Multiplexing molecular diagnostics and immunoassays using emerging microarray technologies.
Enzyme-linked immunosorbent assays (ELISA) are frequently used for quantitative measurement of the presence of protein, for single-analyte testing, in a sample. The application of ELISA in a microarray format has the potential to simultaneously measure the presence and/or concentrations of numerous proteins, in multiplex testing, all contained in a small drop of test fluid. Microspot microarray technology, in combination with protein biomarkers and nucleic acid diagnostics, appears to be the future high-performance analytical platform of choice. Validation of a large number of disease markers in both molecular and protein diagnostics has paved the way for the emergence of the multiplex assay. Initially, simple low-throughput multiplex assays were tested using the immunoassay format. These were followed by low-level multiplexing and high-throughput array-based immunoassays. More recently, two types of high-level multiplexing and high-throughput diagnostic methods using microspot arrays and bead arrays have been successfully developed to complement single-analyte assays. The value in rapid diagnostic evaluation for high-throughput multiplex, diagnostic test systems based on sound assay design must take into account data screening, normalization and statistical evaluation of possible concentration measurement, data errors and automated operation. Benefits of using multiplex array platforms include improved-quality patient care, as well as cost effectiveness and time saving. These multiplex methods also set the stage for future protein/nucleic acid codetection. Currently, the one analyte at a time test scheme is still dominant; nonetheless, the multiplex microspot microarray tests evaluated in a single multiassay analyzer are expected to become a significant part of clinical diagnostic testing within the next 5-10 years. This review is focused on microspot array and bead array methods for providing high throughput and a high degree of multiplexing in diagnostic testing.


Distal anterior interosseous nerve transfer to the deep motor branch of the ulnar nerve for reconstruction of high ulnar nerve injuries.
Proximal ulnar nerve injuries can result in loss of intrinsic muscle function of the hand, and distal nerve transfers provide nerve coaptation close to the target muscle. This retrospective chart review evaluated patient outcome following a distal nerve transfer of the anterior interosseous nerve (AIN) to the deep motor branch of the ulnar nerve. There were eight patient charts reviewed, three women, and five men. The mean patient age was 38 years (standard deviation: 22 years). The mean time from injury to surgery was 3 months (standard deviation: 3 months), and mean postoperative follow-up time was 18 months (standard deviation: 11 months). All patients had reinnervation of the ulnar nerve intrinsic hand muscles with improved postoperative lateral pinch and grip strength. One patient had a secondary tendon transfer. No functional deficit in performing tasks in pronation was reported. The distal nerve transfer of the AIN to the deep motor branch of the ulnar nerve provides good reinnervation of the ulnar-nerve-innervated intrinsic muscles of the hand.


Characterization of H-2Db antigens implies haplotype differences in the number of H-2 molecules expressed.
Investigation of the molecular heterogeneity of H-2Db region antigens by using monoclonal antibodies and complex alloantisera has yielded evidence for the existence of only one gene product in this region. Sequential immunoprecipitation and isoelectric focusing analysis suggest that the private H-2.m2 and public H-2.m64 specificities defined by monoclonal or alloantibodies are present on the same molecule. Blocking studies with these reagents indicate these specificities represent two determinants spatially separated on the H-2Db molecule. Functional studies suggest that effector T cells may be generated against both of these determinants or closely associated epitopes, but the majority of the T cells recognize an epitope associated with or identical to the private specificity H-2.m2. Studies of the D region-encoded products of haplotypes besides H-2b have shown two or more distinct molecules can be detected by anti-H-2.m64 in both the H-2d and H-2q haplotypes. The presence of H-2.m64 on a single Db molecule is unique and gives further evidence for the lack of other gene products encoded in this region. Speculations based on the molecular heterogeneity of the D region gene products are made concerning the evolution and genetic organization of H-2 genes.


Developing a Relevant Taxonomy to Assess Dental School Clinic Patient Complaints.
The aims of this study were to categorize and analyze the most frequent patient complaints at the Rutgers School of Dental Medicine (RSDM) clinic in an effort to identify areas in need of improvement. A retrospective review of patient complaints reported to the RSDM Office for Clinical Affairs from July 1, 2011 to June 30, 2015 was conducted. A total of 148 unduplicated patients were selected for evaluation because they made at least one official complaint. In total, 193 patient complaints were made during this period. A published complaint taxonomy was used to categorize RSDM patient complaints into domains, categories, and subcategories, highlighting frequent issues of complaint. Of the 193 complaints made, 256 issues were identified. The results showed that the most frequent domain of complaint was Management, followed by Clinical, then Relationships. Institutional Issues and Quality were the most recurring categories coded. Of the 26 subcategories, nearly 70% of the complaints were coded into one of four: Finance and Billing, Delays, Patient Journey, and Quality of Care. While the results were effective in identifying broad areas of improvement, there were limitations to using the traditional taxonomy in the dental school setting. Based on these data, the RSDM Patient Complaint Taxonomy, specific to the needs of a dental school environment, was created in an effort to gain increased specificity and further enhance quality improvement measures. It is the hope of the research team that this tool will be used across dental schools, opening the door for future collaborations and ultimately improving patient care.


Comparison of Public Health Containment Measures of COVID-19 in China and India.
This study aimed to make a comparative analysis of the public health containment measures between China and India, explore the causes of the serious COVID-19 epidemic in India, and eventually to improve global infectious disease control. We extracted publicly available data from official websites, summarized the containment measures implemented in China and India, and assessed their effectiveness. China has responded to the COVID-19 outbreak with strict public health containment measures, including lockdown of Wuhan city, active case tracing, and large-scale testing, ultimately preventing a large increase in daily new cases and maintaining a low mortality rate per million population (as of May 5, 2021, daily new cases were 11 and mortality rate per million population was 3.37). India, although imposing a national lockdown to control the pandemic, has not implemented strict testing, tracking, and quarantine measures due to the overburdened healthcare system. Combined with massive lockdown, it has accelerated human mobility and exacerbated the epidemic, resulting in a rapid increase in daily new cases and a high mortality rate per million population (as of May 5, 2021, daily new cases were 412,431 and mortality rate per million population was 166.79). China and India implemented public health containment measures to contain the spread of the COVID-19 pandemic based on their national situations. Meanwhile, daily new cases and mortality of COVID-19 also were affected by environmental and socioeconomic. Countries make a comprehensive strategy not only in terms of the biological, pharmaceutical, health, and sanitation sectors but also based on sustainability science and environmental science.


Computer-assisted three-dimensional planning in craniofacial surgery.
Three-dimensional surface reconstruction from computed tomographic (CT) data has been used to plan craniofacial operations. Cephalometric and anthropometric databases were integrated with three-dimensional CT reconstructions to quantitate the skeletal deformity and to assist in the design of the surgical procedure. Interactive techniques were developed to simulate osteotomies and skeletal movements in three dimensions on the computer-generated surface images. The ocular globes were referenced to position the orbital segments; i.e., the osteotomized segments were transposed into normal anatomic relationship with respect to the eyes. The measurements from the computer graphic simulation were used intraoperatively to establish the correct position of the skeletal segments.


[Development of an algorithm for the appointment of biofeed-back therapy and Cytoflavin for the treatment of osteochondrosis in elderly patients.]
Continuous improvement of protocols for the treatment of various ailments, in particular, osteochondrosis, is one of the important tasks of providing medical care to elderly patients. Supplementation of treatment with Cytoflavin and biofeed-back therapy seems to be a promising solution, however, it is necessary to develop an algorithm to predict it effectiveness in patients taking into account their initial clinical and psychophysiological status. As a result of the treatment, predictors of the effectiveness of the use of Cytoflavin and biofeed-back therapy have been identified and an algorithm for their administration has been developed.


Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas.
Forty-one consecutive patients with supratentorial primary brain tumors (38 Grade III and IV astrocytomas, one giant-cell astrocytoma, and two cases with insufficient tissue for diagnosis) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups. Group 1 (15 patients) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks. Group 2 (13 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea CCNU) 130 mg/sq m orally every 6 weeks. Group 3 (13 patients) received radiation therapy plus CCNU as for Groups 1 and 2. When the disease progressed, patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively. The median survival time in these groups was 188, 259, and 252 days, and the mean survival 263, 262, and 329 days. The median time from diagnosis to crossover (Groups 1 and 2) or to progression (Group 3) was 163, 99, and 220 days, and the mean time was 172, 108, and 231 days. There was no statistically significant difference between the means or medians in any of these situations.


Could Moesin Be a New Marker for Indicating Progression in Endometrial Cancer?
This study aims to determine an important parameter in progression from pre-invasive lesions of endometrium to endometrial cancer and also evaluate the effect of this parameter on the progression of endometrial cancer. In our study,30 patients with normal endometrial tissue (group 1), 56 patients who had endometrial hyperplasia without atypia (group 2), 36 patients who had endometrial hyperplasia with atypia (group 3), and 63 patients with endometrial cancer (group 4) were included. Age, parity, body-mass index, systemic diseases, and tumor markers of patients were evaluated. Expression levels of Ezrin, Radixin, and Moesin proteins were immunohistochemically evaluated in terms of frequency, intensity, and score value. When we compared hyperplasia cases with or without atypia; frequency, and score value of ezrin expression and frequency, intensity, and score value of moesin expression was significantly higher in patients who had hyperplasia with atypia (p:0.000 p:0.001 p:0.003, p:0.032 p: 0.035 p:0.015 p:0.005, respectively). It was observed that the frequency and score value of moesin expression were significantly higher in patients with endometrial cancer when compared with patients who had hyperplasia with atypia (p:0.003 p:0.045). The frequency of moesin expression was significantly higher in patients who had postoperative mortality (p:0.030 p:0.039). Increased frequency of moesin expression in the preoperative period in patients with atypical hyperplasia should alert the surgeon in terms of malignancy. If the frequency of moesin expression increases in cases with endometrial cancer, the patient should be followed closely in terms of progression in the postoperative period.


The influence of hyperoxic ventilation during sodium nitroprusside-induced hypotension on skeletal muscle tissue oxygen tension.
Increasing inspired oxygen concentrations might provide a simple and effective intervention to increase oxygen tension in tissues during controlled hypotension. To test this hypothesis, the influence of hyperoxic ventilation (100% O2) on skeletal muscle oxygen partial pressure (Ptio2) in patients receiving sodium nitroprusside-induced controlled hypotension was studied. Forty-two patients undergoing radical prostatectomy were prospectively studied and randomly divided into three groups as follows: (1) Controlled hypotension induced by sodium nitroprusside (mean arterial blood pressure, 50 mmHg) and hyperoxic ventilation (CH-100%; n = 14); (2) controlled hypotension and ventilation with 50% O2 in nitrous oxide (CH-50%; n = 14); and (3) standard normotensive anesthesia with 50% O2 in nitrous oxide (control; n = 14). Ptio2 values were measured continuously in all patients using implantable polarographic microprobes. Arterial blood gases and lactate concentrations were analyzed in 30-min intervals. Surgical blood loss and transfusion requirements were significantly reduced in both groups receiving hypotensive anesthesia. During surgery, arterial partial pressure of oxy-gen and arterial oxygen content were significantly higher in patients of the CH-100% group. Baseline values of Ptio2 were comparable between the groups (CH-50%: 25.0 +/- 0.7 mmHg; CH-100%: 25.2 +/- 0.2 mmHg; control: 24.5 +/- 0.2 mmHg). After a transient increase in Ptio2 in the CH-100% group during normotension, Ptio2 values returned to baseline and remained unchanged in the control group. Ptio2 decreased significantly during the hypotensive period in the CH-50% group. The lowest mean Ptio2 values were 15.0 +/- 4.1 mmHg in the CH-50% group, 24.2 +/- 4.9 mmHg in the CH-100% group, and 23.5 +/- 3.8 mmHg in the control group. There were no significant changes in lactate plasma concentrations in any group throughout the study period. Hyperoxic ventilation improved skeletal muscle tissue oxygenation during sodium nitroprusside-induced hypotension. This improved local tissue oxygenation seems to be most likely due to an increase in convective oxygen transport and the attenuation of hyperoxemia-induced arteriolar vasoconstriction by sodium nitroprusside.


Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation.
Homeodomain only protein, Hop, is an unusual small protein that modulates target gene transcription without direct binding to DNA. Here we show that Hop interacts with Enhancer of Polycomb1 (Epc1), a homolog of a Drosophila polycomb group gene product that regulates transcription, to induce the skeletal muscle differentiation. Yeast two-hybrid assay with the human adult heart cDNA library revealed that Hop can associate with Epc1. The amino-terminal domain of Epc1 as well as full Epc1 physically interacted with Hop in mammalian cells and in yeast. Epc1 is highly expressed in the embryonic heart and adult skeletal muscles. Serum deprivation induced differentiation of H9c2, a myoblast cell line, into skeletal myocytes, and Epc1 was up-regulated. Differentiation of H9c2 was induced by Epc1 overexpression, although it was severely impaired in Epc1-knockdown cells. Co-transfection of Hop potentiated Epc1-induced transactivation of myogenin and myotube formation. Hop knock-out mice elicited a decrease in myosin heavy chain and myogenin expressions in skeletal muscle and showed delay in hamstring muscle healing after injury. Differentiation was impaired in skeletal myoblasts from Hop knock-out mice. These results suggest that Epc1 plays a role in the initiation of skeletal muscle differentiation, and its interaction with Hop is required for the full activity.


Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
Histidine triad nucleotide-binding protein (HINT), a dimeric purine nucleotide-binding protein from rabbit heart, is a member of the HIT (histidine triad) superfamily which includes HINT homologues and FHIT (HIT protein encoded at the chromosome 3 fragile site) homologues. Crystal structures of HINT-nucleotide complexes demonstrate that the most conserved residues in the superfamily mediate nucleotide binding and that the HIT motif forms part of the phosphate binding loop. Galactose-1-phosphate uridylyltransferase, whose deficiency causes galactosemia, contains tandem HINT domains with the same fold and mode of nucleotide binding as HINT despite having no overall sequence similarity. Features of FHIT, a diadenosine polyphosphate hydrolase and candidate tumour suppressor, are predicted from HINT-nucleotide structures.


[Action of testicular hyaluronidase on macromolecules of the cutaneous extracellular matrix. Study by computerized image analysis].
The aim of this work was to precise the action of testicular hyaluronidase (Thiomucase, Millot Solac, Sanofi, France) on the extracellular matrix macromolecules of the skin in an experimental animal model. Intradermal injection of hyaluronidase in the rabbit acts on proteoglycans which are degraded. Collagen bundles are dissociated. This is due to endoglycosaminidase activity of the hyaluronidase on dermal proteoglycans. The network of the elastic fibers was not altered by the enzyme injections, this suggest the absence of elastolytic activity in the Thiomucase preparations. The dissociation of collagen bundles and the degradation of proteoglycans are followed by the resynthesis of the initially degraded proteoglycans. The observed morphological changes which follow the intradermal injection of hyaluronidase, confirm the ability of this enzyme to influence the composition and the structure of the dermis.


Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogens.
Dendritic cells produce cytokines that regulate the class of the adaptive immune response. Microbial recognition is mediated, at least in part, by pattern recognition receptors such as Toll-like receptors, which influence dendritic cell maturation. In humans it is not yet clear how intact pathogens modulate the developing immune response. To address the effects of intact pathogens on the maturation and effector functions of human dendritic cells, we investigated their responses to a number of microbial pathogens. We studied a range of micro-organisms including Gram-negative bacteria (Escherichia coli and Salmonella enterica sv. typhimurium), Gram-positive cocci (Staphylococcus aureus) and atypical bacteria (Mycobacterium tuberculosis and Mycoplasma hominis) as well as the human protozoal parasite Trichomonas vaginalis. The micro-organisms were fixed in formaldehyde to prevent replication whilst preserving surface morphology. All the pathogens induced similar up-regulation of dendritic cell activation-associated cell surface markers but there was a profound difference in the patterns of cytokines produced by the stimulated dendritic cells. Some pathogens (E. coli, Salmonella enterica sv. typhimurium and S. aureus) induced interleukin-12 (IL-12), IL-10 and interferon-alpha whereas others (M. tuberculosis, Mycoplasma hominis and T. vaginalis) induced only IL-10. This differential effect was not altered by costimulation of the dendritic cells through CD40. These results support the notion that human dendritic cells are plastic in their response to microbial stimuli and that the nature of the pathogen dictates the response of the dendritic cell.


The prevalence of masked hypertension in relation to cigarette smoking in a Chinese male population.
Smokers may smoke cigarettes during ambulatory or home blood pressure (BP) monitoring but not clinic measurement. We investigated the prevalence of masked hypertension in relation to cigarette smoking in Chinese outpatients enrolled in a multicenter registry. Our study included 1646 men [494 (30.0%) current smokers]. We defined masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and elevated daytime (≥135/85 mmHg) or night-time (≥120/70 mmHg) ambulatory or morning or evening home SBP/DBP (≥135/85 mmHg). In all men, multiple logistic regression showed that current cigarette smoking was significantly associated with daytime [prevalence 18.7%, odds ratio (OR) 1.69, 95% confidence interval 1.27-2.25, P = 0.0003] but not night-time (prevalence 27.1%, P = 0.32) ambulatory masked hypertension and associated with evening (prevalence 14.6%, OR 1.81, confidence interval 1.33-2.47, P = 0.0002) but not morning (prevalence 17.6%, P = 0.29) home masked hypertension. The associations were more pronounced for heavy smoking (≥20 cigarettes/day) relative to never smoking for both masked daytime ambulatory (OR 1.97, P = 0.001) and evening home hypertension (OR 2.40, P < 0.0001) or in patients over 55 years of age (P for interaction in relation to daytime ambulatory masked hypertension = 0.005). In men with clinic normotension (n = 742), the associations were also significant (P < 0.01), particularly in those with a normal to high-normal clinic BP (n = 619, P < 0.04). Cigarette smoking was associated with increased odds of masked daytime ambulatory and evening home hypertension, especially in heavy smoking or older men.


Complex pelvic fracture urethral distraction defects revisited.
This study aimed to establish some guidelines for the definition, diagnosis and treatment of complex pelvic fracture urethral distraction defects (PFUDD). A total of 40 patients with complex PFUDD was enrolled in this study. Urethral defects were associated with a paraurethral bladder base fistula (PBBF) (six patients), urethrorectal fistula (eight), urethrocutaneous fistula (nine), urinoma cavity (eight) or bladder neck incompetence (nine). In four patients the urethra had been wrongly reconstructed into a bladder base fistula (three) or urinoma cavity (one), elsewhere. Repair was performed by a perineal anastomotic urethroplasty in 15 patients and by a perineoabdominal transpubic procedure in 25. Repair was successful in nine out of 15 (60%) patients who received a perineal repair and in 23 out of 25 (92%) who underwent a perineoabdominal transpubic procedure. Of the eight patients with unsuccessful outcomes five were successfully recorrected by transpubic urethroplasty. A PFUDD may be considered as complex if it is associated with a PBBF, urethrorectal or urethrocutaneous fistula, urinoma cavity, or bladder neck incompetence. Complete excision of a PBBF usually requires a perineoretropubic approach. The initial trauma-related urethrorectal fistula usually opens into the prostatic urethra and its repair requires an abdominal approach, whereas an iatrogenic rectal fistula usually opens into the proximal bulbar urethra and can be resolved by a relatively simple perineal operation. Excision of a urinoma cavity or urethrocutaneous fistula can usually be accomplished from the perineum, while repair of a bladder neck incompetence requires an abdominal approach.


Two new orthoclad species from Colombian Andes (Diptera: Chironomidae).
Lipurometriocnemus. bogotensis sp. n. and Antillocladius laviejae sp. n., two species collected at the "La Vieja" creek, near Bogotá, Colombia; 2666 m, are described and depicted as male imagines. L. bogotensis sp. n. can be separated from other Lipurometriocnemus species by lacking acrosticals setae on thorax, thus an emendation of the genus concept is presented. Antillocladius laviejae sp. n. is differentiated from other closely related members of the genus mainly by the pilosity of wings.


Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum.
Two hundred and eighty patients with previously untreated large bowel adenocarcinoma were retrospectively evaluated following complete primary resection to determine patterns of recurrence. One hundred and five patients (37%) subsequently developed recurrent disease. Sixty percent (63/105) presented with local recurrence alone, 14% (15/105) with concomitant local recurrence and distant metastases, and 26% (27/105) with distant metastases alone. Ninety-two percent of local recurrences developed in structures contiguous to the operative area of the incision. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through 5 years, local recurrence without clinical evidence of distant metastases was the most common cause of death. Plans for adjuvant radiation therapy are discussed.


Activity of hexokinase is increased by its interaction with hepatitis C virus protein NS5A.
The study of cellular central carbon metabolism modulations induced by viruses is an emerging field. Human cytomegalovirus (HCMV), herpes simplex virus (HSV), Kaposi's sarcoma-associated herpesvirus (KSHV), and hepatitis C virus (HCV) have been shown recently to reprogram cell metabolism to support their replication. During HCV infection the global glucidolipidic metabolism of hepatocytes is highly impacted. It was suggested that HCV might modify glucose uptake and glycolysis to increase fatty acids synthesis, but underlying mechanisms have not been completely elucidated. We thus investigated how HCV may modulate glycolysis. We observed that in infected Huh7.5 cells and in subgenomic replicon-positive Huh9.13 cells, glucose consumption as well as lactate secretion was increased. Using protein complementation assays and coimmunoprecipitation, we identified a direct interaction between the HCV NS5A protein and cellular hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis. NS5A expression was sufficient to enhance glucose consumption and lactate secretion in Huh7.5 cells. Moreover, determination of HK activity in cell homogenates revealed that addition of exogenous NS5A protein, either the full-length protein or its D2 or D3, but not D1, domain, was sufficient to increase enzyme activity. Finally, determination of recombinant HK2 catalytic parameters (V(max) and K(m)) in the presence of NS5A identified this viral protein as an activator of the enzyme. In summary, this study describes a direct interaction between HCV NS5A protein and cellular HK2 which is accompanied by an increase in HK2 activity that might contribute to an increased glycolysis rate during HCV infection. Substantial evidence indicates that viruses reprogram the central carbon metabolism of the cell to support their replication. Nevertheless, precise underlying mechanisms are poorly described. Metabolic pathways are structured as connected enzymatic cascades providing elemental biomolecular blocks necessary for cell life and viral replication. In this study, we observed an increase in glucose consumption and lactate secretion in HCV-infected cells, revealing higher glycolytic activity. We also identified an interaction between the HCV NS5A nonstructural protein and cellular hexokinase 2, the first rate-limiting enzyme of glycolysis. This interaction results in an enhancement of catalytic parameters of the enzyme, which might explain, at least in part, the aerobic glycolysis shift observed in HCV-infected cells.


Improved diagnosis of childhood tuberculous meningitis using more than one nucleic acid amplification test.
Early treatment is critical to reducing tuberculous meningitis (TBM) related morbidity and mortality. Diagnosis based on cerebrospinal fluid (CSF) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. Enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children. We assessed the diagnostic accuracy of the GenoType(®) MTBDRplus and Xpert(®) MTB/RIF assays on CSF collected from paediatric meningitis suspects prospectively enrolled at Tygerberg Hospital, Cape Town, South Africa. Fluorescent auramine-O microscopy, liquid culture for Mycobacterium tuberculosis, GenoType and Xpert assays were performed on all CSF samples. Of 101 meningitis suspects, 55 were diagnosed with TBM and 46 served as non-TBM controls. Using a pre-defined TBM case definition as reference standard, sensitivities and specificities were 4% and 100% for fluorescent microscopy, 22% and 100% for culture, 33% and 98% for GenoType, 26% and 100% for Xpert, 22% and 100% for microscopy and culture combined and 49% and 98% for GenoType and Xpert combined. Culture, GenoType and Xpert combined performed best, with 56% sensitivity and 98% specificity. Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.


Combination therapy of anabolic and nonbisphosphonates antiresorptive agents for the treatment of osteoporosis: A meta-analysis.
According to the mechanisms of action, combination therapy of anabolic and antiresorptive agents may produce more effect for the treatment of osteoporosis. However, the combination therapy of anabolic agents and bisphosphonates reports no benefit and even reduced the anabolic effects of anabolic agents. This study aims to assess the effect of combination therapy of anabolic and nonbisphosphonates antiresorptive agents in adults with osteoporosis. Medline, EMBASE, and Cochrane Library were searched from January 1, 1980 to November 1, 2017 for randomized controlled trials (RCTs) of adults with osteoporosis treated in combination therapy of anabolic and nonbisphosphonates antiresorptive agents compared with monotherapy of either agent alone. The primary outcome was the incidence of fractures. The secondary outcomes were the bone mineral density (BMD) changes at lumbar spine and total hip. Continuous outcomes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI), while dichotomous outcomes were expressed as risk ratio (RR) and 95% CI. The meta-analysis was performed using a random-effects model. I statistic (I > 50% as a threshold indicates significant heterogeneity) was used to assess the heterogeneity. A total of 10 trials with a total of 1042 patients were included. The pooled results showed that the combination therapy demonstrated a significant advantage over a monotherapy in the BMD improvement at the lumbar spine (SMD 1.18; 95% CI, 0.63 to 1.72; I = 93%) and the total hip (SMD 0.89; 95% CI, 0.48 to 1.29; I = 88%) and further reduce the fracture risk (RR, 0.45; 95%CI, 0.21 to 0.94; I = 0%). Low-to-moderate-quality evidence shows that the combination therapy of anabolic and nonbisphosphonates antiresorptive agents is superior to monotherapy in improving the BMD and reducing the fracture risk. However, further high methodological quality studies are needed to determine the antifracture efficacy, cost-effectiveness and safety of this strategy of combination therapy.


Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients.
Prostate cancer is the second most common cancer in men in the United States, and racial disparities are greatly observed in the disease. Specifically, African American (AA) patients have 60% higher incidence and mortality rates, in addition to higher grade and stage prostate tumors, than European American (EA) patients. In order to narrow the gap between clinical outcomes for these two populations, genetic and molecular signatures contributing to this disparity have been characterized. Over the past decade, profiles of prostate tumor samples from different ethnic groups have been developed using molecular and functional assays coupled with next generation sequencing or microarrays. Comparative genome-wide analyses of genomic, epigenomic, and transcriptomic profiles from prostate tumor samples have uncovered potential race-specific mutations, copy number alterations, DNA methylation, and gene expression patterns. In this study, we reviewed over 20 published studies that examined the aforementioned molecular contributions to racial disparities in AA and EA prostate cancer patients. The reviewed genomic studies revealed mutations, deletions, amplifications, duplications, or fusion genes differentially enriched in AA patients relative to EA patients. Commonly reported genomic alterations included mutations or copy number alterations of FOXA1, KMT2D, SPOP, MYC, PTEN, TP53, ZFHX3, and the TMPRSS2-ERG fusion. The reviewed epigenomic studies identified that CpG sites near the promoters of PMEPA1, RARB, SNRPN, and TIMP3 genes were differentially methylated between AA and EA patients. Lastly, the reviewed transcriptomic studies identified genes (e.g. CCL4, CHRM3, CRYBB2, CXCR4, GALR1, GSTM3, SPINK1) and signaling pathways dysregulated between AA and EA patients. The most frequently found dysregulated pathways were involved in immune and inflammatory responses and neuroactive ligand signaling. Overall, we observed that the genomic, epigenomic, and transcriptomic alterations evaluated between AA and EA prostate cancer patients varied between studies, highlighting the impact of using different methods and sample sizes. The reported genomic, epigenomic, and transcriptomic alterations do not only uncover molecular mechanisms of tumorigenesis but also provide researchers and clinicians valuable resources to identify novel biomarkers and treatment modalities to improve the disparity of clinical outcomes between AA and EA patients.


Pancreatic lysosomal enzyme secretion is changed by hepatectomy in rats.
To explore the effect of hepatectomy on the secretion of lysosomal enzymes into the pancreatic juice when stimulated by gut hormones, we evaluated the cerulein-stimulated amylase output and cathepsin B output into pancreatic juice, the amylase and cathepsin B content in pancreatic tissue, and the distribution of cathepsin B in acinar cells in the regenerating (4 days) and recovering (8 days) stages after about 70% hepatectomy in rats. Amylase output was significantly higher after hepatectomy than in the control groups. Cathepsin B was secreted into the pancreatic juice after stimulation by cerulein in both the control and the hepatectomized groups, but, particularly 4 days after hepatectomy, cathepsin B output was significantly higher than in the controls, and in the acinar cells redistribution of cathepsin B was found. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the amylase content in pancreatic tissue was significantly greater in the hepatectomized than in the control rats, but the cathepsin B content did not show any significant change. These results indicate that cerulein can stimulate the secretion of lysosomal enzyme into the pancreatic juice, as it does the secretion of digestive enzymes. Moreover, it appears that the synthesis and secretion of amylase in and from the acinar cells is increased after hepatectomy and that a redistribution of lysosomal enzyme occurs in the acinar cells.


The sequence of pituitary responses to synthetic luteinizing hormone releasing hormone (LH-RH) throughout the normal menstrual cycle.
Thirty-one ovulatory women between 20 and 33 years of age were given 150 mug of synthetic LH-RH during different phases of the menstrual cycle. Five patients were studied during the early follicular phase (days 4-7); 10 patients during the late follicular phase (days 9-12); 6 patients during the "LH Surge"; 5 patients during the early luteal phase (days 14-16); 3 patients during mid-luteal phase (days 17-21); and 2 patients during late luteal phase (days 22-27). Oestrogen, progesterone, FSH and LH levels were determined from 30 min prior to LH-RH administration to 90 min thereafter in all cases. LH response to LH-RH increased progressively during the follicular phase. Enhanced pituitary responsiveness to LH-RH occurred at mid-cycle for both LH and FSH and maximum LH responses occurred during the "LH Surge" and early luteal phase. LH responses during the mid and late luteal phases were similar to late follicular phase responses. There were no significant differences between FSH responses during the early follicular, late follicular, mid-luteal and late luteal phases. Maximum pituitary responsiveness appears to occur in a gonadal steroid milieu of high oestrogen levels in association with rising but low progesterone levels. Progesterone or a crucial oestrogen: progesterone ratio may in fact potentiate pituitary release of LH during the early stages of corpus luteum formation. Pituitary responsiveness to LH-RH correlates positively with basal LH and oestrogen levels during the menstrual cycle and with the oestrogen:progesterone ratio during the luteal phase.


Effect of Void Defects on the Indentation Behavior of Ni/Ni3Al Crystal.
Inconel 718 (IN 718) superalloys are widely used as engineering materials owing to their superior mechanical performance. And voids are unavoidable defects in IN 718 superalloy preparation, which dramatically affect the mechanical properties of IN 718 superalloys. In this work, the effects of void radius, distance from the top of the void to the substrate surface, and substrate temperature on the mechanical properties of the Ni/Ni3Al crystal are systematically investigated. It is shown that voids affect the formation of stair-rod dislocations and Shockley dislocations in the substrate, which in turn determines the mechanical properties. Thus, with the increase in void radius, Young's modulus and hardness gradually decrease. With the increase in void distance, Young's modulus and hardness increase and finally tend to be stable. In addition, the increase in substrate temperature leads to the interphase boundary becoming irregular and increases the defects in the γ and γ″ phases. As a result, Young's modulus and hardness of the substrate decrease. This work aims to provide a guideline for investigating the indentation properties of Ni-based superalloys using MD.


Transitions in dementia care: theoretical support for nursing roles.
There are several predictable transitions in the course of dementia, and care is often provided by family members in the earlier stages. Later stages often include the move to one or more care settings. Important transitions for those with dementia and their families and/or caregivers include the initial diagnosis of dementia; advanced planning for financial concerns and healthcare considerations; driving cessation; managing behavioral symptoms; changes in settings; and preparing for end-of-life. Evidence has emerged to inform the important roles nurses may have in each of the transitions. In this article, we explore the concept of transitional care and how it relates to nursing care of older adults with Alzheimer's disease and other dementias. We begin by briefly describing a middle-range theory of transitions. Next, we describe the dementia trajectory and provide evidence for expanding nursing roles in transitions. Also included are recommendations for research in the area of roles and transitional care.


How Accurate Is Density Functional Theory at Predicting Dipole Moments? An Assessment Using a New Database of 200 Benchmark Values.
Dipole moments are a simple, global measure of the accuracy of the electron density of a polar molecule. Dipole moments also affect the interactions of a molecule with other molecules as well as electric fields. To directly assess the accuracy of modern density functionals for calculating dipole moments, we have developed a database of 200 benchmark dipole moments, using coupled cluster theory through triple excitations, extrapolated to the complete basis set limit. This new database is used to assess the performance of 88 popular or recently developed density functionals. The results suggest that double hybrid functionals perform the best, yielding dipole moments within about 3.6-4.5% regularized RMS error versus the reference values-which is not very different from the 4% regularized RMS error produced by coupled cluster singles and doubles. Many hybrid functionals also perform quite well, generating regularized RMS errors in the 5-6% range. Some functionals, however, exhibit large outliers, and local functionals in general perform less well than hybrids or double hybrids.


[Study of the effect of combination therapy of human granulocyte-colony stimulating factor (G-CSF) and amikacin on experimental pyelonephritis induced by Pseudomonas aeruginosa in neutropenic mice].
We reported the prophylactic and therapeutic effect of human granulocyte-colony stimulating factor (G-CSF) on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group). In the cyclophosphamide-treated neutropenic mice, the prophylactic administration of G-CSF (2 micrograms/day/mouse) yielded a lower incidence of infection than that of saline alone. However, the therapeutic administration of G-CSF (2 micrograms/day/mouse) did not produce decreases of the rate, suggesting that this type of administration had no effect on infection. Thus, we investigated the effect of the combination therapy of G-CSF and Amikacin. In neutropenic mice, the therapeutic administration of G-CSF alone and Amikacin (20 mg/kg) alone did not produce decreases of incidence of infection. But, combination administration of these yielded a lower incidence of infection. These results suggest that synergy of bactericidal effects of neutrophils accelerated by G-CSF with Amikacin, and a combination of these have a therapeutic effect on bacterial infection in neutropenic mice.


[Parathormone and left ventricular hypertrophy].
In order to examine the relation between secondary hyperparathyroidism (sHPT) and left ventricular hypertrophy (LVH) in hemodialysis (HD) patients, were selected retrospectively 60 of 228 HD patients who had two echocardiography over a 12-16 months period (13.2 1.2 months). Patients were subdivided in three groups (G) according to PTH behaviour: G1 (n = 19), with PTH levels < 300 pg/ml not requiring with vitamin D receptor activators (VDRAs) treatment; G2 (n = 20), with a progressive increase of PTH levels to values > 300 pg/ml that required to start or to increase VDRAs therapy in 18/20 patients during follow-up; G3 (n = 21), with PTH levels > 300 pg/ml and > 50% reduction after VDRAs treatment. Parathormone levels correlated with left ventricular mass index (LVMi; r = 0.714; P < 0.001). Multiple regression analysis indicated that PTH levels were an independent predictor of LVMi (P < 0.001). Patients with baseline PTH levels > 300 pg/ml (n = 27) had higher LVMi with respect to those with PTH < 300 pg/ml (n=33), 197 50 vs 136 30 g/m2 (P < 0.01). In G1 LVMi did not change during follow-up. In G2 LVMi increased from 146 26 to 169 35 g/m2 (P=NS). In G3LVMi decreased from 210 44 to 154 42 g/m2 (P < 0.05). Parathyroid hormone seems to play an important role in the genesis and perpetuation of LVH, whereas treatment of sHPT with VDRAs may determine LVH regression or at least slow down its progression.


Vesicular stomatitis.
More than 800 premises in eight states in the USA have recently reported cases of vesicular stomatitis in their horses. Here, Peter Timoney, of the Gluck Equine Research Center in Kentucky, discusses this zoonotic disease in more detail.


Anti-GM2 antibody positive Guillain-Barré syndrome presenting with ataxia in a pediatric patient: An atypical manifestation.
Guillain-Barré syndrome (GBS) is the most prevalent cause of acquired paralytic neuropathy in children, however, ataxia as the initial presenting sign in children is very rare. Antiganglioside antibodies are presumed to have an important role in the pathophysiology and some phenotypic correlations have been reported. Anti-GM2 antibody, unlike other antibodies, is far less detected in GBS. Here, we report a 7.5-year-old female, initially presenting with ataxia, an atypical presenting symptom in a child, is promptly diagnosed and treated successfully as GBS. Atypical history of urinary infection in our patient is an interesting aspect. The presence of isolated anti-GM2 IgM antibody and ataxia in a pediatric patient is rare. In this case report, we aim to describe an atypical initial presentation, with positive anti-GM2 antibodies, as well as review literature on isolated anti-GM2 positive pediatric GBS patients.


Comparative Genome Analysis of Old World and New World TYLCV Reveals a Biasness toward Highly Variable Amino Acids in Coat Protein.
Begomoviruses, belonging to the family Geminiviridae and the genus Begomovirus, are DNA viruses that are transmitted by whitefly Bemisia tabaci (Gennadius) in a circulative persistent manner. They can easily adapt to new hosts and environments due to their wide host range and global distribution. However, the factors responsible for their adaptability and coevolutionary forces are yet to be explored. Among BGVs, TYLCV exhibits the broadest range of hosts. In this study, we have identified variable and coevolving amino acid sites in the proteins of Tomato yellow leaf curl virus (TYLCV) isolates from Old World (African, Indian, Japanese, and Oceania) and New World (Central and Southern America). We focused on mutations in the coat protein (CP), as it is highly variable and interacts with both vectors and host plants. Our observations indicate that some mutations were accumulating in Old World TYLCV isolates due to positive selection, with the S149N mutation being of particular interest. This mutation is associated with TYLCV isolates that have spread in Europe and Asia and is dominant in 78% of TYLCV isolates. On the other hand, the S149T mutation is restricted to isolates from Saudi Arabia. We further explored the implications of these amino acid changes through structural modeling. The results presented in this study suggest that certain hypervariable regions in the genome of TYLCV are conserved and may be important for adapting to different host environments. These regions could contribute to the mutational robustness of the virus, allowing it to persist in different host populations.


Actomyosin Activity and Piezo1 Activity Synergistically Drive Urinary System Fibroblast Activation.
Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT). The findings reveal that the two distinct signaling pathways are integrated to convert mechanical stiffness signals into biochemical signals during bladder-specific FMT. Moreover, it is demonstrated that the crosstalk between myosin II and Piezo1 sensing mechanisms synergistically establishes a sustained feed-forward loop that contributes to chromatin remodeling, induces the expression of downstream target genes, and ultimately exacerbates FMT, in which the intracellular force activates Piezo1 by PI3K/PIP3 pathway-mediated membrane tension and the Piezo1-regulated calcium influx enhances intracellular force by the classical FAK/RhoA/ROCK pathway. Finally, the multifunctional Piezo1 in the complex feedback circuit of FMT drives to further identify that targeting Piezo1 as a therapeutic option for ameliorating bladder fibrosis and dysfunction.


Triptolide suppresses the proliferation and induces the apoptosis of nasopharyngeal carcinoma cells via the PI3K/Akt pathway.
Nasopharyngeal carcinoma (NPC) is an endothelium-associated malignancy that is heavily influenced by Epstein Barr virus infection. Triptolide, extracted from Tripterygium wilfordii, has been proven to possess anti-inflammatory, immunosuppressive and anti-cancerous activity. Although the effect of triptolide on numerous cancer cell types has been outlined, its effect in NPC remained unclear. The present study investigated the effects and underlying mechanisms of triptolide in C666-1 and NP69 cells. It was revealed that triptolide significantly inhibited proliferation and induced apoptosis in C666-1 cells. Increased levels of cleaved-caspase-3 and apoptosis regulator BAX, decreased expression of apoptosis regulator Bcl-2, and reduced phosphorylation of RAC-α serine/threonine-protein kinase (Akt), were responsible for this induction of apoptosis. Notably, pretreating C666-1 cells with the phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002 suggested that with increasing concentrations of LY294002, triptolide exhibited decreasing ability to suppress proliferation and induce apoptosis in these cells. In conclusion, the results demonstrated that triptolide suppressed the proliferation and induced the apoptosis of C666-1 cells in a PI3K/Akt-dependent manner and therefore, may serve as a promising therapeutic candidate for NPC.


Magnetic nanoparticle assembly on surfaces using click chemistry.
Controlled assembly of ferromagnetic nanoparticles on surfaces is of crucial importance for a range of spintronic and data storage applications. Here, we present a novel method for assembling monolayers of ferromagnetic FePt nanoparticles on silicon oxide substrates using "click chemistry". Reaction of alkyne-functionalized FePt nanoparticles with azide-terminated self-assembled monolayers (SAMs), on silicon oxide, leads to the irreversible attachment of magnetic nanoparticles to the surface via triazole linkers. Based on this covalent interaction, well-packed monolayers of FePt nanoparticles were prepared and nanoparticle patterns are generated on surfaces via microcontact printing (μCP).


Cyclic Stretch Promotes Proliferation and Contraction of Human Bladder Smooth Muscle Cells by Cajal-Mediated c-kit Expression in Interstitial Cells.
BACKGROUND The present study was performed to assess the effect of mechanical stretch on the proliferation and contractile function of hBSMCs. MATERIAL AND METHODS hBSMCs and ICCs were seeded at 8×104 cells/well in 6-well silicone elastomer-bottomed culture plates coated with type I collagen, and grown to 80% confluence in DMEM/10% FBS and a 5% CO₂ humidified atmosphere at 37°C. Cells of hBSMCs and hBSMCs/ICCs of co-culture were then subjected to continuous cycles of stretch-relaxation using a computer-driven, stretch-inducing device. The treated concentration of imatinib was 10 μM. Mechanisms underlying observed hBSMCs contraction were examined using Western blotting and RT-PCR. The 0.1 μM carbachol was separately added to the experimental groups, and 300 s was recorded by laser scanning confocal microscope. RESULTS We found that mechanical stretch increased contraction and proliferation of hBSMCs. Calcium ion activity increased significantly after mechanical stretch. The number of hBSMCs was significantly increased after the combination mechanical stretch with ICCs treatment. After combination mechanical stretch with hBSMCs/ICCs treatment, the mRNA and protein level of M2, M3, and c-kit were significantly increased. After combination of mechanical stretch with no imatinib treatment, the proliferation of hBSMCs was higher than others, and the mRNA and protein level of M2 and M3 were significantly increased. CONCLUSIONS We revealed that ICCs could promote hBSMC proliferation and contraction, and cyclic stretch could promote acetylcholine receptor M2 and M3 caused by c-kit in the ICCs, which promoted the contraction of hBSMCs.


Assessment of the effects of frequent ventricular extrasystoles on the left ventricle using speckle tracking echocardiography in apparently normal hearts.
Impairment in left ventricular (LV) function due to excessive ventricular extrasystoles (VESs) occurs during long-time follow-up. Speckle tracking echocardiography (STE) has been shown to be superior to conventional methods for evaluating cardiac functions. We aimed to use STE for early detection of LV dysfunction in patients with apparently normal hearts who have frequent VESs. Fifty-five patients with frequent VESs were identified according to the Lown classification (Grade 2; unifocal more than 30 times in 1 h). Subjects aged 22-60 years with frequent VESs that had been detected for at least 1 year were included in the study according to the inclusion criteria. Forty-five subjects with similar demographic characteristics, but without VESs, were included as the control group. All participants were evaluated by STE. Fifty-five patients with frequent VESs (mean age 47 years, range 22-60 years; 42.2% male) and 45 control subjects (mean age 46 years, range 22-60 years; 37.8% male) were enrolled in the study. Global LV longitudinal strain (GLS) was decreased in patients with frequent VESs (-18.41±3.37 and -21.82±2.43; p<0.001). In addition, global LV circumferential strain was decreased in patients with frequent VESs (-16.83±6.06, -20.51±6.02; p<0.001). The frequency and exposure time of VESs were negatively correlated with GLS (r=-0.398, p<0.001; r=-0.191, p=0.001, respectively). STE revealed that LV functions were decreased in patients with VESs. This deterioration increased with the frequency and exposure time of VESs. Impairment of LV function due to excessive VESs occurs during long-time follow-up. STE may be used for early detection of LV dysfunction.


Quantitative proteomic and phosphoproteomic analysis of chicken skeletal muscle during embryonic development.
Skeletal muscle also plays a vital role in regulating the movement energy storage and health of metabolism. In order to investigate the expression profile of protein and phosphor-proteins in chicken skeletal muscle during embryonic development, we performed phosphor-proteomics analysis by label-free and TiO2 enrichment strategy in chicken leg muscle tissues of at embryonic age embryo day 7(E7), E12, E17 and 3-day post-hatch (D3). The study led to the identification of 4332 proteins in the proteome and 1043 phosphorylation modification sites in the phosphorylated proteome, corresponding to 718 proteins (FC ≥ 2 or FC ≤ 0.5 and p < 0.05). The DEP-associated biological processes were involved in Focal adhesion, Glycolysis/gluconeogenesis, Arginine and proline metabolism by KEGG analysis. PPI analyses revealed that these DEPs TNNC1, TNNC2, TNNT2, TNNT3 and phosphorylated DEPs MYLPF interacted with involved pathways. Integrative analysis of proteome and phosphoproteome data found 324 common proteins, corresponding to 521 modification sites and Focal adhesion was the only pathway significantly enriched. These results provide a basis for further understanding the proteome and phosphoproteome and their regulatory biochemical pathways during the development of embryonic chicken skeletal muscle.


Identification of amino acid residues modified by two ATP analogs in Bacillus subtilis glutamine synthetase.
Bacillus subtilis glutamine synthetase was modified by two ATP analogs, 5'-p-fluorosulfonylbenzoyladenosine (FSBA) and 8-azidoadenosine 5'-triphosphate (8-N3-ATP), each one containing either Mg2+ or Mn2+. The FSBA labeled peptide was monitored by measuring the characteristic absorbance of the 4-carboxybenzenesulfonyl (CBS) part at 243 nm. The 8-N3ATP photolabeled peptide could also be monitored by measuring its absorption at 310 nm. A single CBS-labeled tryptic peptide was obtained, spanning residues 89-91 from the N-terminal of the subunit polypeptide chain, and sequence analysis by Edman degradation revealed that CBS-arginine was at position 91. The amino acids photolabeled by 8-N3ATP at the ATP-binding site in B. subtilis GS were His-186, His-187, and Trp-424. These results suggested that these four amino acids constitute an ATP-binding active site located at the interface between two subunits. The region surrounding Trp-424, which varies among different prokaryotic enzymes, was considered to be involved in a catalytic or regulatory role in B. subtilis GS. Since the same amino acids were labeled when B. subtilis GS was modified with FSBA or 8-N3ATP in the presence of Mn2+ or Mg2+, no conformational difference between B. subtilis GS binding Mn(2+)-ATP and that binding Mg(2+)-ATP was detected by affinity labeling with ATP analogs.


Malondialdehyde formation as an indicator of prostaglandin production by human platelets.
The formation of malondialdehyde, a metabolite of prostaglandin endoperoxides, has been studied in platelet-rich plasma. Small amounts were produced in response to ADP, epinephrine, or collagen and larger amounts in response to thrombin. Arachidonic acid induced platelets to produce large amounts of malondialdehyde. Malondialdehyde formation by platelets was prevented by aspirin or indomethacin. The measurement of malondialdehyde in platelet-rich plasma may be used as an indicator of platelet prostaglandin synthesis, and is simpler than the measurement of prostaglandins.


Evidence of long term benefit of morbidity reduction due to praziquantel treatment against schistosoma mansoni in kigungu fishing village in entebbe, Uganda.
Praziquantel (PZQ) is efficacious against Schistosoma mansoni. This was prospective cohort study. This study was carried out at Kigungu fishing village, Entebbe, Uganda. The goal of the study was to establish cost effective regiment for mass drug administration (MDA) of Praziquentel in the morbidity reduction of S.mansoni infection. In January 2004, nine hundred and forty five (945) participants were registered in this study. Our analysis was based on examining microscopically three slides prepared from each of 945 stool specimens delivered by each of the participant using modified Kato/Katz method. These included male and female, children and adults living in Kigungu fishing village in Entebbe Uganda. In total 901, cohorts were re-examined for infections clearance six months later in July 2004 and 18 months later in June 2005, 625 cohorts were again re-evaluated for S.mansoni infections after the baseline study. At baseline, (448) of 945 (47.5%) cohorts were S. mansoni positive. All these participants were treatment with a single oral dose of praziquantel at 40mg/kg. At the same time, 495 (52.5%) were S. mansoni negative. Of the 625 (66.3%) cohorts who came back for final review, 80 (12.8%) were still positive for S. mansoni while 210 (33.6%) remained negative after the base line treatment with praziquantel. On the other hand 103 (16.3%) of cohorts who were initially negative at the base line became S.mansoni positive after 18 months and 213(34.1%) remained negative for S.mansoni. The force of re-infection after six months was significant {(P=0.0001), (OR 0.47) CI at 95% (0.31-0.71)}. Nevertheless the force of reinfection was not significant after 18 months {(P=0.766), (OR 0.95) CI at 95% (0.68-1.34)}.The geometric mean eggs excretion of the 80 cohorts who were S.mansoni positive at 18 months was 151.967.This did not reach the geometric mean egg excreted by the same cohorts at baseline which was 285.05. The egg excretion was reduced by 46.8%. Similarly there was marked decrease in clinical symptoms amongst the cohorts. Our study suggests evidence of long-term benefit of praziquantel in Kigungu and that a yearly administration of praziquantel to the community could be a regiment for mass drug administration (MAD) for this community to control schistosomiasis morbidity.


Lung cancer mortality in relation to age, duration of smoking, and daily cigarette consumption: results from Cancer Prevention Study II.
The magnitude of the effect of smoking duration on lung cancer mortality relative to that of intensity (cigarettes/day) has practical implications for both tobacco control policy and research. This issue was addressed by R. Doll and R. Peto (J. Epidemiol. Commun. Health, 32: 303-313, 1978) in their historic analysis of one of the few large cohort studies in which intensity and duration were estimated separately. Their findings have been interpreted to mean that smoking duration is much more important than smoking intensity in causing lung cancer. The separate contributions of smoking duration and intensity to lung cancer risk have not been evaluated in other large prospective studies. We studied participants in the Cancer Prevention Study II, followed from 1982 through 1988. After restricting to people 40-79 years old who smoked < or =40 cigarettes per day at enrollment, we fit Poisson models for four age groups and evaluated lung cancer mortality (M) in relation to smoking duration (D) and intensity (I) on a double-log scale, as suggested by the Armitage-Doll multistage carcinogenesis model. The age-specific mortality estimates for men (M(m)) and for women (M(w)), when transformed to the original scale, were: ages 40-49: M(m) = e(-17.9) x D(1.9) x I(0.95), M(w) = e(-20.2) x D(2.8) x I(0.96); ages 50-59: M(m) = e(-17.4) x D(2.6) x I(0.52), M(m) = e(-17.2) x D(2.2) x I(0.75); ages 60-69: M(m) = e(-15.7) x D(2.4) x I(0.37), M(m) = e(-14.1) x D(1.5) x I(0.78); ages 70-79: M(m) = e(-13.0) x D(1.8) x I(0.39), M(m) = e(-13.2) x D(1.3) x I(0.95). Our study confirms that years of cigarette smoking is far more important than the number of cigarettes smoked per day in predicting lung cancer risk in United States men, regardless of age, and provides new evidence that a qualitatively similar pattern holds for women. The results support measures to prevent the uptake of smoking by adolescents and increase cessation. We discuss reasons why the associations we observe are lower than those reported by R. Doll and R. Peto (J. Epidemiol. Commun. Health, 32: 303-313, 1978).


Integrated density of states algorithm for one-dimensional randomly layered optical media.
Anderson localization simulations in one-dimensional disordered optical systems usually focus on the localization length or its inverse, but the calculation of the density of states has appeared less frequently for such models. In this paper a technique originally used to calculate the integrated density of states for one-dimensional disordered crystals supporting electron propagation is modified for use with randomly layered optical media. The density of states is then readily available via differentiation. The algorithm is demonstrated on one-dimensional quarter-wave stack and non-quarter-wave stack models with layer thicknesses disordered.


Achalasia Subtype Differences Based on Respiratory Symptoms and Radiographic Findings.
Three subtypes of achalasia have been defined using esophageal manometry. Several studies have reported that symptoms are experienced differently among men and women, regardless of subtype. All subtypes could have some impact on the appearance of respiratory symptoms and lung complications due to compression of the trachea or aspiration of undigested food. The aim of this research was to analyze the differences in respiratory symptoms and radiographic presentation of lung pathology depending on the diameter and achalasia types. One or more respiratory symptoms were reported in 48% of 114 patients, and all of them had two or more gastrointestinal symptoms. The symptom score (SS) is statistically significant for the prediction of subtype 1 (area under the curve = 0.318; p < 0.001, cut-off score of 6.5 had 95.2% sensitivity) and subtype 2 (area under the curve = 0.626; p = 0.020, cut-off score of 7.5 had 93.1% sensitivity). The most common type was subtype 2 (50.8%), and although only 14 patients had subtype 3, they had the largest esophageal diameter (mean 5.8 cm). The difference in esophageal diameter was significant between subtype 1 and 3 (p = 0.011), subtype 2 and subtype 3 (p = 0.011). Nine patients (6%) had mega-esophagus (four patients in type 1, three in type 2 and two in type 3). More than half of all patients (51.7%) had at least one parenchymal lung change on CT scan. Recurrent micro-aspirations led to changes in the structure of the airways and lung parenchyma such as ground glass (GGO) and nodular changes (12%) and fibrosis (14.5%), and they had higher esophageal diameters (p < 0.001). Patients with chronic lung CT changes had significantly higher esophageal diameter than with acute changes (p < 0.001). Awareness of the association of achalasia and lung disorders is important in early diagnosis and treatment. More than half (57.5%) of patients with achalasia had some clinical and/or structural pulmonary abnormalities. All three subtypes had similar respiratory symptoms, meaning they cannot be used to predict the subtype of achalasia; on the contrary, SS can predict the first two subtypes. A higher diameter of the esophagus is associated with chronic structural lung changes. Although unexpected, the pathological radiological findings and diameter were significantly different in subtype 3 patients, but those parameters cannot lead us to a specified subtype.


Role of sensory neuropeptides in PIV-3-infection-induced airway hyperresponsiveness in guinea pigs.
Viral respiratory tract infections are known to induce transient airway hyper-responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by nasal route. 16 animals served as untreated controls. Viral infection was proven by histological changes and by demonstration of viral antigen using immunohistochemical techniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheotomized guinea pigs. The ACH concentration which produced an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8 noninfected control animals were pretreated with capsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus inoculation. Measurements of airway responsiveness to ACH were performed 4 days after virus inoculation. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supermatant. PIV-3 infection increased airway responsiveness to ACH compared to noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn 0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected animals, airway hyperresponsiveness was completely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion with capsaicin completely prevented the increase in airway constrictory response to ACH following virus infection, we conclude that neuropeptides are effectively involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.


Tuning Xanthan Viscosity by Directed Random Coil-to-Helix Transition.
Xanthan gum is a polysaccharide that is widely used as a thickening agent in numerous food, cosmetic, and technical applications. Therefore, the knowledge of the molecular interplay that builds up and stabilizes water-binding networks is crucial for the optimization of xanthan thickening performance. Using atomic force microscopy, rheometry, and inductively coupled plasma optical emission spectroscopy, we show a clear correlation between xanthan thickening properties and the ability to form characteristic secondary structures as well as the valence and amount of cations coordinated at the polysaccharide side chain. Based on these findings and the Debye-Hückel theory, we derive an ion-interaction model in which divalent cations mediate bridging of adjacent single polymer strands due to chelate-like coordination building stable secondary structures. We furthermore demonstrate in a cation exchange assay that xanthan secondary structures can be modified in a directed and reversible manner, which, in turn, alters its thickening properties.


[A model of lumbar disc degeneration on the early stage in rhesus monkey with minimally invasive technique].
To establish a novel model of lumbar disc degeneration on the early stage in the rhesus monkey using percutaneous needle puncture guided by CT. (1) Thirteen rhesus monkeys aged from 4 to 7 years, female 7 and male 6 were selected for establishing a model of the early stage of lumbar disc degeneration. (2)13 monkeys, 91 discs were divided into 3 groups: 64 discs from L1/2 to L5/6 were percutaneous punctured with a needle 20G as experimental group and 1 disc with a needle 15G as puncture control group and 26 discs were not be punctured from L6,7 to L7-S1 as control group. (3) Lumbar disc localization for needle puncture was guided by CT. All discs were examined by MRI, the HE, Masson's trichrome, Safranine-O and immunohistochemical staining of type II collagen before disc puncture and after puncture at 4, 8 and 12 weeks. MRI: (1) Experimental group: Pfirmann's Grade I was shown at postoperation 4, 8 and 12 weeks; (2) Puncture control group: Grade III was shown at postoperation 4 weeks and Grade IV at 8 weeks; (3) CONTROL GROUP: Grade I was shown at postoperation 4, 8 and 12 weeks. Histological examination: (1) In experimental group, there was no any change at postoperation 4 weeks, and the cell population of the nucleus was decreased at 8 weeks and more decreased at 12 weeks in HE. (2) There was no any change at postoperation 4 weeks, the clefts among the lamellae of the annulus fibrosus (AF) were shown at 8 weeks and more wider of the clefts of AF at 12 weeks in Masson's trichrome. (3) No any change was shown at postoperation 4 weeks, proteoglycan were progressively decreased at 8 and 12 weeks in Safranine-O. (4) No statistically significant difference in positive rate was observed at 4 and 8 weeks compared with control group in immunohistochemical staining of type II collagen. There was statistical difference at 12 weeks compared with control group (P<0.05). In puncture control group postoperation 8 weeks, the morphology of cell of nucleus pulposus was not clear in HE. The wider clefts of lamellae of the AF were shown in Masson's trichrome. The proteoglycan was obviously decreased in Safranine-O. Immunohistochemical staining collagen II synthesized was decreased. In normal control group, no any change was shown at 4, 8 and 12 weeks. The degeneration of lumbar intervertebral disc on the early stage could be induced by the percutaneous needle puncture (20G) to the annulus fibrosus. The assessment of disc degeneration on early stage is not shown on MRI and only confirmed by histological examination.


[Acute renal failure in patients with tumour lysis sindrome].
`Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al.), as well as solid tumours (renal, liver, lung, ovarian, etc.), can lead to acute or chronic renal failure.The most common clinical manifestation is acute renal failure within the tumour lysis syndrome (TLS). It is characterized by specific laboratory and clinical criteria in order to prove that kidney disorders result from cytolysis of tumour cells after chemotherapy regimen given, although on significantly fewer occasions it is likely to occur spontaneously or after radiotherapy. Essentially, failure is the disorder of functionally conserved kidney or of kidney with varying degrees of renal insufficiency, which render the kidney impaired and unable to effectively eliminate the end products of massive cytolysis and to correct the resulting disorders: hyperuricemia, hyperkalemia, hypocalcaemia, hyperphosphatemia, and others. The risk of TLS depends on tumour size, proliferative potential of malignant cells, renal function and the presence of accompanying diseases and disorders. Hydration providing adequate diuresis and administration of urinary suppressants (allopurinol, febuxostat) significantly reduce the risk of developing TLS. If prevention of renal impairment isn't possible, the treatment should be supplemented with hemodynamic monitoring and pharmacological support, with the possible application of recombinant urate-oxidase enzyme (rasburicase). Depending on the severity of azotemia and hydroelectrolytic disorders, application of some of the methods of renal replacement therapy may be considered.


Improving Adherence to Topical Medication in Patients with Glaucoma.
The glaucomas form a heterogenous group of conditions, which collectively account for one of the most common irreversible causes of blindness worldwide. The only treatment, for which there is evidence, to stop or slow glaucomatous disease progression is to lower intraocular pressure (IOP); this is most often initially achieved with topical medication. Adherence to anti-glaucoma therapy is known to be low even when compared with adherence to therapy for other chronic conditions. We performed a PubMed search to review evidence as to how adherence to and persistence with anti-glaucoma medications might be improved. Approaches to improving adherence include technological (such as using smart drop bottles or automated reminders) use of instillation aids, improving communication with patient education and improving tolerability of eye drop formulations. There is limited short-term evidence that automated reminders can be effective and, unfortunately, instillation aids have not proved to be efficacious with respect to improving adherence. A range of factors have been identified which affect adherence and persistence, although only a multi-faceted approach has proven evidence of efficacy, compared to improved patient education alone. There is now a wider range of available preservative-free eye drops, which have been shown to be non-inferior in achieving IOP control, with fewer side effects and improved short-term adherence. Further studies relating to adherence are warranted, particularly given the projected increase in glaucoma prevalence worldwide.


Production and characterization of three monoclonal antibodies to Candida albicans proteins.
Three monoclonal antibodies, designated A2C7, C2C7, and F19, were produced which recognize proteins from Candida albicans. All are of the immunoglobulin G1 heavy chain and kappa light chain class. A2C7 and C2C7 immunoprecipitated three proteins contained in a partially purified fraction (region A) of a mycelial cytoplasmic extract of C. albicans. The apparent molecular weights of these proteins are 120,000 (120K) to 135K, 44K to 52K, to 38K. Monoclonal antibody F19 was reactive with proteins of 42K, 43K, and 50K in immunoblotting experiments. F19 was also able to form a precipitin band in agarose gel with protein(s) contained in region A. Limited proteolytic digestion of the three proteins immunoprecipitated by A2C7 and C2C7 demonstrated that both monoclonal antibodies recognized the same three Candida proteins and that there exists a significant degree of relatedness in primary structure among the three proteins. Proteins with apparent molecular weights of 120K to 135K, 44K to 52K, and 35K to 38K that were immunoprecipitated by sera from two patients with invasive candidiasis and by the serum from a rabbit immunized against a 48K (44K to 52K) Candida protein were also analyzed by limited proteolysis. Patterns of peptide fragments generated by enzymatic digestion of these proteins showed that the proteins recognized by the monoclonal antibodies are the same proteins recognized by antibodies in the sera of patients during an invasive Candida infection and by antibodies in the serum of the immune rabbit.


Changes in EMG coherence between long and short thumb abductor muscles during human development.
In adults, motoneurone pools of synergistic muscles that act around a common joint share a common presynaptic drive. Common drive can be revealed by both time domain and frequency domain analysis of EMG signals. Analysis in the frequency domain reveals significant coherence in the range 1-45 Hz, with maximal coherence in low (1-12 Hz) and high (16-32 Hz) ranges. The high-frequency range depends on cortical drive to motoneurones and is coherent with cortical oscillations at approximately 20 Hz frequencies. It is of interest to know whether oscillatory drive to human motoneurone pools changes with development. In the present study we examined age-related changes in coherence between rectified surface EMG signals recorded from the short and long thumb abductor muscles during steady isometric contraction obtained while subjects abducted the thumb against a manipulandum. We analysed EMG data from 36 subjects aged between 4 and 14 years, and 11 adult subjects aged between 22 and 59 years. Using the techniques of pooled coherence analysis and the chi(2) difference of coherence test we demonstrate that between the ages of 7 and 9 years, and 12 and 14 years, there are marked increases in the prevalence and magnitude of coherence at frequencies between 11 and 45 Hz. The data from subjects aged 12-14 years were similar to those obtained from adult controls. The most significant differences between younger children and the older age groups were detected at frequencies close to 20 Hz. We believe that these are the first reported results demonstrating significant late maturational changes in the approximately 20 Hz common oscillatory drive to human motoneurone pools.


Providers of primary care to homeless women in Los Angeles County.
Little is known about the access barriers homeless women face at the sites where they are most likely to receive primary health care. To investigate this issue, we administered a mail survey to administrators and clinicians at clinic sites that were actual or potential providers of primary health care to homeless women in Los Angeles County in 1997. The response rate was 65%. Ninety percent of the homeless women seen by responding sites were seen at only 34% of those sites (designated as "major providers"). Deficiencies were identified in several structural and process characteristics that enhance access to and quality of care for homeless women, including clinician training in care for homeless persons; formal screening for homeless status and associated risk factors; and on-site provision of comprehensive health services, including mental health, substance abuse, reproductive health, and ancillary services. Some, but not all, deficiencies were less severe at major providers. Our results suggest that, although providers of care to homeless women share challenges faced by many safety net providers, there are several policy interventions that could improve access to and quality of care for homeless women.


Whole-blood aggregometry: are there any limits with regard to platelet counts?
Whole-blood aggregometry (WBA) is a promising tool to assess platelet function in its physiological environment. Dilution of whole blood in WBA disregards platelet concentrations that may impact the results, especially in the case of low platelet counts. In a blinded, prospective in vitro study, the influence of platelet concentrations on WBA was assessed. Aggregation studies were carried out using whole blood from 10 healthy volunteers adjusted to platelet concentrations of 150, 100, 75, 50 and 25/nl using a plasma-balanced crystalloid solution. Platelet aggregation was measured by a new near-side whole blood aggregometer, activated by adenosin-diphosphate, collagen and thrombin-receptor activating protein. Three different approaches were applied: P1: whole blood diluted by an isotonic saline solution before activation, P2: undiluted whole blood with the single and P3: with the twofold concentration of the stimulating agent. Aggregometry in diluted whole blood (P1) decreased significantly from a platelet concentration of 100/nl (P<0.01). In undiluted whole blood, aggregation declined significantly from concentrations of 75 and 50/nl for P2 and P3 (P<0.01). No correlation to platelet count occurred in the undiluted approaches until a platelet concentration of 75/nl, whereas correlation in the diluted test run was detected starting from 100/nl. This study demonstrates that WBA depends on the platelet count and sensitivity towards low platelet concentrations may be improved by abdication of further dilution and the use of undiluted whole blood.


Recent Trends in the Withdrawal of Life-Sustaining Treatment in Patients with Acute Cerebrovascular Disease : 2017-2021.
The Act on Life-Sustaining Treatment (LST) decisions for end-of-life patients has been effective since February 2018. An increasing number of patients and their families want to withhold or withdraw from LST when medical futility is expected. This study aimed to investigate the status of the Act on LST decisions for patients with acute cerebrovascular disease at a single hospital. Between January 2017 and December 2021, 227 patients with acute cerebrovascular diseases, including hemorrhagic stroke (n = 184) and ischemic stroke (n = 43), died at the hospital. The study period was divided into the periods before and after the Act. The duration of hospitalization decreased after the Act was implemented compared to before (15.9 ± 16.1 vs. 11.2 ± 18.6 days, P = 0.127). The rate of obtaining consent for the LST plan tended to increase after the Act (139/183 [76.0%] vs. 27/44 [61.4%], P = 0.077). Notably, none of the patients made an LST decision independently. Ventilator withdrawal was more frequently performed after the Act than before (52/183 [28.4%] vs. 0/44 [0%], P < 0.001). Conversely, the rate of organ donation decreased after the Act was implemented (5/183 [2.7%] vs. 6/44 [13.6%], P = 0.008). Refusal to undergo surgery was more common after the Act was implemented than before (87/149 [58.4%] vs. 15/41 [36.6%], P = 0.021) among the 190 patients who required surgery. After the Act on LST decisions was implemented, the rate of LST withdrawal increased in patients with acute cerebrovascular disease. However, the decision to withdraw LST was made by the patient's family rather than the patient themselves. After the execution of the Act, we also observed an increased rate of refusal to undergo surgery and a decreased rate of organ donation. The Act on LST decisions may reduce unnecessary treatments that prolong end-of-life processes without a curative effect. However, the widespread application of this law may also reduce beneficial treatments and contribute to a decline in organ donation.


The pharmaceutical industry and health reform: lessons from Europe.
Many countries in Europe, which have significant pharmaceutical industries, recently have embarked on reforms in the organization of their health care systems and methods of regulating the pharmaceutical market. This paper describes the different systems in major European countries and the changes taking place. Although it is too early to make final judgment on the impact of these changes, it is possible to predict some of the more likely outcomes. The organizational models and regulatory approaches in Europe offer a useful store of experience for those assessing the potential impact of reform proposals in the United States.


Sudden deafness with vertigo as a sole manifestation of anterior inferior cerebellar artery infarction.
Sudden deafness without associated neurological symptoms and signs is typically attributed to a viral inflammation of the labyrinth. Although sudden deafness occurs with anterior inferior cerebellar artery (AICA) infarction, the deafness is usually associated with other brainstem or cerebellum signs such as crossed sensory loss, lateral gaze palsy, facial palsy, Horner syndrome or cerebellar dysmetria. An 84-year-old woman suddenly developed right-sided tinnitus, hearing loss, vertigo and vomiting. Audiometry and electronystagmography documented absent auditory and vestibular function on the right side. T2-weighted and diffusion-weighted MRI showed a tiny infarct in the right lateral inferior pontine tegmentum. AICA occlusion can cause sudden deafness and vertigo without brainstem or cerebellar signs.


Infusing research into practice to promote quality care.
This article describes the Iowa Model of Research in Practice, a heuristic model used at the University of Iowa Hospitals and Clinics for infusing research into practice to improve the quality of care. The components of the model are presented with examples. The impact of the model on patient, staff, and fiscal outcomes is delineated.


From left to right all through the night: Characteristics of lying rest in zoo elephants.
Despite increased research during the past years, many characteristics of resting behavior in elephants are still unknown. For example, there is only limited data suggesting elephants express longer lying bouts and increased total nightly lying durations on soft substrates as compared to hard surfaces. Additionally, it has not been investigated how frequently elephants change body sides between lying bouts. Here we present these characteristics based on observations of nighttime lying behavior in 10 zoo elephants (5 African Loxodonta africana and 5 Asian Elephas maximus elephants) living in five different European facilities. We found that elephants housed on soft substrates have significantly increased total lying durations per night and longer average lying bouts. Furthermore, at 70%-85% of all bouts, a consistently higher frequency of side change between lying bouts occurred on soft substrates, leading to an overall equal laterality in resting behavior. Deviations from this pattern became evident in elephants living on nonsand flooring or/and in nondominant individuals of nonfamily groups, respectively. Based on our findings, we consider elephants to normally have several lying bouts per night with frequent side changes, given an appropriate substrate and healthy social environment. We encourage elephant-keeping facilities to monitor these characteristics in their elephants' nighttime behavior to determine opportunities for further improvements and detect alterations putatively indicating social or health problems in individual elephants at an early stage.


[Insulin resistance physiopathology].
AMONG THE BIOLOGICAL MEDIATORS OF INSULIN RESISTANCE: two compounds released by the adipocyte are found, such as free fatty acids and tumor necrosis factor-alpha. They are incriminated in the deleterious role of visceral adiposity on the metabolic parameters. INTRA-CELL CORTISOL: Attention is also focused on the potential implication of cortisol in the genesis of metabolic syndrome, because cortisol is a potent antagonist of the effect of insulin and its presence in excess enhances visceral obesity and insulin resistance. GENETIC ASPECTS: Although no major locus has yet been identified, recent findings of several mutations or polymorphisms in genes acting in different regulation systems (adiponectin, PPARgamma2) also provide an interesting insight into the pathogenesis of this syndrome. Moreover, there is growing epidemiological evidence that intra-uterine factors could induce a so-called programming of the individual that may, at least in part, account for the difficulties encountered by the classical genetic approach.


Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.
To describe the main findings of the Portland Diabetic Project, which elucidates the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes. In this ongoing 17-year prospective, nonrandomized, interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure, we investigated the effects of hyperglycemia, and its subsequent reduction by continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing blood glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of hospital stay (LOS), and hospital cost. In separate multivariate analyses, increasing hyperglycemia was found to be independently predictive of increasing mortality (P<0.0001), DSWI (P = 0.017), and LOS (P<0.002). Conversely, CII therapy, designed to achieve predetermined target blood glucose levels, independently reduced the risks of death and DSWI by 57% and 66%, respectively (P<0.0001 for both). Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%) and DSWI rates (0.8%) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portland CII Protocol. Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions, which, in turn, adversely alter mortality, LOS, and infection rates. The Portland CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation. CII protocols should be the standard care for glycometabolic control in all patients undergoing cardiac surgical procedures.


Silent, generic and plant kairomone sensitive odorant receptors from the Southern house mosquito.
The Southern house mosquito Culex quinquefasciatus has the largest repertoire of odorant receptors (ORs) of all mosquitoes and dipteran species whose genomes have been sequenced to date. Previously, we have identified and de-orphanized two ORs expressed in female antennae, CquiOR2 and CquiOR10, which are sensitive to oviposition attractants. In view of a new nomenclature for the Culex genome (VectorBase) we renamed these ORs as CquiOR21 (formerly CquiOR10) and CquiOR121 (CquiOR2). In addition, we selected ORs from six different phylogenetic groups for deorphanization. We cloned four of them by using cDNA from female antennae as a template. Attempts to clone CquiOR87 and CquiOR110 were unsuccessful either because they are pseudogenes or are not expressed in adult female antennae, the main olfactory tissue. By contrast, CquiOR1, CquiOR44, CquiOR73, and CquiOR161 were highly expressed in female antennae. To de-orphanize these ORs, we employed the Xenopus oocyte recording system. CquiORx-CquiOrco-expressed oocytes were challenged with a panel of 90 compounds, including known oviposition attractants, human and vertebrate host odorants, plant kairomones, and naturally occurring repellents. While CquiOR161 did not respond to any test compound in two different laboratories, CquiOR1 showed the features of a generic OR, with strong responses to 1-octen-3-ol and other ligands. CquiOR44 and CquiOR73 showed preference to plant-derived terpenoids and phenolic compounds, respectively. While fenchone was the best ligand for the former, 3,5-dimethylphenol elicited the strongest responses in the latter. The newly de-orphanized ORs may be involved in reception of plant kairomones and/or natural repellents.


Deep Learning with Microfluidics for Biotechnology.
Advances in high-throughput and multiplexed microfluidics have rewarded biotechnology researchers with vast amounts of data but not necessarily the ability to analyze complex data effectively. Over the past few years, deep artificial neural networks (ANNs) leveraging modern graphics processing units (GPUs) have enabled the rapid analysis of structured input data - sequences, images, videos - to predict complex outputs with unprecedented accuracy. While there have been early successes in flow cytometry, for example, the extensive potential of pairing microfluidics (to acquire data) and deep learning (to analyze data) to tackle biotechnology challenges remains largely untapped. Here we provide a roadmap to integrating deep learning and microfluidics in biotechnology laboratories that matches computational architectures to problem types, and provide an outlook on emerging opportunities.


Intelligent aging compensation scheme for oven-controlled crystal oscillators of batch production based on statistical distribution.
The aging of crystal oscillators is an inherent and irreversible process. There is often thought to be no need for special processing if the aging rate varies within an allowable range and the crystal oscillator works properly. However, the impact of aging can be aggravated over the course of lengthy operation. This paper proposes an intelligent compensation scheme for the aging of batch OCXOs (oven-controlled crystal oscillators) based on a statistical distribution, analyzes the aging data of OCXOs in the same batch, selects the typical samples, acquires the best aging prediction curves after assessing different models, and efficiently compensates for every qualified product for aging using this model. The results of experiments exhibited good compensation effects, with an improvement of one to two orders of magnitude in the aging indicators of the compensated OCXOs compared with the original without compensation.


Patient group directions: the legal and professional considerations.
Nurses have administered medicines 'according to protocol' for many years. Patient group directions have now been formalised. Nurses who supply and administer medications according to these directions must ensure that they have a clear understanding of their role. This paper seeks to clarify their use and to consider professional liability, accountability and development.


Do dissolving objects converge to a universal shape?
Surprisingly, macroscopic objects such as melting ice cubes and growing stalactites approach nonintuitive geometric ideals. Here we investigate the shape of dissolving cylinders in a large volume of water. The cylinders are oriented vertically and consist of amorphous glucose or poly(ethylene glycol). The dissolution causes density differences in the surrounding fluid, which induce gravity-driven convection downward along the object. The resulting concentration gradient shapes the cylinder according to fast dissolution at the tip and slow dissolution at the base. The contour of the object approaches a power law of the form z ∝ R(2), where z is the vertical distance from the tip and R is the corresponding radius. We suggest that this paraboloidal shape is the geometric attractor for the dissolution of noncrystalline objects in the presence of gravity.


Chromatin-dependent cooperativity between site-specific transcription factors in vivo.
Accessing binding sites in DNA wrapped around histones in condensed chromatin is an obstacle that transcription factors must overcome to regulate gene expression. Here we demonstrate cooperativity between two transcription factors, the glucocorticoid receptor (GR) and nuclear factor 1 (NF1) to bind the mouse mammary tumor virus promoter organized as regular chromatin in vivo. This cooperativity is not observed when the promoter is introduced transiently into cells. Using RNA interference to deplete NF1 protein levels in the cells, we confirmed that NF1 promotes binding of GR to the promoter. Furthermore, we observed a similar synergism between GR and NF1 binding on the endogenous 11beta-hydroxysteroid dehydrogenase promoter, also regulated by GR and NF1. Our results suggest that the chromatin architecture of the promoters does not permit strong association of GR in the absence of NF1. Therefore we propose that cooperativity among DNA binding factors in binding to their cognate recognition sites in chromatin may be an important feature in the regulation of gene expression.


A case report of successful removal of multiples sewing needles in the gastrointestinal tract and pancreas using intraoperative C-arm fluoroscopy.
Most ingested foreign bodies pass uneventfully through the digestive tract without any major disturbances. We reports a rare case of successful localization and surgical removal of needles in the gastrointestinal tract using C-arm fluoroscopy intraoperatively. A 46year old female, a non-hospitalized psychiatric patient, presented with acute abdominal pain. Imaging showed 16 needles all over the digestive tract. C arm fluoroscopy was used to successfully localize and remove all of the needles intraoperatively. One needle was withdrawn from the pancreas manually without pancreatic resection. It is estimated that up to 10-20% cases require endoscopic removal and 1% cases with the presence of obstruction or perforation necessitate surgical interventions [1-4] (Hsieh et al., 2005; Anderson and Dean, 2011; Cheng and Tam, 1999; Ricci et al., 2014). Migration to the pancreas extremely rare [5,6] (Toyonaga et al., 2001; Yasuda et al., 2010). Timely diagnosis can be difficult [7] (Tsui and Mossey, 1997). CT scan is a modality of choice to preoperatively locate the foreign body [8] (Takada et al., 2000). We herein successfully localized and removed 15 needles using C-arm fluoroscopy intraoperatively. It is extremely useful to accurately detect radiopaque foreign bodies. On the basic of findings on CT, treatment of choice such as endoscopic removal or surgical intervention may be attempted. CT scan is a modality of choice to preoperatively locate the foreign body. Sharp-pointed objects should be removed even if the patient is asymptomatic as the increased mortality and the risk of related complications. Intraoperative C-arm fluoroscopy is a feasible, cost-effective modality with real-time image to accurately detect multiple radiopaque objects especially when they are disseminating throughout the digestive tract.