm H2O of suction. If a pneumothorax was present without an AL, the CT was returned to 20 cm H2O of suction. Air leaks that persisted after postoperative day 7 were treated with talc slurry. There were 101 patients (67 men); on postoperative day 1, 26 had ALs and all were expiratory only. Univariable analysis showed a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (p = 0.005), increased age (p = 0.007), increased ratio of residual volume to total lung capacity (RV/TLC) (p = 0.04), increased RV (p = 0.02), and an increased functional residual capacity (FRC) (p = 0.02) to predict the presence of an AL on postoperative day 1. By postoperative day 2, 22 patients had expiratory ALs. After 12 hours of water seal, 13 of the 22 patients' ALs had stopped, and 3 more sealed by the morning of postoperative day 3. However, 2 of the 6 patients whose ALs continued experienced a pneumothorax. Five of the 6 patients with ALs on postoperative day 4 still had ALs on postoperative day 7, and all were treated by talc slurry through the CT. All ALs resolved within 24 hours after talc slurry. Most ALs after pulmonary resection are expiratory only. A low FEV1/FVC ratio, increased age, increased RV/TLC ratio, increased RV, and an increased FRC were predictors of having an ALs on postoperative day 1. Conversion from suction to water seal is an effective way of sealing expiratory AL, and pneumothorax is rare. If an expiratory AL does not stop by postoperative day 4 it will probably persist until postoperative day 7, and talc slurry may be an effective treatment.


Comparative evaluation of single and combined efficacy of dipyridamole, ketotifen and quercetin on cyclosporine induced hepatorenal toxicity.
Cyclosporine is an immunosuppressive drug that is used to prevent tissue rejection in organ transplants and to treat autoimmune diseases such as psoriasis and rheumatoid arthritis. It has important toxic effects in many organs such as the liver and kidney. The aim of this study was to determine and compare the effectiveness of the single and combined treatment of dipyridamole, which is a vasodilator and has an antioxidant effect, ketotifen which is toll-like receptor-4 inhibitory and has an antioxidant effect, quercetin which is an antioxidant and has an anti-inflammatory effect in cyclosporine-induced hepatorenal toxicity. Forty-eight Wistar Albino rats were divided into 7 groups. The research period was 21 days. The cyclosporine increased serum ALT and AST levels, in contrast to their increased levels prevented by all the treatments. The serum creatinine level decreased significantly with ketotifen and combined treatment, while cyclosporine partially increased serum creatinine and urea levels. The urine microalbumin and protein levels were increased significantly by cyclosporine, whereas they decreased with dipyridamole treatment. The protein levels decreased by quercetin and combined treatments. The kidney injury molecule- 1 and retinol-binding protein levels were increased by the cyclosporine, while ketotifen treatment partially decreased them. In conclusion, ketotifen and dipyridamole can prevent cyclosporine- induced hepatorenal toxicity and quercetin can increase the effectiveness of this treatment.


Cytomegalovirus disease in renal transplant recipients: a single-center experience.
Cytomegalovirus (CMV) disease is an important complication and an independent risk factor for acute rejection and recipient morbidity-mortality. The aim of this study was to review the results of CMV disease in renal transplant recipients. We have retrospectively analyzed CMV disease in 120 renal transplant recipients and recorded the demographic features, clinical manifestations, and immunosuppressive regimens. Twenty-nine recipients (24.1%) developed CMV disease after a median interval of 2.8 +/- 2,6 months from transplantation. CMV disease developed in 36.3% of recipients who received basiliximab as induction therapy and 21.4% of recipients who were treated with anti-thymocyte globulin (ATG). The most commonly used immunosuppressive regimen was cyclosporine-A (CsA)-based (79.3%). The mean cumulative steroid dose until the diagnosis was 3,600 mg methyl prednisolone per patient. Malaise, fever, and diarrhea were the most common symptoms. Gastritis, pneumonia, and transaminitis were the most commonly seen end-organ involvements. Frequent laboratory findings were leukopenia (34.5%), increased serum creatinine level (34.5%), and leukocytosis (20.7%). We performed renal biopsy to seven patients and detected acute rejection in four patients. In 25 patients, immunosuppressive treatment was modified. Relapsing CMV disease was seen in seven patients. In our study, CMV disease was seen in recipients who were treated with basiliximab, a finding similar to recipients who were treated with ATG.


Proximal tubular injury attenuates outer medullary hypoxic damage: studies in perfused rat kidneys.
The straight segment (S3) of the proximal tubule is predominantly damaged during renal ischemia-reflow, whereas medullary thick ascending limbs (mTALs) are principally affected in other models of hypoxic acute tubular necrosis (ATN). Since the latter injury pattern largely depends on the extent of reabsorptive activity during hypoxic stress, we hypothesized that proximal tubular damage might attenuate downstream mTAL injury by means of diminished distal solute delivery for reabsorption. In isolated rat kidneys perfused for 90 min with oxygenated Krebs-Henseleit solution, mTAL necrosis developed in 75 +/- 3% of tubules in the mid-inner stripe of the outer medulla. By contrast, S3 segments in the outer stripe were minimally affected, with tubular fragmentation involving some 5 +/- 2% of tubules. In kidneys subjected in vivo to proximal tubular injury and subsequently used for isolated perfusion studies, the injury pattern was inverted: following 20 and 30 min ischemia and reflow for 24 h, S3 fragmentation rose to 18 +/- 16% and 72 +/- 13%, while mTAL damage was reduced to 33 +/- 10 and 24 +/- 8%, respectively. In kidneys subjected in vivo to D-serine S3 necrosis rose to 100%, while mTAL damage fell to 1 +/- 1% (p < 0.001). Substantial S3 tubular collapse (involving approximately 30% of tubules) and inner stripe interstitial hemorrhage were also noted, exclusively in kidneys subjected to ischemia-reflow. Proximal tubular necrosis alone or in combination with collapse inversely correlated with mTAL necrosis (R = -0.51 and -0.72, respectively, p < 0.003). This cogent inverse association might imply that disruption of the proximal nephron attenuates downstream mTAL necrosis by a reduction of distal tubular reabsorptive workload.


Sex-related differences in spatial ability: more evidence for convergence.
Sex-related differences in spatial ability, favoring males, have frequently been reported in the literature. Recent analyses, however, have found indications of a convergence in the scores of men and women on spatial tests over the years. This research examined the evidence for such a secular trend in a German population using data of 18 samples that had completed the Cube Perspectives Test, a measure of spatial visualization ability. The largest effect size (d = .77) was found for a sample tested in 1978, the smallest difference (d = .38) was observed for a sample tested in 1987. There was a clear trend narrowing the sex-related differences; the correlation between the recency of the data and the respective d-value was -.926. The convergence of the scores of men and women proved to be stronger than in the previous studies.


Comparison of the efficacy and safety profiles of two fixed-dose combinations of antihypertensive agents, amlodipine/benazepril versus valsartan/hydrochlorothiazide, in patients with type 2 diabetes mellitus and hypertension: a 16-week, multicenter, randomized, double-blind, noninferiority study.
Hypertension is a prevalent condition that is closely associated with chronic complications in patients with diabetes. Fixed-dose combination therapy is currently recommended for the treatment of hypertension due to the advantage of reducing the pill burden. However, the effects of combination therapy may be diverse because of the different components. We examined blood pressure reduction and metabolic alterations after amlodipine/benazepril and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus and hypertension and microalbuminuria. This randomized, double-blind, parallel comparison, noninferiority clinical trial included patients with type 2 diabetes mellitus and hypertension and microalbuminuria detected within the past year. After a 2-week, placebo run-in period, patients were assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide for 16 weeks. The primary end point was mean change in diastolic blood pressure. The prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide). If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would be considered noninferior to valsartan/hydrochlorothiazide. Of the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male, mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received at least 1 dose of study medication and were included in the intention-to-treat population. In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic blood pressure (difference, -0.9 mm Hg; 95% CI, -3.5 to 1.6). The mean change in systolic blood pressure was not significantly different (2.4 mm Hg; 95% CI, -1.2 to 6.0) between study groups (P = 0.195) in the per-protocol population. However, data from the intention-to-treat population suggest that patients in the amlodipine/benazepril group may have better metabolic outcomes than those in the valsartan/hydrochlorothiazide group; specifically, a preservation of the estimated glomerular filtration rate (5.7 mL/min/1.73 m(2) [95% CI, 1.9 to 9.6]; P = 0.004) and improvements in glycosylated hemoglobin (-0.5% [95% CI, -0.7 to -0.2]; P < 0.001), fasting triglycerides (-0.4 mmol/L [95% CI, -0.7 to -0.2]; P = 0.002), HDL-C (0.07 mmol/L [95% CI, 0.01 to 0.12]; P = 0.022), and uric acid (-57.5 μmol/L [95% CI, -74.8 to -40.3]; P < 0.001). There were no significant differences in adverse effects between groups, with the exception of more respiratory disorders in the amlodipine/benazepril group than in the valsartan/hydrochlorothiazide group (17 vs 5; P = 0 .006). The study results suggest that amlodipine/benazepril is noninferior to valsartan/hydrochlorothiazide with regard to blood pressure reduction and that this combination exerts beneficial effects on renal function, glucose control, HDL-C, and triglyceride levels compared with valsartan/hydrochlorothiazide. However, respiratory adverse events (particularly coughing) were more frequently reported in the amlodipine/benazepril group. ClinicalTrials.gov identifier: NCT01375322.


Telomere crisis in kidney epithelial cells promotes the acquisition of a microRNA signature retrieved in aggressive renal cell carcinomas.
Telomere shortening is a major source of chromosome instability (CIN) at early stages during carcinogenesis. However, the mechanisms through which telomere-driven CIN (T-CIN) contributes to the acquisition of tumor phenotypes remain uncharacterized. We discovered that human epithelial kidney cells undergoing T-CIN display massive microRNA (miR) expression changes that are not related to local losses or gains. This widespread miR deregulation encompasses a miR-200-dependent epithelial-to-mesenchymal transition (EMT) that confers to immortalized pre-tumoral cells phenotypic traits of metastatic potential. Remarkably, a miR signature of these cells, comprising a downregulation of miRs with conserved expression in kidney, was retrieved in poorly differentiated aggressive renal cell carcinomas. Our results reveal an unanticipated connection between telomere crisis and the activation of the EMT program that occurs at pre-invasive stages of epithelial cancers, through mechanisms that involve miR deregulation. Thus, this study provides a new rational into how telomere instability contributes to the acquisition of the malignant phenotype.


Lack of Brain Insulin Receptor Substrate-1 Causes Growth Retardation, With Decreased Expression of Growth Hormone-Releasing Hormone in the Hypothalamus.
Insulin receptor substrate-1 (Irs1) is one of the major substrates for insulin receptor and insulin-like growth factor-1 (IGF-1) receptor tyrosine kinases. Systemic Irs1-deficient mice show growth retardation, with resistance to insulin and IGF-1, although the underlying mechanisms remain poorly understood. For this study, we generated mice with brain-specific deletion of Irs1 (NIrs1KO mice). The NIrs1KO mice exhibited lower body weights, shorter bodies and bone lengths, and decreased bone density. Moreover, the NIrs1KO mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. Although the ability of the pituitary to secrete growth hormone (GH) remained intact, the amount of hypothalamic growth hormone-releasing hormone (GHRH) was significantly decreased and, accordingly, the pituitary GH mRNA expression levels were impaired in these mice. Plasma GH and IGF-1 levels were also lower in the NIrs1KO mice. The expression levels of GHRH protein in the median eminence, where Irs1 antibody staining is observed, were markedly decreased in the NIrs1KO mice. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured N-38 hypothalamic neurons. In conclusion, brain Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.


RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review.
Gene mutation analysis was performed on a family with familial hemophagocytic lymphohistiocytosis (FHL) so as to provide an accurate etiological diagnosis, leading to genetic counseling for the family members. The clinical data of two probands (siblings) with FHL in one family were analyzed, and eight genes related to the onset of the primary hemophagocytic lymphohistiocytosis (pHLH) (PRF1, UNC13D, STX11, STXBP2, SH2D1A, BIRC4/XIAP, Rab27a, LYST) were detected and analyzed in the probands and their parents with whole exome sequencing. Proband 1 was a two-year-old male with the clinical manifestations of fever, hepatosplenomegaly, and a decreased peripheral blood cell count, sCD25: 12504pg/mL. The results of genetic testing showed that there was a c.1349C>T heterozygous missense mutation and a c.853_855del heterozygous mutation in the PRF1 in proband 1. Proband 2 was an eight-year-old female with the clinical manifestations of convulsions and disturbance of consciousness with fever. The genetic test results were the same as those of proband 1. There was a single heterozygous mutation in the parents of the probands, and both probands had compound heterozygous mutations. According to the clinical manifestations, laboratory tests, and results of the family molecular genetic testing, the probands could be clinically diagnosed as FHL2. The results of gene sequencing revealed that this was an autosomal recessive family with familial hemophagocytic syndrome. A rare pathogenic mutation (c.853_855del) in the PRF1 was discovered in the two patients with HLH.


Transepithelial and intracellular potentials in isolated Malpighian tubules of tenebrionid beetle.
Malpighian tubules of Onymacris plana (Coleoptera: Tenebrionidae) have been isolated for measurement of transepithelial and intracellular potentials, before and during stimulation of fluid secretion. In a bathing medium resembling the hemolymph composition of the insect, the transepithelial potential (VT) was approximately 13 mV, lumen positive. VT was subject to drift and frequently showed super-imposed regular oscillations, which were apparently action potentials associated with contractions of muscle fibers running along the tubules. Although tubules of Onymacris are approximately 8 cm long, the basal membrane potential (Vb) did not vary with distance along the tubule, averaging -31 mV. Addition of adenosine 3',5'-cyclic monophosphate (cAMP) or diuretic hormone (DH) homogenate to the bathing medium had no effect on Vb, but opposing effects on VT: cAMP caused it to increase to 60 mV, whereas DH homogenate caused a rapid drop in VT to almost zero. Ion substitutions in the bathing medium showed that under control conditions beetle tubules possessed appreciable basal permeability to both K and Cl ions, with a 10-fold reduction in bath K concentration hyperpolarizing Vb by 54 mV. The basal K and Cl channels were partially blocked by barium and thiocyanate ions, respectively. Stimulation with cAMP increased the apical membrane potential (Va) and significantly reduced the Cl permeability of the basal membrane, whereas its Na permeability remained negligible.


5-(Furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f), a new synthetic compound, causes human fibrosarcoma HT-1080 cell apoptosis by disrupting tubulin polymerisation and inducing G2/M arrest.
In the current study, we synthesized a series of new compounds targeting tubulin and tested their anti-proliferative activities. Among these new synthetic com-pounds, 5-(furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f) exhibited significant anti-proliferative activity against different human cancer cell lines including human gastric adenocarcinoma SGC-7901, human non-small cell lung cancer A549, and human fibrosarcoma HT-1080. As a result, 6f was selected to further test the sensitivity to different cancer cell lines including human cervical cancer cell line HeLa, human breast cancer cell line MCF-7, non-small cell lung cancer cell line A549, human liver carcinoma cell line HepG-2, human oral squamous cell carcinoma cell lines KB, SGC-7901 and HT-1080. Among these cell lines, HT-1080 and HeLa are the most sensitive. Therefore, HT-1080 was selected to further explore the properties of anti-proliferative activity and the underlying mechanisms. Our data proved that 6f exhibited strong anti-proliferative effects against HT-1080 cells in a time- and dose-dependent manner. We showed that the growth inhibitory effect of 6f in HT-1080 cells was related with microtubule depolymerisation. Molecular docking studies revealed that 6f interacted and bound efficiently with the colchicine-binding site of tubulin. In addition, 6f treatment induced G2/M cell cycle arrest dose-dependently and subsequently induced cell apoptosis. Western blot study indicated that upregulation of cyclin B1 and p-cdc2 was related with G2/M arrest. 6f-induced cell apoptosis was associated with both mitochondrial and death receptor pathway. In conclusion, our data showed that 6f, among the newly synthetic compounds, exhibited highest anti-proliferative activity by disrupting the microtubule polymerisation, causing G2/M arrest and subsequently inducing cell apoptosis in HT-1080 cells. Hence, 6f is a promising microtubule depolymerising agent for the treatment of various cancers especially human fibrosarcoma.


Deconvolution of Mass Spectral Interferences of Chlorinated Alkanes and Their Thermal Degradation Products: Chlorinated Alkenes.
Chlorinated paraffins (CPs) are high production volume chemicals and ubiquitous environmental contaminants. CPs are produced and used as complex mixtures of polychlorinated n-alkanes containing thousands of isomers, leading to demanding analytical challenges. Due to their high degree of chlorination, CPs have highly complex isotopic mass patterns that often overlap, even when applying high resolution mass spectrometry. This is further complicated in the presence of degradation products such as chlorinated alkenes (CP-enes). CP-enes are formed by dehydrochlorination of CPs and are expected thermal degradation products in some applications of CPs, for example, as metal working fluids. A mathematical method is presented that allows deconvolution of the strongly interfered measured isotope clusters into linear combinations of isotope clusters of CPs and CP-enes. The analytical method applied was direct liquid injection into an atmospheric pressure chemical ionization source, followed by quadrupole time-of-flight mass spectrometry (APCI-qTOF-MS), operated in full scan negative ion mode. The mathematical deconvolution method was successfully applied to a thermally aged polychlorinated tridecane formulation (Cl5-Cl9). Deconvolution of mass patterns allowed quantifying fractions of interfering CPs and CP-enes. After exposure to 220 °C for 2, 4, 8, and 24 h, fractions of CP-enes within the respective interfering clusters increased from 0-3% at 0 h up to 37-44% after 24 h. It was shown that thermolysis of CPs follows first-order kinetics. The presented deconvolution method allows CP degradation studies with mass resolution lower than 20000 and is therefore a good alternative when higher resolution is not available.


The effect of protein ingestion on the metabolic response to oral glucose in normal individuals.
Eight normal subjects were given 50 g protein, 50 g glucose, or 50 g protein + 50 g glucose. Plasma glucose, insulin, C-peptide, glucagon, alpha-amino nitrogen (AAN), and nonesterified fatty acid (NEFA) responses were then determined over 4 h. Protein stimulated only a modest insulin rise and the area above fasting baseline was only 28% of that after glucose. The sum of the serum insulin area following protein ingestion and that following glucose ingestion was 100.4% of the combination meal. C-peptide changes confirmed the insulin response. The addition of glucose to the protein meal resulted in a 60 min delay in glucagon and AAN rise compared to the protein meal alone. Subsequently AAN and glucagon increased to levels greater than or equal to those observed after protein ingestion alone. In summary, protein is a much less potent secretagogue for insulin than is glucose in normal individuals, and the effect on insulin secretion is not synergistic. Addition of glucose to a protein meal results in a delayed rise in AAN and glucagon concentrations in normal subjects.


High purity isolation and quantification of semiconducting carbon nanotubes via column chromatography.
The isolation of semiconducting carbon nanotubes (CNTs) to ultrahigh (ppb) purity is a prerequisite for their integration into high-performance electronic devices. Here, a method employing column chromatography is used to isolate semiconducting nanotubes to 99.9% purity. The study finds that by modifying the solution preparation step, both the metallic and semiconducting fraction are resolved and elute using a single surfactant system, allowing for multiple iterations. Iterative processing enables a far more rapid path to achieving the level of purities needed for high performance computing. After a single iteration, the metallic peak in the absorption spectra is completely attenuated. Although absorption spectroscopy is typically used to characterize CNT purity, it is found to be insufficient in quantifying solutions of high purity (>98 to 99%) due to low signal-to-noise in the metallic region of ultrahigh purity solutions. Therefore, a high throughput electrical testing method was developed to quantify the degree of separation by characterizing ∼4000 field-effect transistors fabricated from the separated nanotubes after multiple iterations of the process. The separation and characterization methods described here provide a path to produce the ultrahigh purity semiconducting CNT solutions needed for high performance electronics.


Interpreting the judgment of surgical faculty regarding resident competence.
It is reasonable to propose that competence is a multifaceted characteristic defined in part by some minimum level of knowledge and skill. In this study we examined the relationship between surgical faculty's judgment of clinical competence, as measured by a surgical resident objective structured clinical examination (OSCE), and the residents' objective performance on the skills being tested. Fifty-six general surgery residents at all levels of training participated in a 30-station OSCE. At the completion of each station, the faculty proctor made several overall judgments regarding each resident's performance, including a global judgment of competent or not competent. The competence judgment was applied to the objective percentage performance score in three different ways to construct methods for determining competence based solely upon this objective percentage score. The average mean competent score (MCS) across the stations was 61%, and the average mean noncompetent score (MNCS) was 38%. The difference between MCS and MNCS for each station was very consistent. Upper threshold scores above which a judgment of competent was always made, and lower threshold scores below which a judgment of noncompetent was always made were observed. Overall, the average mean and threshold scores for competent and noncompetent groups were remarkably similar. For performance scores in the range between the threshold competent and noncompetent scores at each station, measures other than objective performance on the skills being evaluated determined the judgment of competent or not competent. Empirically determined minimum acceptable standards for objective performance in clinical skills and knowledge appeared to have been subconsciously applied to the competence judgment by the faculty evaluators in this study. Other factors appeared to have become determinate when the objective performance score fell within a range of uncertainty.


The ocular distribution of methazolamide after corneal and scleral administration: the effect of ionization state.
The accession of methazolamide in ionized and unionized form to cornea, sclera, aqueous humor and ciliary process was studied 10 minutes following separate application to either sclera or cornea of a 1 mM solution. Cornea and ciliary process concentrations were 27.3 and 14.5 microM for unionized application to cornea and 10.1 and 7.1 microM for ionized application. Bulk aqueous humor concentrations were much lower, 3.1 and 1.1 microM, and cannot account for drug found in ciliary process on this time scale. Scleral application of drug, by contrast, gave undetectable ciliary process concentrations. These results are presented as a model for drug disposition following single drop topical sulfonamide therapy. The scleral pathway for drug delivery to ciliary process was further tested by application to sclera of 300 microL of either a 1 mM ionized or unionized solution for 30 minutes or as a 2% (85.5 mM) ionized solution for 30 minutes. In these series, red cell carbonic anhydrase was presaturated at -24 hours with drug to remove a possible route for loss of drug from sclera, that of the systemic circulation and the high concentration of carbonic anhydrase in red cells. After either ionized or unionized application, approximately 1 microM was detected in ciliary process, but all drug was attributable to the blood content of the tissue and the drug bound to red cell carbonic anhydrase. After 2% dosing, 4 microM was detected in ciliary process after allowance for drug in red cells. This concentration is below that necessary for inhibition of ciliary process carbonic anhydrase, suggesting that especially with regard to topical sulfonamide therapy, the corneal route of drug delivery to ciliary process predominates greatly over the scleral route.


Age-dependent increases of calcium and phosphorus in human epiglottal cartilage.
To elucidate compositional changes of the elastic cartilage with aging, the authors investigated age-related changes of elements in the epiglottal cartilages by inductively coupled plasma-atomic emission spectrometry. After the ordinary dissection by medical students at Chiang Mai University was finished, the epiglottises were resected from the subjects. The epiglottal cartilages were isolated and the element contents were determined. The subjects consisted of 11 men and 14 women, ranging in age from 39 to 92 yr old. It was found that although the extent of accumulation of calcium and phosphorus was slight, calcium and phosphorus increased progressively in the epiglottal cartilages with aging. In contrast, sulfur, magnesium, zinc, iron, and sodium did not change significantly in them. Regarding the relationships among elements, it was found that there were significant correlations among calcium, phosphorus, magnesium, and sodium in the epiglottal cartilages, with one exception between calcium and sodium contents. In comparison between men and women, no significant differences were found in the predominant elements such as calcium, sulfur, and phosphorus in the epiglottal cartilages.


[Fragments of the history of healthcare for users of alcohol and other drugs in Brazil: from Justice to Public Health].
The purpose of this article is to identify, factors that could be associated to the establishment of the country's health policy for users of alcohol and other drugs in 2003. It makes particular use of semi-structured interviews, as well as a study of the literature and documents. The article shows that the Brazilian State's approach to alcohol and drugs emerged in the early 20th century with the creation of a legal and institutional apparatus designed to control the sale and use of drugs, justified by the need to assure public security and public health. This apparatus permitted the development of healthcare practices for drug users based on the penalties it proposed. The article concludes that even though the rationales behind legal and public health measures do not always coincide, some of the practices that emerged in the legal sphere did help provide the conditions needed for the creation of a health policy for alcohol and drug users in Brazil in 2003.


The inner city and drug use: initial findings from an epidemiological study.
Although scientific and policy statements regarding drugs often suggest that there are grave problems of drug use within America's inner cities, the evidence that supports these statements is often based on anecdotal or incomplete data. This study of African-American adults from the Woodlawn study followed longitudinally partially fills that gap, at least for learning more about those who spend some or all of their childhood within an inner city neighborhood. We found few differences between the lifetime prevalence of drug use and a national representative sample of adults of the same age range. Furthermore, a national household survey of African-Americans of similar age living in six central cities also reported low lifetime rates of illicit drug use. Nevertheless, those from the Woodlawn cohort had higher rates of use of illicit drugs in the past year than the national sample, especially those still living in areas with high rates of poverty. Additionally, reports of heavy drug trafficking were much greater in the inner city areas than in the suburbs.


Successful treatment of Pseudomonas cepacia endocarditis with trimethoprim-sulfamethoxazole.
A patient with a history of alcoholism and drug abuse who developed Pseudomonas cepacia endocarditis is described. The organism was found to be resistant in vitro to all common antimicrobial agents except chloramphenicol and trimethoprim-sulfamethoxazole. Treatment failed with penicillin and streptomycin and later with chloramphenicol. Orally administered trimethoprim-sulfamethoxazole, however, resulted in sterilization of the patient's blood and aortic valve which was resected 27 days after the start of therapy. A 6-week course of therapy was completed and, to date (6 months after treatment), there has been no recurrence.


Chicken sine oculis binding protein homolog (sobp), a novel gene that may regulate feather development.
Feathers are appendages of skin in avians and provide a model for analyzing skin appendage morphogenesis. The feathers of Chinese Silky (CS) and White Leghorn (WL) chickens have distinct phenotypes. Based on preliminary genetic results, we cloned the chicken gene sobp (encoding sine oculis binding protein homolog, which is expressed at a higher level in the dorsal skin and in the feather follicle in the WL compared with the CS. The reverse-transcription PCR and quantitative real-time PCR indicated that sobp was expressed in many tissues and was continuously expressed during embryonic development in both strains. Northern and Western blotting indicated that the mRNA of sobp was approximately 5 kb and the SOBP protein was approximately 96 kDa. The expressions of signaling molecules that affect feather development were similar. This study is the first report of sobp expression in chickens. Our results suggest that sobp might regulate distinct feather type.


Host selection and feeding preference of Agrilus planipennis (Coleoptera: Buprestidae) on ash (Fraxinus spp.).
We studied the host selection behavior and feeding preference of the emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae). A. planipennis is an exotic forest insect pest native to Asia that was discovered in North America in 2002 and is causing widespread mortality of ash trees (Fraxinus spp.) in southeast Michigan and surrounding states. We compared host selection and feeding behavior on different species of ash including Manchurian ash (F. mandshurica Rupr.), green ash (F. pennsylvanica Marsh), white ash (F. americana L.), black ash (F. nigra Marsh), blue ash (F. quadrangulata Michx.), and European ash (F. excelsior L). Manchurian ash is native to Asia, whereas the other species (native to North America or Europe) represent novel hosts for A. planipennis. Beetles distributed themselves more frequently and fed to a greater extent on green, black, and white ash compared with blue, European, and Manchurian ash. Although beetles consumed every ash species offered to them, Manchurian ash and blue ash were least preferred in feeding bioassays. When we analyzed the volatile content of intact and girdled ash for quantitative variation in 11 compounds that elicited antennal activity, we found that the overall volatile profiles of the six ash species differed significantly in their relative amounts of antennally active compounds. Green ash has lower relative amounts of volatiles compared with Manchurian ash, which might render it more attractive and less resistant to A. planipennis. Lower tolerance and resistance of green ash might make it more susceptible to mortality compared with Manchurian ash, which coevolved with the beetle in its native range. Repellent odors, potential antifeedants, and genes for resistance in Manchurian ash could be explored for methods to manage A. planipennis populations.


Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.
In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.


Terpenoid-based defenses in conifers: cDNA cloning, characterization, and functional expression of wound-inducible (E)-alpha-bisabolene synthase from grand fir (Abies grandis).
(E)-alpha-Bisabolene synthase is one of two wound-inducible sesquiterpene synthases of grand fir (Abies grandis), and the olefin product of this cyclization reaction is considered to be the precursor in Abies species of todomatuic acid, juvabione, and related insect juvenile hormone mimics. A cDNA encoding (E)-alpha-bisabolene synthase was isolated from a wound-induced grand fir stem library by a PCR-based strategy and was functionally expressed in Escherichia coli and shown to produce (E)-alpha-bisabolene as the sole product from farnesyl diphosphate. The expressed synthase has a deduced size of 93.8 kDa and a pI of 5. 03, exhibits other properties typical of sesquiterpene synthases, and resembles in sequence other terpenoid synthases with the exception of a large amino-terminal insertion corresponding to Pro81-Val296. Biosynthetically prepared (E)-alpha-[3H]bisabolene was converted to todomatuic acid in induced grand fir cells, and the time course of appearance of bisabolene synthase mRNA was shown by Northern hybridization to lag behind that of mRNAs responsible for production of induced oleoresin monoterpenes. These results suggest that induced (E)-alpha-bisabolene biosynthesis constitutes part of a defense response targeted to insect herbivores, and possibly fungal pathogens, that is distinct from induced oleoresin monoterpene production.


A histochemical study on the effects of photoperiod on gonadal and adrenal function in the male bank vole (Clethrionomys glareolus).
NADH- and NADPH-diaphorases, 3alpha-, delta5-3beta-, 11beta- and 17beta-hydroxy-steroid dehydrogenases (HSD) and lipids were studied histochemically in the testes and adrenals of male bank voles kept in a long (16L:8D) or a short (8L:16D) photoperiod (Groups L and S, respectively). At 67 days of age the Group L males were heavier and had active and significantly larger testes than Group S males. The testes of Group S males were regressed and were also significantly smaller than those of 18-day-old animals born and reared in a 18L:6D photoperiod. Lipid droplets were detected in the Leydig cells and intratubular spaces in the testes of Group L animals, but were absent from those of Group S voles. The adrenal cortex of the Group L animals was virtually devoid of lipids, but large lipid inclusions were present in the basal zona fasciculata of the Group S voles. In the Group L testes the diaphorase activities were more intense and the difference in enzymic activity between the seminiferous epithelium and the Leydig cells was more pronounced (especially for NADH-diaphorase) than that in the testes of Group S animals. Moreover, the 3alpha-- and delta5-3beta-HSD activities were much stronger in the testes of sexually active animals; 17beta-HSD activity was present in the Leydig cells of the active testes, and absent in the regressed testes. There was no marked difference between the two groups of animals with regard to the distribution or intensity of diaphorases, 3alpha-, delta5-3beta-, 11beta- or 17beta-HSD in the adrenal cortex. It is concluded that a decline in steroid synthesis occurs in the testes of voles kept in a short photoperiod. The large lipid inclusions observed in the adrenal cortex of such animals suggest decreased corticosteroid synthesis and/or secretion.


English National Health Service's savings plan may have helped reduce the use of three 'low-value' procedures.
The pressure to contain health expenditures is unprecedented. In England a flattening of the health budget but increasing demand led the National Health Service (NHS) to seek reductions in health expenditures of 17 percent over four years. The spending cuts were to be achieved through improvements in service quality and efficiency, including reducing the use of ineffective, overused, or inappropriate procedures. However, the NHS left it to the local commissioning (or funding) organizations, known as primary care trusts, to determine what steps to take to reduce spending. To assess whether the initiative had an impact, we examined six low-value procedures: spinal surgery for lower back pain, myringotomy to relieve eardrum pressure, inguinal hernia repair, cataract removal, primary hip replacement, and hysterectomy for heavy menstrual bleeding. We found significant reductions in three of the six procedures-cataract removal, hysterectomy, and myringotomy-in the program's first year, compared to prior years' trends. However, changes in the rates of all examined procedures varied widely across commissioning organizations. Our findings highlight some of the challenges of making major budget cuts in health care. Reducing ineffective spending remains a significant opportunity for the US health care system, and the English experience may hold valuable lessons.


Implementation of TMA and digitalization in routine diagnostics of breast pathology.
To ensure optimal treatment of breast cancer patients, breast tumours are classified based on clinico-pathological features. As part of this process, routine diagnostics of breast tumours includes histological typing and grading, as well as profiling by use of an immunohistochemistry panel of antibodies, probes and in situ hybridization. This will, as a minimum, include assessment of oestrogen receptor (OR) and HER2. The individual preparation and staining of many breast tumours in a large laboratory with this standard panel is thus time consuming and costly. Herein, we show that in breast cancer routine diagnostics the use of the tissue microarray technique in combination with digitalization of the stained multi-slides is not only economical, with a considerable cost reduction, but it also enhances standardization of tumour profiling. We demonstrate that 2 mm breast tumour cores correlate with the corresponding tumour on whole mount slides, regarding staining/hybridizing results with the biomarkers in our panel consisting of human epidermal growth factor receptor 2, OR and Topiomerase IIa. Furthermore, we show that simultaneous staining/hybridizing of multiple breast tumour specimens reduces variation of staining/hybridizing quality, hereby increasing reliability of interpretation. By scanning and digitalization of the stained and hybridized multi-slides, we could optimize documentation and filing of the results. Our work is an example of translational research by implementing a tool in daily diagnostics originally developed for high throughput analyses in the search for prognostic and predictive markers in targeted medicine.


HMM-FRAME: accurate protein domain classification for metagenomic sequences containing frameshift errors.
Protein domain classification is an important step in metagenomic annotation. The state-of-the-art method for protein domain classification is profile HMM-based alignment. However, the relatively high rates of insertions and deletions in homopolymer regions of pyrosequencing reads create frameshifts, causing conventional profile HMM alignment tools to generate alignments with marginal scores. This makes error-containing gene fragments unclassifiable with conventional tools. Thus, there is a need for an accurate domain classification tool that can detect and correct sequencing errors. We introduce HMM-FRAME, a protein domain classification tool based on an augmented Viterbi algorithm that can incorporate error models from different sequencing platforms. HMM-FRAME corrects sequencing errors and classifies putative gene fragments into domain families. It achieved high error detection sensitivity and specificity in a data set with annotated errors. We applied HMM-FRAME in Targeted Metagenomics and a published metagenomic data set. The results showed that our tool can correct frameshifts in error-containing sequences, generate much longer alignments with significantly smaller E-values, and classify more sequences into their native families. HMM-FRAME provides a complementary protein domain classification tool to conventional profile HMM-based methods for data sets containing frameshifts. Its current implementation is best used for small-scale metagenomic data sets. The source code of HMM-FRAME can be downloaded at http://www.cse.msu.edu/~zhangy72/hmmframe/ and at https://sourceforge.net/projects/hmm-frame/.


[Diagnosis of overweight and obesity in schoolchildren: utilization of the body mass index international standard].
To evaluate the agreement between the body mass index international standard and body fat for the diagnosis of overweight and obesity in schoolchildren. 528 schoolchildren between 6 and 10 years of age, of both sexes, had their weight and height measured. They were then classified as normal, underweight, overweight or obese using the body fat index for age. Body fat was estimated based on the sum of triceps and subscapular, triceps and calf skinfold measurements and waist and hip circumference. Overweight and obesity were found in 21.2% of the girls and 18.8% of the boys. The average percentage of body fat in the normal children (17.7%) was statistically different from that of overweight (27%) and obese (29.4%) children (p < 0.02). The average waist and hip circumference also differed significantly between normal boys and girls (56.9 cm and 67.7 cm) and overweight children (65.9 cm and 77 cm) (p < 0.01). There was no significant difference between groups in terms of average waist to hip ratio. The percentage of body fat, waist and hip circumference were significantly correlated with body mass index (p < 0.01). Body mass index for age was an adequate indicator of overweight and obesity in group studied, with a good agreement with body fat.


Gastrointestinal non colorectal cancer. Do elderly patients need a specific management?
Elderly patients (65 years and over) develop often, sometimes predominantly , esophageal, gastro esophageal junction, gastric and pancreatic cancer (gastrointestinal non colorectal cancer). Most clinical trials exclude elderly patients from accrual considering aging a potential risk factor. In fact an elderly patient can develop greater toxicity than a younger patient from oncologic treatments (chemotherapy, radiotherapy, target therapies) due to a worse function of vital organs. We analyzed the current scientific literature, searching articles since 1990, about gastrointestinal non colorectal cancer in elderly patients, to establish if they need a specific management, different from younger patients. Data from analyzed studies, both gastro esophageal and pancreatic cancer, are contradictory. In some reports elderly patients don't seem to bring greater toxicity than younger. Other trials consider that dose-adjustment to renal function is need in elderly patients, but these trials are very few. Other trials may include several biases such as accrual of "only fit" elderly patients. It is very important in elderly patients with higher risk of toxicity, to distinguish the aim of cancer treatment: is it curative or palliative? Furthermore, in this type of patients the most important target is probably maintaining the quality of life especially in gastric and pancreatic cancer that often started as advanced disease. For these valuation chronological age alone is not sufficient. Another very important factor in elderly cancer patients is the geriatric assessment including not only age but also functional, social and mental status.


Explaining tolerance for bitterness in chocolate ice cream using solid chocolate preferences.
Chocolate ice cream is commonly formulated with higher sugar levels than nonchocolate flavors to compensate for the inherent bitterness of cocoa. Bitterness, however, is an integral part of the complex flavor of chocolate. In light of the global obesity epidemic, many consumers and health professionals are concerned about the levels of added sugars in foods. Once a strategy for balancing undesirable bitterness and health concerns regarding added sugars has been developed, the task becomes determining whether that product will be acceptable to the consumer. Thus, the purpose of this research was to manipulate the bitterness of chocolate ice cream to examine how this influences consumer preferences. The main goal of this study was to estimate group rejection thresholds for bitterness in chocolate ice cream, and to see if solid chocolate preferences (dark vs. milk) generalized to ice cream. A food-safe bitter ingredient, sucrose octaacetate, was added to chocolate ice cream to alter bitterness without disturbing other the sensory qualities of the ice cream samples, including texture. Untrained chocolate ice cream consumers participated in a large-scale sensory test by indicating their preferences for blinded pairs of unspiked and spiked samples, where the spiked sample had increasing levels of the added bitterant. As anticipated, the group containing individuals who prefer milk chocolate had a much lower tolerance for bitterness in their chocolate ice cream compared with the group of individuals who prefer dark chocolate; indeed, the dark chocolate group tolerated almost twice as much added bitterant in the ice cream before indicating a significant preference for the unspiked (control) ice cream. This work demonstrates the successful application of the rejection threshold method to a complex dairy food. Estimating rejection thresholds could prove to be an effective tool for determining acceptable formulations or quality limits when considering attributes that become objectionable at high intensities.


Antibodies: an alternative for antibiotics?
In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases.


A polymer-type water-soluble peptidoglycan exhibited both Toll-like receptor 2- and NOD2-agonistic activities, resulting in synergistic activation of human monocytic cells.
Bacterial peptidoglycan (PGN) has been reported to be sensed by cell-surface Toll-like receptor (TLR)2. On the other hand, intracellular NOD-like receptors recognize PGN partial structures: NOD1 and NOD2 recognize the peptide moiety containing diaminopimelic acid, and the muramyldipeptide (MDP) moiety, respectively. In this study, we examined in human monocytic THP-1 cells the pro-inflammatory cytokine-inducing abilities of PGNs and their fragments enzymatically prepared from Staphylococcus epidermidis ATCC 155: a polymer-type water-soluble PGN possessing an intact glycan chain (SEPS) and a monomer-type PGN (SEPS-M). The water-soluble PGN polymer, SEPS, exhibited considerably stronger activities to induce pro-inflammatory cytokines than parent PGNs and the PGN monomer, SEPS-M. Short interference RNA targeting TLR2 and NOD2 markedly reduced the activities of SEPS. In the same experiments, the activities of PGNs were mainly reduced in TLR2-silenced cells, whereas the activities of SEPS-M as well as a synthetic MDP were markedly reduced in NOD2-silenced cells. Furthermore, the PGNs and a reference PGN from Staphylococcus aureus in combination with MDP synergistically induced interleukin-8 in THP-1 cells. These findings strongly suggested that a polymer-type water-soluble PGN fragment, SEPS, exhibits both TLR2-and NOD2-agonistic activities, which induced the synergistic activation of human monocytic cells.


Functional and structural properties of lipid-associated apolipoprotein J (clusterin).
Apolipoprotein J (apoJ, clusterin) is a multifunctional protein normally associated with lipids in plasma and cerebrospinal fluid, and secreted as lipoparticles by hepatocytes and astrocytes. To investigate whether the structural and functional properties of apoJ are modulated upon binding to lipids, we prepared apoJ high-density lipoprotein (HDL)-like particles employing either synthetic or plasma HDL-derived lipids. The majority of the resulting lipoparticles contained one molecule of apoJ per particle and exhibited the same alpha2 electrophoretic mobility characteristic of apoJ-containing plasma HDL. Particle size seemed to be dependent on the presence of cholesterol in the lipid mixture and ranged from diameters of 10 nm in the presence of cholesterol to 20 nm in the absence of cholesterol. CD analysis and Fourier-transform infrared spectroscopy revealed similar changes in the apoJ secondary structure induced by its incorporation into lipoparticles, namely a decrease in alpha-helix content and an increase in beta-turn structures. Two functional assays, the binding interaction with Alzheimer's amyloid beta peptides and the inhibitory activity of the complement membrane-attack complex, did not detect any changes in apoJ activity following its lipidation (P>0.05). On the contrary, the binding affinity to the cellular receptor megalin was enhanced significantly (P<0.01) after the association with lipids; the K(d) value decreased from 78.8+/-10.7 nM for the delipidated form to 37. 0+/-7.3 nM for apoJ-HDL. Although it is not known whether the structural changes observed are directly responsible for the higher receptor-binding affinity, the data suggest that the complement inhibition and amyloid beta-binding motifs are located in areas of the molecule different from those involved in the apoJ-megalin interaction.


Lactobacillus paracasei AH2 isolated from Chinese sourdough alleviated gluten-induced food allergy through modulating gut microbiota and promoting short-chain fatty acid accumulation in a BALB/c mouse model.
A large number of people worldwide suffer from gluten-induced food allergy. As investigated in our previous research, Lactobacillus paracasei AH2 isolated from traditionally homemade sourdough in Anhui province of China showed the potential to reduce the immune reactivity of wheat protein by in vitro evaluation. However, whether L. paracasei AH2 has a role in alleviating wheat allergy in an in vivo model and its underlying mechanisms have not been elucidated. In this study, the alleviative effects of L. paracasei AH2 on gluten-induced allergic response were evaluated. Compared with a gluten-allergic mouse, L. paracasei AH2 suppressed anaphylaxis symptoms, gluten-specific immunoglobulin E, histamine and interleukin-4. Moreover, L. paracasei AH2 attenuated splenomegaly and induced Th1 or Treg cell differentiation to modulate the Th1/Th2 immune balance toward Th1 polarization. Short-chain fatty acid (SCFA) levels were enhanced after L. paracasei AH2 supplementation, contributing to allergy relief as well as reducing the pH of colonic contents. The α and β diversities of the gut microbiota were modulated by L. paracasei AH2 with increased relative abundance of Lacticaseibacillus and SCFA producers (Faecalibaculum, Alloprevotella and Bacteroides genera), as well as decreased unfavorable Lachnospiraceae_NK4A136_group and Alistipes. Additionally, L. paracasei AH2 protected the intestinal barrier function by upregulating tight junctions and improved the antioxidant activities in serum. Our findings indicate that L. paracasei AH2 could act as a potential probiotic for relieving wheat allergy by modulating the gut microbiota and elevating SCFA levels. © 2023 Society of Chemical Industry.


Hypertension and color blindness in young men.
Medical data from Selective Service registrants born from 1939 to 1941 were studied in Oregon and Colorado. Among 29,119 registrants with medical information (41.3% of all registrants), 1,073 (3.6%) had definite hypertension, and 1,226 (4.2%) had some type of color blindness. In both states, there was a highly significant association between the prevalence of hypertension and the prevalence of color blindness. Thus, definite hypertension was present in 6.0% of color clind individuals but in only 3.6% of those with unimparied color vision, while color blindness occurred in 6.8% with definite hypertension, in 5.8% with borderline hypertension, and in only 4.0% with normal blood pressure. The data did not differentiate among types of color blindness, and the reason for the association is not yet evident.


Epidural nalbuphine versus dexmedetomidine as adjuvants to bupivacaine in lower limb orthopedic surgeries for postoperative analgesia: a randomized controlled trial.
Administration of adjuvant drugs epidurally in combination with local anesthetics offers new dimensions in the management of postoperative pain. This study aimed to compare the addition of either nalbuphine or dexmedetomidine to epidural bupivacaine for postoperative analgesia in lower limb orthopedic surgeries under combined spinal-epidural anesthesia. This prospective randomized double-blind study included 69 patients scheduled for lower limb orthopedic surgeries. Anesthesia was started with 15 mg hyperbaric bupivacaine 0.5% intrathecally, and then an epidural bolus dose of 12 ml (10 ml 0.25% bupivacaine with 2 ml normal saline in group C, 2 ml (10 mg) nalbuphine in group N or dexmedetomidine 2 ml (100 µg) in group D was administered when sensory regression to T10. Postoperatively, when visual analogue scale (VAS) was ≥ 3, an epidural top-up dose of 8 ml (6 ml 0.25% bupivacaine plus 2 ml normal saline in group C, 2 ml (2 mg) nalbuphine in group N or 20 µg dexmedetomidine (2 ml) in group D was given. The primary outcome was to evaluate the duration of postoperative analgesia and secondary outcomes were any side effects and patient satisfaction. The onset of epidural analgesia was 17.83 ± 2.53 versus 13.39 ± 1.27 versus 12.17 ± 1.27 min in groups C, N and D, respectively (p value < 0.001). The mean duration of analgesia was 241.3 ± 14.24 versus 318.38 ± 22.54 versus 365.87 ± 18.01 min in groups C, N and D, respectively (p value < 0.001). The mean sedation score was less in group C than group N and D (P < 0.001). The patient satisfaction score showed the lowest degree of satisfaction in group C (p value < 0.001). Top-up doses consumed and total analgesic requirements were lower in groups N and D than in group C. There was a statistically significant difference between the studied groups regarding VAS over time (p value < 0.001), intraoperative bradycardia (p value 0.029), and shivering (p value 0.029). The addition of either nalbuphine or dexmedetomidine to epidural bupivacaine was effective for postoperative analgesia in terms of onset, duration, and patient satisfaction with the superiority of dexmedetomidine over nalbuphine. Approval from the research ethics committee of the Faculty of Medicine, Zagazig University was obtained with the reference number (ZU-IRB#:7045-15-8-2021) and it was registered under clinicaltrials.gov (NCT05041270) on registration date 13/09/2021.


The invisible reality of arthritis: a qualitative analysis of an online message board.
Living with a chronic illness, such as arthritis, creates many psychosocial stressors, which can be difficult to cope with. Exploring the interactions which take place on an online message board for people with arthritis may provide insight into both the social support offered, as well as highlighting the groups' needs that perhaps are not being met in a more formal 'offline' setting. The aim of this study was to investigate how and why an arthritis online message board was used. A retrospective three-month period of discussions posted on an online message board for people who have arthritis was downloaded into a word document. Collecting data in this manner ensured that completed discussions were captured. Eighty-seven initial messages and 981 replies were analysed. The discussions were analysed using interpretive phenomenological analysis. Four master themes were identified. Firstly, the invisible reality of the condition; secondly, information exchange, whereby users of the message board were shown to be both seeking and providing information; thirdly, while users praised the support they received from family and friends, the support offered and received online was considered to provide additional benefits. Finally, the message board allowed users to share (primarily negative) emotions which they felt unable to express in their offline worlds. Patients do not always understand the information being offered by health care professionals, and they do not have the confidence to ask for clarification. Health care professionals need to ensure that they find a way of checking levels of patient understanding. Failure to do so means that patients may turn to alternative sources, which may not provide accurate information. The study also showed that people with arthritic conditions find it difficult to express how they are feeling in their offline world; furthermore, they find it difficult to ask for support from their significant others, preferring instead to 'suffer in silence' and seek support from the online community, potentially further isolating them from the support of those in their offline world. There is scope for such patients to be both empowered and educated, so that they are better able to ask for the help they need, which in turn will help to counteract the danger of isolation.


The pathogenesis of CIDP: rationale for treatment with immunomodulatory agents.
Current knowledge about the pathogenic mechanisms involved in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) supports an autoimmune etiology. Some of the cell and humorally mediated immune responses that contribute to the development of CIDP resemble those implicated in multiple sclerosis (MS). The effector role of circulating antibodies has recently been revisited. In addition, similar to the situation in MS, histopathologic studies support the heterogeneity of disease mechanisms in CIDP, with variants showing axon damage. In addition to intravenous immunoglobulin (IVIg), prednisone, and plasma exchange, immunomodulatory drugs also were used to treat CIDP, although no definitive trial data are available. One class of immunomodulators, interferon beta formulations, has proven efficacy in the treatment of MS, and because of clinical similarities between the two diseases it is attractive to investigate whether some agents that are effective in the treatment of MS would also be effective in CIDP. Preliminary studies have evaluated the effects of interferon beta formulations in the treatment of CIDP, one of which has shown promising results and warrants further investigation.


1,4,7,10-tetraazacyclododecane metal complexes as potent promoters of phosphodiester hydrolysis under physiological conditions.
Previously reported mono- and dinuclear Zn(II), Cu(II), and Ni(II) complexes of 1,4,7,10-tetrazacyclododecane ([12]aneN4 or cyclen) with different heterocyclic spacers (triazine, pyridine) of various lengths (bi- and tripyridine) or an azacrown-pendant have been tested for the hydrolysis of bis(4-nitrophenyl)phosphate (BNPP) under physiological conditions (pH 7-9, 25 degrees C). All Zn(II) complexes promote the hydrolysis of BNPP under physiological conditions, while those of Cu(II) and Ni(II) do not have a significant effect on the hydrolysis reaction. The hydrolysis kinetics in buffered solutions (0.05 M Bis/Tris, TRIS, HEPES, or CHES, I=0.1 M, NaCl) at 25 degrees C were determined by the initial slope method (product conversion<5%). Comparison of the second-order pH-independent rate constants (kBNPP, M(-1) s(-1)) for the mononuclear complexes ZnL1, ZnL3, and ZnL6, which are 6.1x10 (-5), 5.1x10(-5), and 5.7x10(-5), respectively, indicate that the heterocyclic moiety improves the rate of hydrolysis up to six times over the parent Zn([12]aneN4) complex (kBNPP=1.1x10(-5) M(-1) s(-1)). The reactive species is the Zn(II)-OH- complex, in which the Zn(II)-bound OH- acts as a nucleophile. For dinuclear complexes Zn2L2, Zn2L4, and Zn2L5, the rate of reaction is defined by the degree of cooperation between the metal centers, which is determined by the spacer length. Zn2L2 and Zn2L4 possessing shorter spacers are able to hydrolyze BNPP 1 to 2 orders of magnitudes faster than Zn2L5. The second-order rate constants k of Zn2L4 and Zn2L2 at pH 7, 8, and 9 are significantly higher than those of previously reported related complexes. The high BNPP hydrolytic activity may be related to pi-stacking and hydrophobic interactions between the aromatic spacer moieties and the substrate. Complexes Zn2L4 and Zn2L2 show hydrolytic activity at pH 7 and 8, which allows for the hydrolysis of activated phosphate esters under physiological conditions.


Online practice guidelines: issues, obstacles, and future prospects.
The "guidelines movement" was formed to reduce variability in practice, control costs, and improve patient care outcomes. Yet the overall impact on practice and outcomes has been disappointing. Evidence demonstrates that the most effective method of stimulating awareness of and compliance with best practices is computer-generated reminders provided at the point of care. This paper reviews five steps along the path from the development of a guideline to its integration into practice and the subsequent evaluation of its impact on practice and outcomes. Issues arising at each step and obstacles to moving from one step to the next are described. Last, developments that could help overcome the obstacles are highlighted. These include 1) more rapid knowledge acquisition using data mining, 2) better accommodation to imprecise knowledge in clinical algorithms using fuzzy logic, 3) development of a shareable model for guideline representation and execution, and 4) more widespread availability of clinically robust information systems that support decision-making at the point of care.


Density Functional Theory for Electron Gas and for Jellium.
Density functional theory relies on universal functionals characteristic of a given system. Those functionals in general are different for electron gas and for jellium (electron gas with a uniform background). However, jellium is frequently used to construct approximate functionals for an electron gas (e.g., local density approximation and gradient expansions). The precise relationship of the exact functionals for the two systems is addressed here. In particular, it is shown that the exchange-correlation functionals for the inhomogeneous electron gas and inhomogeneous jellium are the same. This justifies theoretical and quantum Monte Carlo simulation studies of jellium to guide the construction of functionals for an electron gas. Related issues of the thermodynamic limit are noted as well.


Isolation and amino acid composition of sauvagine. An active polypeptide from methanol extracts of the skin of the South American frog Phyllomedusa sauvagei.
The skin of the South American frog Phyllomedusa sauvagei contains a new active polypeptide, sauvagine, which does not belong to any of the peptide families hitherto described in the amphibian skin. The purification procedure involved several successive steps: dialysis, precipitation with ethanol and acetone, gel filtration and ion exchange chromatography. Two forms of sauvagine were separated. The major component (sauvagine I) was submitted to acid hydrolysis. The sauvagine molecule appeared to possess clear hydrophobic characteristics and to consist of a straight chain of 40 amino acid residues, among which the glutamyl-, aspartyl- leucyl- and isoleucyl-residues were particularly well represented. The elucidation of the amino acid sequence in the sauvagine molecule is in progress.


Autofluorescent micelles self-assembled from an AIE-active luminogen containing an intrinsic unconventional fluorophore.
Autofluorescent micelles were constructed via the self-assembly of amphiphilic molecules containing an intrinsic fluorophore. The amphiphilic molecule was an AIE-active luminogen without a conventional π-π conjugated structure. In this unconventional luminogenic system, the hydrogen-bonded amide groups were assigned as the emitting sources.


Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development.
The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite's hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host-parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies.


Thyroid Carcinoma Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography Among Individuals Without Prior Evidence of Thyroid Disease: Relevance and Clinicopathologic Features.
The expanding use of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has contributed to an increasing number of thyroid incidentalomas. The present study aimed to estimate the prevalence of 18F-FDG-PET thyroid incidentalomas and evaluate the clinicopathologic features of thyroid malignancies detected by 18F-FDG-PET. We reviewed all 18F-FDG-PET exams performed at the Portuguese Institute of Oncology, Lisbon, between 2007 and 2012 (n = 9,374). The inclusion criteria were focal thyroid uptake and absence of known thyroid disease. Focal thyroid uptake was observed in 60 out of 9,374 18F-FDG-PET exams (prevalence of 0.64%). Fine-needle aspiration cytology (FNAC) was performed in 23 patients and reported as malignant in 14 cases (56.5% primary thyroid carcinoma; 4.3% secondary malignancy), as benign in 7 cases (30.5%) and as follicular lesion of undetermined significance in 2 cases (8.7%). Fourteen patients had surgery. A final histologic diagnosis of papillary thyroid carcinoma was established in 12 cases (52.2%). Three were multifocal (25.0%); 8 had extrathyroidal extension (66.7%); 5 had angioinvasion (41.7%); 3 had lymph nodes metastases (25.0%) and 2 showed lung metastases (16.7%). Overall, 91.7% were classified as intermediate or high risk. All patients had radioiodine therapy. At the last observation (mean follow-up was 29.9 months), persistent or recurrent disease was identified in 4 patients (33.3%) and none died from thyroid malignancy. Thyroid carcinomas disclosed by 18F-FDG-PET are associated with aggressive histological criteria likely to carry a worse prognosis.


Dietary specialization in mutualistic acacia-ants affects relative abundance but not identity of host-associated bacteria.
Acacia-ant mutualists in the genus Pseudomyrmex nest obligately in acacia plants and, as we show through stable isotope analysis, feed at a remarkably low trophic level. Insects with diets such as these sometimes depend on bacterial symbionts for nutritional enrichment. We, therefore, examine the bacterial communities associated with acacia-ants in order to determine whether they host bacterial partners likely to contribute to their nutrition. Despite large differences in trophic position, acacia-ants and related species with generalized diets do not host distinct bacterial taxa. However, we find that a small number of previously undescribed bacterial taxa do differ in relative abundance between acacia-ants and generalists, including several Acetobacteraceae and Nocardiaceae lineages related to common insect associates. Comparisons with an herbivorous generalist, a parasite that feeds on acacias and a mutualistic species with a generalized diet show that trophic level is likely responsible for these small differences in bacterial community structure. While we did not experimentally test for a nutritional benefit to hosts of these bacterial lineages, metagenomic analysis reveals a Bartonella relative with an intact nitrogen-recycling pathway widespread across Pseudomyrmex mutualists and generalists. This taxon may be contributing to nitrogen enrichment of its ant hosts through urease activity and, concordant with an obligately host-associated lifestyle, appears to be experiencing genomewide relaxed selection. The lack of distinctiveness in bacterial communities across trophic level in this group of ants shows a remarkable ability to adjust to varied diets, possibly with assistance from these diverse ant-specific bacterial lineages.


The influence of duration of circulatory arrest at 20 degrees C on cerebral changes.
In infants and piglets subjected to periods of circulatory arrest at 20 degrees C there was close correlation between duration of arrest and delay in return of electroencephalographic activity. Post mortem studies demonstrated histological evidence of brain damage in patients after circulatory arrest at 20 degrees C. Similar histological changes were demonstrated in piglets, including some who had complete E.E.G. and clinical recovery from circulatory arrest.


An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study.
Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention.


Guidelines for the management of hospitalized narcotics addicts.
Opiate-dependent patients who are hospitalized for medical, surgical, or obstetrical reasons require proper management of their addiction to care of their presenting illness. Guidelines are offered for methadone support during hospitalization for the patient enrolled in a treatment program and for the street addict. The important clinical features of withdrawal reactions are outlined, and a method is presented for establishing an initial and supportive dose of methadone for street addicts. The use of analgesics in the addicted patient, the treatment of methadone overdose, and some problems in the management of mixed-drug abuse are discussed.


Routine postoperative CT-scans after burr hole trepanation for chronic subdural hematoma - better before or after drainage removal?
To evaluate timing of scheduled CT-scans after burr hole trepanation for chronic subdural hematoma (cSDH). 131 patients with primary cSDH were included. Scheduled CT-scans were performed after burr hole trepanation and placement of a subdural drain. The influence of CT-scanning with or without indwelling drain was analysed regarding subsequent surgery and CT-scans, duration of hospitalization, short- and middle-term follow up by single factor analyses. Subgroup analyses were performed for patients receiving anticoagulant drugs. Median age was 74 years. Routine CT-scans with indwelling drainage were not shown to be beneficial regarding subsequent burr hole trepanations (p=0.243), craniotomies (p=1.000) and outcome at discharge (p=0.297). Mean duration of hospitalization (11 vs. 8 days, p=0.013) was significantly longer and number of subsequent CT-scans was higher when CT scan was performed with indwelling drain (2.3 vs. 1.4, p=0.001). In middle-term follow-up, beneficial effects of CT-scanning with inlaying drainage could neither be shown. Moreover, advantageous effects of CT-scans with indwelling drains could neither be shown for patients receiving anticoagulant drugs. Scheduled postoperative cranial imaging with indwelling drains was not shown to be beneficial and misses information of intracranial damage inflicted by removal of drains. We thus recommend CT-scanning after drainage removal.


Divalent Ytterbium Complex-Catalyzed Homo- and Cross-Coupling of Primary Arylsilanes.
Redistribution of primary silanes through C-Si and Si-H bond cleavage and reformation provides a straightforward synthesis of secondary silanes, but the poor selectivity and low efficiency severely hinders the application of this synthetic protocol. Here, we show that a newly synthesized divalent ytterbium alkyl complex exhibits unprecedentedly high catalytic activity toward the selective redistribution of primary arylsilanes to secondary arylsilanes. More significantly, this complex also effectively catalyzes the cross-coupling between electron-withdrawing substituted primary arylsilanes and electron-donating substituted primary arylsilanes to secondary arylsilanes containing two different aryls. DFT calculation indicates that the reaction always involve the exothermic formation of a hypervalent silicon upon facile addition of PhSiH3 to the Yb-E (E = C, H) bond. This hypervalent compound can easily either generate directly the Yb-Ph complex, or indirectly through the formation of Yb-H, that is the key complex for the formation of Ph2SiH2.


Compact and self-aligned all-optical image correlator based on third-harmonic generation.
We demonstrate a compact optical correlator using a diffractive optical element (DOE) beam splitter for 2D optical image processing. Image frequency conversion and correlation are demonstrated using third-harmonic generation (THG) in an organic film with a 1550 nm femtosecond laser. Spatial and temporal alignment of the femtosecond pulses are obtained by imaging the DOE onto the organic film.


The psoas muscle index as a predictor of mortality and morbidity of geriatric trauma patients: experience of a major trauma center in Kobe.
An association between the prognoses of trauma and sarcopenia has not been well documented. The purpose of this study was to compare the outcomes of elderly Japanese trauma patients with sarcopenia and those without sarcopenia. The medical records of patients aged ≧ 65 years old and Injury Severity Scores above 15 treated for trauma between 2010 and 2017 were reviewed, retrospectively. We measured the psoas muscle index (PMI), defined as the psoas muscle area at the third lumbar vertebra level divided by the body surface area. Patients of each gender with a PMI less than the lower interquartile range were included in the sarcopenia group. A questionnaire was mailed to the patients or their families to collect data on 1-year mortality and activities of daily living. There were 405 patients included in this study: 304 in the non-sarcopenia group (Group NS) and 101 in the sarcopenia group (Group S). Mortality was significantly higher in Group S than in Group NS (NS; 7.9% vs. S; 15.8%, OR, 2.20; 95% CI, 1.12-4.32; p = 0.027). Only 175 of the questionnaires were completed and the responses did not reveal any significant differences between the groups. Sarcopenia as defined by the PMI may be used as an indicator for mortality risk for geriatric trauma patients.


The Significance of Implementing Bilevel Positive Airway Pressure under Cluster Nursing in Improving the Survival Possibility of Patients with Severe Pulmonary Infection Complicated by Respiratory Failure.
To explore the significance of bilevel positive airway pressure (BIPAP) under cluster nursing in improving the survival probability of patients with severe pulmonary infection (SPI) complicated by respiratory failure (RF). This research included 153 SPI patients complicated by RF (SPI + RF) admitted between January 2020 and March 2022, including 55 cases in group A who were treated with BIPAP under cluster care during hospitalization, 47 cases in group B receiving invasive continuous mechanical ventilation during hospitalization, and 51 cases in group C treated with BIPAP under routine care during hospitalization. The three cohorts were compared regarding pre- and posttreatment serum inflammatory factors (IFs), blood gas (BG) parameters, heart rate (HR), and respiratory rate (RR). Besides, the cumulative time of ventilator use, successful ventilator weaning rate, mortality, and incidence of adverse events were counted. Finally, patients were scored for their psychological state using the Hamilton Anxiety/Depression Scale (HAMA/HAMD). The posttreatment TNF-α, IL-6, PCT, WBC, and PaCO2 reduced statistically in all the three groups, with the lowest levels found in group A and the highest in group B (P < 0.05); while PaO2 and SpO2 increased, with the highest values found in group A and the lowest in group B (P < 0.05). Among the three groups, group A had the shortest duration of ventilator use, the highest successful weaning rate, and the lowest incidence of adverse events (P < 0.05). Besides, HAMA and HAMD scores were the lowest in group A among the three groups, while those in group B were higher compared with group C (P < 0.05). The implementation of BIPAP under cluster nursing can effectively reduce inflammatory responses of SPI + RF patients, improve their vital signs, and enhance their psychological state, which has extremely high clinical application value.


Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: review of brain, cardiac, and limb malformations.
Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.


AEG-1 associates with metastasis in papillary thyroid cancer through upregulation of MMP2/9.
Astrocyte elevated gene-1 (AEG-1), known as an oncogene, is overexpressed in various cancers and implicated in tumor progression and metastasis. However, its functional significance and underlying molecular mechanisms in thyroid cancer remain to be elucidated. In the present study, we detected the potential function of AEG-1 in papillary thyroid cancer (PTC). We also investigated the relation between AEG-1 and matrix metalloproteases (MMP)2 and 9 through immunohistochemistry, western blotting, real-time PCR, immunofluorescence staining, zymography and co-immunoprecipitation (Co-IP). We found that overexpression of AEG-1 in PTC was positively correlated with lymph node metastasis and MMP2/9 expression. Knockdown of AEG-1 reduced the capacity of migration and invasion through downregulation of MMP2/9 in thyroid cancer cells. Furthermore, we firstly found that AEG-1 interacted with MMP9 in thyroid cancer cells. AEG-1 was associated with the activation of the nuclear factor κB (NF-κB) signaling pathways in thyroid cancer cells. Overall, our results for the first time showed that AEG-1 interacted with MMP9 in thyroid cancer cells and AEG-1 expression was closely associated with progression and metastasis of papillary thyroid cancer. AEG-1 might be a potential therapeutic target in papillary thyroid cancer.


[Comparative effectiveness of psychotropic drugs in patients with chronic ischemic heart disease].
As many as 348 courses of psychotropic and antianginal chemotherapy were performed for coronary disease confirmed angiographically. Hypochondriac patients were resistant to the drugs, depressive states and anxiety showed the best response. Tranquilizers and neuroleptic agents proved effective in anxiety, neuroleptics in cardiophobia and hypochondria, antidepressants in depression and asthenia. The addition of psychotropic drugs to antianginal therapy produced a positive effect on cardiac pain with antidepressants benefit ranking first, neuroleptics second and tranquilizers third. Being moderate and transient, treatment-related side effects did not cause the treatment discontinuation.


Leveraging finances for public health system improvement: results from the Turning Point initiative.
Reforming the public health infrastructure requires substantial system changes at the state level; state health agencies, however, often lack the resources and support for strategic planning and systemwide improvement. The Turning Point Initiative provided support for states to focus on large-scale system changes that resulted in increased funding for public health capacity and infrastructure development. Turning Point provides a test case for obtaining financial and institutional resources focused on systems change and infrastructure development-areas for which it has been historically difficult to obtain long-term support. The purpose of this exploratory, descriptive survey research was to enumerate the actual resources leveraged toward public health system improvement through the partnerships, planning, and implementation activities funded by the Robert Wood Johnson Foundation as a part of the Turning Point Initiative.


[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].
Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these responsibilities in clinical practice.


Factors influencing low incidence of living donors for renal transplantation in Poland.
To answer the question: "Why are only 3.8% of kidney transplantations in Poland from living donors?" The research was conducted using data from anonymous polls addressed to family members of dialyzed patients (potential donors). Almost everybody (98%) had heard about the possibility of treating renal insufficiency by kidney transplantation, but only 77% knew about the possibility of giving their own kidney to a related person. Merely 36% had been informed about this treatment method by a doctor. The most common fears within respondents were those of: health worsening after donating a kidney--45%, and the operation itself (taking an organ)--39%.


[Clinical and morphological characteristics of migrating erythema in patients with Ixodes tick-borne Lyme disease].
Patients with erythematous Ixodes tick-borne relapsing fever were examined and their skin biopsy specimens were morphologically studied to reveal clinical, immunological and morphological features of erythematous Ixodes tick-borne relapsing fever. Two types of development of erythema migrans were identified. These include 1) a typical type that appears as an area of homogenous hyperemia or that of annular shape and 2) an atypical one that presents as minor vesicles. There were elevated serum immunoglobulins A levels at the height of the disease. Morphologically, at the early stage of the disease, the center of erythema shows disturbances characterized by epidermal dystrophic processes, koilocytosis, subhorny and epidermal vesicles. The dermis displays solid perivascular lymphocytic infiltrates admixed with fibroblasts, fibrocytes, macrophages, plasmocytes, eosinophils, degranulated labrocytes. The interstitium exhibits scanty infiltrates. These changes are less pronounced at the periphery. Electron microscopy shows the structures morphologically similar to those of Borrelia. The late stage (days 15-23) of the disease is marked by insignificant dystrophy and perivascular fibrosis. There were no interstitial infiltrates. By and large, the pattern of clinical and immunological manifestations in patients with erythema migrans correlates with dermal morphological changes.


[The spatial dimension in health studies: a historical trajectory].
Focusing on concepts taken from critical geography, this article re-examines the spatial notions that were incorporated by the public health field between the late eighteenth and mid-twentieth centuries. Based on a review and systematization of intellectual production within the field of medical geography, this time span is broken into periods. We begin with a presentation of Finke's work (1792) and then move on to analyze the nineteenth century, when geography and medicine became scientific disciplines. The concept of space as a physical environment, with human action abstracted out, took hold within geography, while the biological-individual paradigm prevailed within the field of medicine. The text discusses the implications of the public health field's decision to embrace the geographic notions of determinism, type of life, and human ecology, and describes the contributions of Max Sorré and Pavlovsky. It also looks at the International Geographical Union's 1952 creation of a Commission on the Medical Geography of Health and illness and analyzes the emergence and coalescence of the 'new geography'.


Cryobanking Pluripotent Stem Cells.
Cryobanking human pluripotent stem cells (hPSCs), be they human embryonic (hESCs) or induced pluripotent stem cells (iPSCs), is essential for their use in research and cell-based therapeutics. Working and master cell banks can be generated with a desired level of quality assurance applied during cell freezing and storage. Conventional vitrification has evolved to more advanced control rate freezing, culminating in a myriad of published protocols with variable proficiencies and clinical efficacies. Notwithstanding, standardized and reliable protocols are necessary for basic science through to applied research and clinical product development. This chapter details several methods for hPSC cryopreservation, suitable for routine application, high-quality research, and adaptable for clinical compliance.


[Serologic profile of toxoplasmosis in pregnant women attended at a teaching-hospital in Recife].
To determine the serologic profile of toxoplasmosis and the main factors associated with susceptibility (patients without IgM and IgG antibodies) in pregnant women attended at a teaching-hospital in Recife, Brasil. A cross-sectional study was carried out, enrolling 503 pregnant women submitted to serology for toxoplasmosis at IMIP (Recife) from October 2004 to April 2005. Anti-Toxoplasma IgG and IgM antibodies were studied by IFA. A short questionnaire was administered to patients to provide identification, demographic and obstetrical characteristics, past history of morbidity, habits and dwelling conditions. The chi-square and Fisher-exact tests were used at a 5% level of significance. Immunity for toxoplasmosis was present in 74.7%, susceptibility in 22.5% and "possible" active infection in 2.8% of patients. No significant associations were observed between toxoplasmosis susceptibility and age, location, conditions of morbidity, habits, dwelling conditions and sewage system, living with animals, pregnancy and gestational age. A significant association between toxoplasmosis susceptibility and schooling was found, with a higher frequency of susceptibility among women with eight or more years of schooling. Susceptibility for toxoplasmosis was relatively low in these prenatal patients and schooling was the only identifiable predictive factor.