Osteopathic care for low back pain and neck pain: A cost-utility analysis.
The aim was to examine the health and economic consequences of osteopathic care for low back pain and neck pain in addition to usual care compared to usual care alone. A decision tree model considering a one-year time horizon was applied. The analysis occurred from a health insurance perspective only considering direct medical costs. The health effects were expressed as quality-adjusted life years (QALYs). The main outcome was the incremental cost-effectiveness ratio (ICER). The uncertainty around key input parameters was addressed applying one-way and probabilistic sensitivity analyses (5000 simulations). For low back pain, osteopathy resulted in cost savings (€385.1 vs €501.8/patient) at improved QALYs (0.666 vs. 0.614) compared to usual care. For neck pain, osteopathy resulted in additional costs (€577.3 vs. €521.0) and improved QALYs (0.639 vs. 0.609) resulting in an ICER of €1,870/QALY. The one-way sensitivity analysis identified the hospitalization cost (back) and osteopathy cost (neck) as major cost drivers. The probabilistic sensitivity analysis resulted in an average net saving of €163 (95%CI-€260, -€49.1) and a QALY gain of 0.06 (95%CI -0.06, 0.17) for low back pain and an average additional cost of €55.1 (95%CI €20.9, €129) and improved QALY gain of 0.03 (95%CI-0.06, 0.12) for neck pain. Osteopathy was found to be a 'dominant' (low back pain) and cost-effective strategy (neck pain) compared to usual care. Further health economic evaluation studies considering a broader range of cost items and longer time horizon are required.


Endothelium-independent vasodilation effect of di- and tri-peptides in thoracic aorta of Sprague-Dawley rats.
The goal of this study was to elucidate the structure-activity relationship for vasodilating peptides and their underlying mechanism. In this study, we synthesized 62 di- and tri-peptides having aromatic amino acid residues (Tyr, Trp and Phe). Among them, only 4 peptides (HW, WH, WL and WV) evoked an apparent vasodilating effect in 50 mM KCl-contracted aortic rings in the descending order of WH>HW>WL>WV; WH showed the vasodilating activity with an EC50 of 3.4 mM. Within our experimental results, it seems likely that Trp residue at the N-terminal would play a role in eliciting vasodilating effect. No appearance of vasodilating effect for stereoisomers of WH with D-configuration revealed that the vessel would recognize the L-configuration of WH. The presence of angiotensin I-converting enzyme (ACE) inhibitor (50 nM enalaprilat) did not affect the WH-induced vasodilating effect, though WH showed a slight ACE inhibitory activity (IC50: 93 microM). The effect was also observed in the endothelium-denuded aortic rings. In contrast, WH provoked a significant displacement to the right in the vasodilating curve in the presence of 30 nM verapamil, while no shift was observed in the presence of 2.5 nM nifedipine. These results indicate that WH, a vasodilating di-peptide, would exert a vasodilation via the suppression of Ca2+ influx into KCl-induced depolarized aortic rings. The present study also suggests that the binding site of WH to the Ca2+ channel may be competitive to that of phenylalkylamine-type voltage-gated L-type Ca2+ channel blocker.


Nutritional status and the serum levels of Mg, Ca, Zn and Cu.
Serum Mg, Ca, Zn and Cu levels of 65 Indian children aged 5 months to 3 y 7 months, living in Bombay city, were estimated by atomic absorption spectrometry. Twenty-five well nourished controls exhibited the following serum levels: Mg 2.5 +/- 0.3 mg%, Ca 9.7 +/- 0.6 mg%, Zn 103.2 +/- 9.7 micrograms % and Cu 148.7 +/- 26 micrograms %. The remaining 40 patients were divided into four categories depending on the status of their nutrition; Group I was minimally undernourished, whereas Group IV was the worst effected. Group I (n = 6) had serum values of 2.5 +/- 0.2 mg% Mg, 8.9 +/- 0.6 mg% Ca, 85 +/- 18 micrograms % Zn and 108 +/- 25.8 micrograms % Cu. Group II (n = 20) levels were 2.2 +/- 0.3 mg% Mg, 8.3 +/- 0.9 mg% Ca, 82.6 +/- 16.5 micrograms %, Zn and 89.2 +/- 27.6 micrograms % Cu. Group III (n = 9) were 2.1 +/- 0.3 mg% Mg, 8.3 +/- 0.8 mg% Ca, 88.3 +/- 22.6 micrograms % Zn and 93 +/- 26.9 micrograms % Cu, whereas the most severely undernourished (Group IV) children had serum levels of 2.2 +/- 0.4 mg% Mg, 7.6 +/- 0.8 mg% Ca, 78.4 +/- 15.7 micrograms % Zn and 62.8 +/- 17.5 micrograms % Cu.


Skin absorption of inorganic lead (PbO) and the effect of skin cleansers.
The aim of this study was to investigate the percutaneous penetration of lead oxide (PbO) powder and the effect of rapid skin decontamination with two different detergents. Franz cells were used to study in vitro PbO skin penetration through human skin during a 24-hour period. The tests were performed without or with decontamination using either Ivory Liquid soap or a new experimental cleanser 30 minutes after the start of exposure. We confirm that PbO can pass through the skin with a median penetration of 2.9 ng/cm (25-75th percentiles 0.35-6). The cleaning procedure using Ivory Liquid soap significantly increased skin penetration with a median value of 23.6 ng/cm (25-75th percentiles 12-47.1; Mann-Whitney U test, P = 0.0002), whereas the new experimental cleanser only marginally increased penetration (7.1 ng/cm). Our results indicate that it is necessary to prevent skin contamination from occurring because a short contact can increase skin content and penetration even if quickly followed by washing. This study demonstrated that PbO powder can pass through the skin and that skin decontamination done after 30 minutes of exposure did not decrease skin absorption occurring over 24 hours and stresses the need to prevent skin contamination when using toxic substances.


Intrauterine administration of methyl cyanoacrylate as an outpatient method of permanent female sterilization.
Results are presented of multicenter studies on the intrauterine delivery of 0.6 ml methyl cyanoacrylate with the FEMCEPT device (BioNexus Inc., Raleigh, North Carolina) for the purpose of causing permanent obstruction of the fallopian tubes. The studies included 1279 women and were conducted under several different protocols that required either one or two methyl cyanoacrylate application procedures. Based on hysterosalpingograms obtained about 16 weeks after the last methyl cyanoacrylate application, one procedure resulted in a tubal closure rate of 71.4% and two procedures resulted in a tubal closure rate of 89.4%. Complications of the procedure were infrequent and none required surgical treatment. Cumulative pregnancy rates among women with hysterosalpingogram-demonstrated bilateral tubal closure were similar for the one- and two-application procedures that used nonradiopaque methyl cyanoacrylate and were significantly lower (p less than 0.05) compared with a single application of radiopaque methyl cyanoacrylate. The 3-year pregnancy rate for two applications of nonradiopaque methyl cyanoacrylate was 1.7 +/- 1.2 per 100 women.


Subclinical liver dysfunction in one-month-old infants with a low activity of vitamin K dependent coagulant factors assessed by normotest.
To clarify features of late vitamin K deficiency hemorrhagic disease in Japanese infants, seventeen of 1,687 infants screened by normotests were examined for signs and symptoms suggesting hepatobiliary diseases. Clinical observations disclosed findings suggesting hepatobiliary diseases in 7 of the 17 selected infants with normotest values of less than 40%, and 11 infants had abnormal results in one or more liver function tests. Taken together, 14 of the 17 infants had findings suggesting hepatobiliary diseases. Upon vitamin K supplementation normotest values improved in various degrees in all infants, whether or not they had signs or symptoms of hepatobiliary diseases. Late vitamin K deficiency hemorrhagic disease of infancy may be related to subclinical hepatobiliary diseases.


Reassessment of the normal fetal cisterna magna during gestation and an alternative approach to the definition of cisterna magna dilatation.
Cisterna magna (CM) measurement constitutes part of the sonographic assessment of the posterior fossa. CM enlargement (ECM) is defined as a measurement exceeding 10 mm, although it has previously been noted that the CM varies in size with gestation. Existing data do not appear to reflect observations regarding CM biometry within our population and this study was therefore undertaken in order to re-evaluate CM biometry. Data from 4,750 normal pregnancies between 15 and 32 weeks of gestation were collected and used to construct a reference range for the CM. Regression analysis was used to model CM across gestational age and thereby define the upper limits for normal CM measurements across gestation. The CM increases with gestation. These data suggest that a 10-mm cut-off underestimates ECM, notably in the gestational age period below 24 weeks, whilst overestimating isolated ECM beyond this. Differences in CM measurements between genders were confirmed (p < 0.0001). Defining ECM based upon a cut-off of 10 mm across all gestations may be inappropriate given the variation observed with gestational age. More accurate identification of fetuses with, in particular, isolated ECM may facilitate more precise evaluation of the clinical significance of this finding.


Palmoplantar keratoderma and oral leucoplakia with cutaneous horn of the lips.
The inherited palmoplantar keratodermas (PPK) may be associated with a wide variety of other ectodermal abnormalities. The coexistence of PPK and leucoplakia may indicate the increased risk of oesophageal carcinoma in adult life. Cutaneous horn may develop over benign, precancerous, as well as malignant lesions, and frequently may be associated with actinic keratoses and Bowen's disease. On the other hand, the relationship of cutaneous horn and leucoplakia has been the subject of only a single case report. We present a case of PPK and diffuse oral leucokeratosis associated with relapsing cutaneous horn of the lips.


Maternal obesity, gestational diabetes, breastfeeding and childhood overweight at age 2 years.
Maternal obesity, excessive gestational weight gain (EGWG), gestational diabetes mellitus (GDM) and breastfeeding are four important factors associated with childhood obesity. The objective of the study was to assess the interplay among these four factors and their independent contributions to childhood overweight in a cohort with standard clinical care. The cohort included 15 710 mother-offspring pairs delivered in 2011. Logistic regression was used to assess associations between maternal exposures and childhood overweight (body mass index >85th percentile) at age 2 years. Mothers with pre-pregnancy obesity or overweight were more likely to have EGWG, GDM and less likely to breastfeed ≥6 months. Mothers with GDM had 40-49% lower EGWG rates and similar breastfeeding rates compared with mothers without GDM. Analysis adjusted for exposures and covariates revealed an adjusted odds ratio (95% confidence interval) associated with childhood overweight at age 2 years of 2.34 (2.09-2.62), 1.50 (1.34-1.68), 1.23 (1.12-1.35), 0.95 (0.83-1.10) and 0.76 (0.69-0.83) for maternal obesity, overweight, EGWG, GDM and breastfeeding ≥6 months vs. <6 months, respectively. In this large clinical cohort, GDM was not associated with, but maternal pre-pregnancy obesity or overweight and EGWG were independently associated with an increased risk, and breastfeeding ≥6 months was associated with a decreased risk of childhood overweight at age 2 years.


Clinical advice from the bench.
This article discusses three aspects of family law: (1) a new approach to custody litigation currently in use in one family law court in New Mexico; (2) why some judges, lawyers, and family courts are slow to change the way family law cases are managed; and (3) how mental health professionals might change their interactions with the legal system to benefit both their professions and the people they serve.


RNA Crosslinking to Analyze the Mitochondrial RNA-Binding Proteome.
Even though the mammalian mitochondrial genome (mtDNA) is very small and only codes for 13 proteins, all being subunits of the oxidative phosphorylation system, it requires several hundred nuclear encoded proteins for its maintenance and expression. These include replication and transcription factors, approximately 80 mitoribosomal proteins and many proteins involved in the posttranscriptional modification, processing, and stability of mitochondrial RNAs. In recent years, many of these factors have been identified and functionally characterized, but the complete mtRNA-interacting proteome is not firmly established. Shotgun proteomics has been used successfully to define whole-cell polyadenylated RNA (poly(A)-RNA) interacting proteomes using the nucleotide analogue 4-thiouridine (4SU) combined with UV crosslinking, poly(A)-RNA isolation and mass spectrometry to identify all poly(A)-RNA bound proteins. Although in this case also a considerable number of mitochondrial proteins were identified, the method was not specifically directed at the mitochondrial poly(A)-RNA bound proteome. Here we describe a method for enrichment of the mitochondrial poly(A)-RNA bound proteome based on 4SU labeling and UV crosslinking. The method can be applied either for isolated mitochondria prior to UV crosslinking or for whole-cell crosslinking followed by mitochondrial isolation.


Ammonia stress decreased biomarker genes of acetoclastic methanogenesis and second peak of production rates during anaerobic digestion of swine manure.
Research shows that anaerobic digestion could acclimate to ammonia stress; however, the acclimation remained unaddressed. In this study, evolution of microbial community, functional gene, and pathway was linked with apparent kinetic and performance in unacclimated inoculum under ammonia stress, to deepen understanding of the acclimation. The second peak in production rate demonstrated crucial kinetic changes under ammonia stress. The methane loss was mainly protein in residual COD. Metagenomic showed initial inhibition in all methane metabolism pathways under ammonia stress, and recovery in acetate uptake was the key to ammonia acclimation. The acclimation was found in alternative pathway of Acetyl-CoA (CH3CO-S-CoA) synthesis from acetate, accompanying by syntrophic methanogenesis. Ammonia inhibited acetoclastic methanogenesis by competing CH3-CO-Pi with pta and formed speculative sediment CH3-CO-PO4[NH4]2. Biomarker of methanogenesis kinetic was suggested as mcr, hdr, and mch. The biomarker could indicate acclimation stages to ammonia, empowering anaerobic digestion by early warning of methane loss.


2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro.
Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.


Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia.
After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab-containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14-0.37; p < 0.0001) and 0.40 (0.22-0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16-0.27; p < 0.0001) and 0.29 (0.21-0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22-0.63; p = 0.0003) for PFS and 0.53 (0.27-1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.


Considerations for analysis of source monitoring data when investigating hallucinations in schizophrenia research.
Self/other (i.e., internal/external) source monitoring is one of the leading paradigms for the study of hallucinations in schizophrenia. The cognitive processes that underlie hallucinations are theorized to transform self-generated (internal) cognitive events into other-generated (external) cognitive events. These proposed cognitive operations also appear to play a role in producing analogous types of errors in self/other source monitoring, namely a memory bias whereby recalled material that was self-generated is misremembered as other-generated, referred to as an externalization bias. Externalization biases are more frequent in groups of hallucinating schizophrenia patients than in other groups. One source of measurement error that is inherent in the study of the externalization bias is that, even for never-previously viewed items, there is a tendency to guess an external source under conditions of uncertainty. If such guessing takes place in response to self-generated but forgotten items, these guesses will be summed along with true externalization biases in the frequency count of externalizations, producing measurement error. Multinomial modeling is a statistical technique that has been used to estimate the influence of external-source guessing in order to separate it from true externalization bias estimates. However, a number of challenges related to model choice and model validation are involved, and these challenges may render multinomial modeling impractical. We instead recommend analysis of covariance (ANCOVA), or difference score methodology, as an appropriate method for partialling external-source guessing rates (external-source false positives) out of externalization bias rates.


Retroperitoneal laparoscopic hepatectomy of recurrent hepatocellular carcinoma: case report and literature review.
Almost all liver tumours can be removed laparoscopically, but some difficult tumour locations complicate laparoscopic surgery. Recurrent liver tumours often pose great difficulties to laparoscopic surgery due to adhesions caused by previous operations. Referring to laparoscopic adrenalectomy, a retroperitoneal approach is proposed to remove liver tumours near the adrenal gland, which will provide a new method for liver surgery. Our case involves a patient with recurrent hepatocellular carcinoma (HCC) whose last operation was laparoscopic hepatectomy in our department, with a recurrence of HCC 2 years after the first surgery. In this case, based on preoperative CT and MRI, through a retroperitoneal approach, combined with intraoperative ultrasound (IOUS) localization and indocyanine green (ICG) fluorescence navigation, laparoscopic hepatectomy was successfully performed to precisely resect recurrent hepatocellular carcinoma in segment VII. The patient was discharged on the third day after the operation. The AFP decreased to normal levels on the 28th postoperative day. Retroperitoneal hepatectomy has the advantages of less trauma, shorter operation times, fewer complications and faster recovery for hepatic tumours near the adrenal gland. Accurate localization of tumours is needed to ensure accurate resection; therefore, IOUS and ICG fluorescence are very important. Liver parenchyma was severed strictly according to fluorescent labelling during hepatectomy, which prevented the deviation of liver parenchyma from the plane and ensured that the margin of hepatectomy was tumour-free. In order to ensure a radical resection of the tumour, it may be necessary to enter the abdominal cavity.


Effects of insulin and insulin-like growth factors on neurofilament mRNA and tubulin mRNA content in human neuroblastoma SH-SY5Y cells.
Insulin-like growth factors (IGFs) are implicated in the development of the vertebrate neural circuitry, and increase neurite growth in vitro and in vivo. The construction of the cytoskeleton is necessary for growth of axons and dendrites, and the neurofilament (NF) 68 kDa and 170 kDa proteins assemble to help form major fibrillar elements of the neurite cytoskeleton. We report that physiological concentrations of insulin, IGF-I or IGF-II increased the contents of 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs, relative to total RNA, in cultured human neuroblastoma SH-SY5Y cells. In contrast, the relative contents of histone 3.3 mRNA, and poly(A)+ RNA were not increased. Ligand concentrations which increased NF mRNAs were very similar to those which increased neurite outgrowth. Although each gene was evidently independently regulated, the 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs were nevertheless all transiently elevated over approximately the same time interval in response to insulin. These data, when considered together with studies by others with nerve growth factor, show that the 68 kDa and 170 kDa NF mRNAs are elevated in a biochemical pathway activated in common during neurite outgrowth directed by insulin, IGF-I, IGF-II, and nerve growth factor.


Ultracytochemical study of lytic complex insertion in the glycocalyx of red cells during immune hemolysis mediated by complement.
Ruthenium red (RR), a cationic dye and an ultrastructural tracer of cell membrane permeability, was used on sheep red blood cells after lysis produced by a specific antibody and guinea pig complement. In addition to the opacification of the glycocalyx, RR stained structures related to lytic complexes, which appeared as rod-like structures with variable dimensions (generally 45 nm in width, 75 nm in height) inserted in the glycocalyx of red cells. They extended across the external layer of the trilaminar plasma membrane without reaching the internal layer or the cytoplasm. RR staining visualized the internal configuration of the lytic complexes and revealed small channels measuring 10 nm in diameter localized within the complexes. These lytic complexes are thought to correspond to membrane attack complex of complement. To the best of our knowledge, this is the first report of ultrastructural positive staining of lytic complexes in thin sections, allowing visualization of their internal configuration and their insertion in the plasma membrane glycocalyx.


[Comparative characterization of mesenchymal bone marrow stromal cells at early and late stages of culturing].
The mesenchymal stromal cell is a multipotent precursor of osteoblasts, adipocytes, and some other cell types. In this study, a comparative analysis of cultured mesenchymal stromal cells from the rat bone marrow at the early and late stages of subculturing has been performed using molecular genetic and cytological methods. The culture has undergone 11 passages during 140 days. Upon long-term culturing, the mesenchymal stromal cells have proved to lose their potential for adipogenic differentiation but preserve the potential for osteogenesis. Morphological characters typical of osteogenic differentiation can be observed at the earlier stages of culturing (passages 1-4) but disappear at later stages (passages 9-11), despite mineralization of the extracellular matrix and the expression of osteogenic differentiation markers. A comparative analysis of the proliferation potential of stromal cells has shown that differences in the period of cell population doubling at the early and later stages of culturing are insignificant. An almost complete arrest of cell growth has been observed in the middle of the culture period (passages 5 and 6).


Combined modality therapy in Stage III and Stage IIIE diffuse large cell lymphomas.
Combined modality therapy consisting of CHOP-Bleo (cyclophosphamide, Adriamycin [doxorubicin], vincristine (Oncovin), prednisone, and bleomycin) and limited-field radiotherapy was given to 47 patients with Stage III and IIIE diffuse large cell lymphomas. Overall 5-year survival and disease-free survival figures are 64% and 53%, respectively. Twenty-nine patients achieved and maintained a complete remission during treatment; 92% of these patients are alive at 5 years, and 87% are disease-free. Prognostic factors were assessed for the entire group. Age, "B" symptoms, extranodal involvement, and extensive abdominal involvement had little effect on survival. However, the presence of mediastinal involvement and extensive abdominal involvement was associated with a poor response rate and survival.


Reflectance confocal microscopy in the diagnosis of vesicobullous disorders: case series with pathologic and cytologic correlation and literature review.
Vesicobullous disorders are characterized by intraepidermal or subepidermal blistering resulting from different pathogenetic mechanisms. The diagnosis is generally based on clinical examination and semi-invasive/invasive procedures such as cytology and histopathology. In vivo reflectance confocal microscopy (RCM) is a non-invasive technique for real-time, en face imaging of the epidermis and upper dermis with high resolution close to conventional histopathology. To evaluate RCM features of different vesicobullous diseases and correlate with cytologic and histopathologic examination. Ten patients (6M/4F, age range: 9-81 years) affected by blistering diseases, such as herpes simplex, herpes zoster, Kaposi's varicelliform eruption, pemphigus vulgaris, Hailey-Hailey disease, bullous pemphigoid, and porphyria cutanea tarda were evaluated using a handheld RCM device. In our study, a clear correlation between RCM and Tzanck's test and/or histopathology was observed. RCM allowed in all cases an easy identification of the blister spaces and of the split levels, and in some cases specific features were detected, such as giant keratinocytes in herpes infections and acantholytic cells in pemphigus vulgaris and Hailey-Hailey disease. Reflectance confocal microscopy may support the clinical diagnosis of vesicobullous disorders and indicate to the physician the appropriate patient management and/or the need for further investigation.


Women's nutritional status, iron consumption and weight gain during pregnancy in relation to neonatal weight and length in West Java, Indonesia.
Pregnant and non-pregnant women in Indramayu, West Java were examined for nutritional status, using anthropometric indicators. For the pregnant women, longitudinal data on nutritional status, iron consumption and weight gain were examined in relation to neonatal weight and length. Comparing the non-pregnant women's average nutritional status with reference tables for height, weight and MUAC, they placed at the 25th percentile or less on all indicators. Using original formulae to estimate pre-pregnancy weight and pregnancy weight gain, the study showed that 18% of pregnant women had a pre-pregnancy weight of under 40 kg and the average pregnancy weight gain was under 9 kg. Comparing estimated pregnancy weight gain with the amount of weight gain needed to compensate for generally low pre-pregnancy weight, only about 9% of women gained adequately. In multiple regression models that controlled for other maternal and neonatal factors, iron consumption during pregnancy was a significant predictor of full-term (37 weeks or more) neonatal weight (P = 0.01) and length (P = 0.01). Consumption of one or more tablets (200 mg ferrous sulfate and 0.25 mg folic acid) per week by women during pregnancy was associated with increased neonatal weight (by 172 g on average) and length (by 1 cm on average). Adequate weight gain during pregnancy and maternal height also contributed to the specification of the neonatal weight model (P = 0.07 for both). In the neonatal length model, maternal height was also nearly significant (P = 0.03). The same models did not explain the variability in neonatal weight and length in the pre-term group (< 37 weeks gestation).


Inhibition of oxidative stress induced-cytotoxicity by coptisine in V79-4 Chinese hamster lung fibroblasts through the induction of Nrf-2 mediated HO-1 expression.
Coptisine is a natural alkaloid compound and is known to have multiple beneficial effects including antioxidant activity. However, whether it can protect lung fibroblasts from oxidative damage has not been studied yet. To investigate the potential inhibitory effect of coptisine against oxidative stress in V79-4 lung fibroblast cells. V79-4 cells were treated with H2O2 (1 mM) in the presence or absence of coptisine (50 µg/ml), N-acetyl cysteine (NAC, 10 mM) or zinc protoporphyrin IX (ZnPP, 10 µM) for the indicated times. The alleviating effects of coptisine on cytotoxicity, cell cycle arrest, apoptosis, reactive oxygen species (ROS) production, DNA damage, mitochondrial dynamics, and inhibition of ATP production against H2O2 were investigated. Western blot analysis was used to analyze the expression levels of specific proteins. Coptisine inhibited H2O2-induced cytotoxicity and DNA damage by blocking abnormal ROS generation. H2O2 treatment caused cell cycle arrest at the G2/M phase accompanied by increased expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 and decreased expression of cyclin B1 and cyclin A. However, these effects were attenuated in the presence of coptisine or NAC. Coptisine also prevented apoptosis by decreasing the rate of Bax/Bcl-2 expression in H2O2-stimulated cells and suppressing the loss of mitochondrial membrane potential and the cytosolic release of cytochrome c. In addition, the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was markedly promoted by coptisine in the presence of H2O2. However, zinc protoporphyrin IX, a potent inhibitor of HO-1, attenuated the ROS scavenging and anti-apoptotic effects of coptisine. Based on current data, we suggest that coptisine can be used as a potential treatment for oxidative stress-related lung disease.


Quality and Content of Online Patient Resources for Celiac Disease.
Patient-directed information on celiac disease has been reported to be of variable quality. We assessed the quantity and quality of information on blogs and Web sites intended to inform the layperson of celiac disease information. We performed a cross-sectional study analyzing celiac disease blogs and Web sites intended for the layperson. We searched from 20 cities, resulting in 55 Web sites. These sites were analyzed for 38 criteria that considered relevant clinical information for people with celiac disease. Claims were classified as true, false, or not proven. The readability level of each Web site was determined. The 55 Web sites were categorized as national organizations, personal blogs, recipe-based blogs, or commercial/marketing Web sites. Only 40% of Web sites contained more than 50% of criteria. Of 212 claims assessed, 97% were found to be accurate. National organizations included the most criteria, followed by recipe-based blogs, then personal blogs, and lastly commercial/marketing Web sites. Additionally, national organizations had the highest proportion of accurate claims, followed by personal blogs, then commercial/marketing Web sites, and recipe-based blogs with the most inaccurate information. The average readability level of overall was 9.7, above the recommended readability level for patient education materials. A significant number of online claims regarding celiac disease were true, but the majority of patient-facing Web sites are missing large amounts of relevant information. This warrants efforts to improve the quality of medical information published online.


Multicenter Clinical Trials Analyzing Efficacy and Safety of Topical Cortex Phellodendri Compound Fluid in Treatment of Diabetic Foot Ulcers.
BACKGROUND The aim of this study was to analyze the clinical application of cortex phellodendri compound fluid (CPCF) in the treatment of diabetic foot ulcers. MATERIAL AND METHODS From January 2012 to December 2015, a total of 720 cases of diabetic foot ulcers (DFU) were randomly assigned into an experimental group (n=540) that was treated by CPCF and a control group (n=180) that was treated by a Kangfuxin solution (KFS). After 4 weeks of treatment, their ulcer area, serum growth factor, clinical total effective rate, and incidence of adverse events were assessed. RESULTS There were 720 patients who completed the trial. The experimental group was superior to the control group in reducing ulcer area, increasing growth factor content, and total effective rate (P<0.05). There was no significant difference in the adverse events rates between the 2 groups. CONCLUSIONS CPCF external treatment of diabetic foot ulcer can promote ulcer healing and increase the concentration of growth factors, and it is safe and reliable.


Structural connectome alterations in prodromal and de novo Parkinson's disease patients.
Although the clinical signs of prodromal Parkinson's disease (PD) have been identified, little is known about the neural features of the prodromal phase of PD (proPD). The aim of this study was to examine the structural network alterations from healthy aging to proPD and to early PD. 181 non-demented and non-depressed participants comprising 55 healthy controls (HCs), 20 proPDs, and 106 de novo PD patients (dPDs) were included in the study and underwent clinical assessment and diffusion tensor imaging scanning. Graph-theoretical analysis and network-based statistics, with age and gender as nuisance covariates, were used. Compared with HCs and dPDs, proPD patients showed significantly elevated small-worldness and clustering coefficient (Ps < 0.01) and greater local connectivity between regions relating to motor, olfactory and sleep functions (Ps < 0.05). Although dPDs and HCs did not differ on all graph-theoretic metrics, dPD patients showed decreased connectivity within the prefrontal regions and between the left temporal and occipital lobes (P < 0.05). The connectivity strength between these regions significantly distinguished between diagnostic groups. Connectivity between bilateral SMAs was correlated with UPSIT in HCs and with UPDRS-III in dPDs. Connectivity between the right SMA and putamen was correlated RBDSQ in proPDs. Increased network efficiency and connectivity of proPDs and decreased local connectivity of dPDs might suggest the emergence and dissipation of neural compensation in the prodromal phase and in early PD, respectively. Nonetheless, longitudinal studies are needed to follow up the long-term structural network changes of proPD patients.


Malignant deciduoid mesothelioma - to what extent is EUS useful?
An 83-year-old female presented with progressive dyspnea, a non-productive cough and right pleural effusion consistent with exudate. Rapid staining and PCR for mycobacteria, culture and cytology were negative. A thoracic computed tomography (CT) scan revealed a solid lesion, 53 mm in diameter, with an epicenter in the right crus of the diaphragm, both diaphragmatic and hepatic infiltration and compression of the inferior vena cava.


First detection of Pectenotoxin-11 and confirmation of OA-D8 diol-ester in Dinophysis acuta from European waters by LC-MS/MS.
During November 2005, a dense bloom of Dinophysis spp. dominated (>97%) by Dinophysis acuta in the Galician Rías Baixas (NW Spain), provided a unique opportunity to describe the full toxin profile - including toxins that represent a low percentage and escape detection in analyses of single-cell isolates - in plankton concentrates rich in this species. Detection and identification of toxins were carried out by liquid chromatography coupled to mass spectrometry (LC-MS/MS), a method that is based on their retention times (RT) and the fragmentation patterns of their mass spectra. OA-D8 diol-ester and PTX11 were detected in co-occurrence with okadaic acid analogues (OA, DTX2) and PTX2 in plankton concentrates dominated by D. acuta. The presence of a PTX11-isomer, which was suggested to be PTX13 or a novel PTX11-isomer, released in the sea water, was also confirmed in samples obtained after deployment of passive samplers (SPATT) in situ at the time of the D. acuta bloom maximum. The amount of PTX11 per cell of D. acuta, estimated as PTX2 equivalents, ranged between not detected and 2.2pg cell(-1), and represented a maximum of 2.9% of the total toxin content. The variation in PTX11 content per cell of D. acuta, during a daily cycle, followed the same pattern than that of PTX2, with maxima at 21:00 and 03:00h (dark hours), but the amounts per cell were one order of magnitude lower. This is the first report of PTX11, together with the confirmation of OA-D8 diol-ester in D. acuta populations from Europe.


[Perineo-transpubic approach in the treatment of traumatic rupture of the posterior urethra. Apropos of 14 cases].
Traumatic lesions of posterior urethra pose a problem in management because of the difficult access behind the pubic position. Twelve successful results among fourteen patients are treated by perineum transpubic surgery. The direct attack upon the lesion constitute the superiority of this approach.


Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.
We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.


A melatonin agonist and N-acetyl-N2-formyl-5-methoxykynurenamine accelerate the reentrainment of the melatonin rhythm following a phase advance of the light-dark cycle.
The rate of entrainment of the urinary 6-sulphatoxymelatonin rhythm to a phase-advanced photoperiod and the influence of a melatonin agonist and melatonin analogues and metabolites on the entrainment were investigated in male rats. Following an 8-h advance of a 14:10 light-dark photoperiod, the 6-sulphatoxymelatonin rhythm was disrupted completely for two days and became entrained after 5-6 days. Subcutaneous injection of the melatonin agonist, 6-chloromelatonin (0.5 mg/kg) and the brain metabolite, N-acetyl-N2-formyl-5-methoxykynurenamine (aFoMK, 10 mg/kg) two hours after dark onset on the day after the phase advance accelerated the entrainment to the new photoperiod. N-acetyl-5-methoxykynurenamine, 6-chloro-2,3-dihydromelatonin, 1,3-dihydro-5-(ethylacetamide)-7-methoxy-2H-1,4-benzodiazepin++ +-2-one and N-formylkynurenine were all without effect at a dose of 10 mg/kg. Treatment of rats with aFoMK on the day of the phase advance (day 0) together with treatment on day +1 accelerated the entrainment to the photoperiod whereas a single injection on day +2 or injections on day +1 and day +2 were without effect at a dose of 10 mg/kg. These results: (a) demonstrate the usefulness of monitoring urinary 6-sulphatoxymelatonin rhythms for pineal studies; (b) show that melatonin can indirectly influence its own secretion, presumably by interactions with the suprachiasmatic nucleus; and (c) provide further evidence for the biological activity of the brain metabolite of melatonin, N-acetyl-N2-formyl-5-methoxykynurenamine.


Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis.
During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease. We analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling. Transcripts of interleukin (IL)-1beta(β) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1β protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1β, IL-18 and IL-1α. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components. We demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis.


Intra-and intercolony patterns of nest dispersion in the ant Lasius neoniger: correlations with territoriality and foraging ecology.
Colonies of the ant Lasius neoniger have multiple nest entrances that are distributed throughout a colony's foraging area. Associated with each nest entrance is a group of workers that show strong fidelity to that nest entrance. Territorial expansion, as indicated by increases in the number of nest entrances per colony, is correlated with foraging activity. Although there is variation between colonies in the seasonal pattern of territorial expansion, most nests become active in early summer, increase the size of the area foraged until midsummer, and then decrease the number of active nest entrances in late summer. Over the study plot as a whole, the dispersion pattern of nest entrances changed from clumped, or tending to be clumped, in early spring to random in mid-and late summer. Within colonies, nest entrances were significantly overdispersed. Intra-and interspecific competition negatively affected foraging, and workers from a given nest entrance were most successful at retrieving prey less than approximately 15-20 cm from the entrance. The average distance between nest entrances within a colony was 37.7±3.3 cm (mean±95% confidence interval, n=115), which is approximately twice the distance at which workers can retrieve prey. The polydomous nest structure of L. neoniger appears to partition territory within a colony by spatial subdivision of its foragers, and thus may reduce loss of prey to competitors.


The 1989 morbidity and mortality meeting: how far have we come?
The Morbidity, Mortality, and Prescription of Dialysis Symposium was an international meeting held almost 9 years ago in Dallas, TX. The proceedings were subsequently published in the American Journal of Kidney Diseases. This article reviews key material from that meeting and evaluates what we have accomplished in the intervening years.


Improvement of foam breaking and oxygen-transfer performance in a stirred-tank fermenter.
This study examined a stirred-tank fermenter (STF) containing low-viscosity foaming liquids with an agitation impeller and foam-breaking impeller mounted on the same shaft. Results showed that the performance of the foam-breaking impeller can be improved by changing a conventional six-blade turbine impeller into a rod impeller as the agitation impeller. The volumetric oxygen-transfer coefficient, kLa, in the mechanical foam-control method (MFM) using a six-blade vaned disk as the foam-breaking impeller in the STF with the rod impeller was approximately five times greater than that of the chemical foam-control method (CFM) adding an anti-foaming agent in the STF with the six-blade turbine impeller. Application of the present method to the cultivation of Saccharomyces cerevisiae K-7 demonstrated that the cultivation time up to the maximum cell concentration was remarkably shorter than that achieved using a conventional CFM.


Hip Arthroplasty with Increased Expectancy.
The patient's demands and expectations after total hip arthroplasty have increased significantly. In particular, the athletic function is the focus of the patient's interest, whereby not the basic sports ability is inquired, but also the achievable sports level. The benefits of increased activity with a reduction in cardiovascular mortality and the minimization of osteoporosis risk are contrasted by amplified wear followed by prosthesis loosening. Activities are categorized in low-, intermediate- and high-impact kind of sport. Patient-based influencing factors such as physical condition and expertise in his sport, as well as the self-reference of the surgeon to the desired sport influence the recommendation and advice of the patient. Innovations in prosthesis design and materials technology allow meeting patient's expectations and aiming to improve the return to sport. After total hip arthroplasty, the majority of preoperatively active patients return to athletic activity, although there is a tendency to shift from "high-impact" to "low-impact" sports. The currently recommended sports include swimming, cycling, Nordic walking, sailing, golf, hiking, dancing and cross-country skiing. A limited recommendation exists for tennis (single), alpine skiing, mountain hiking and sportive running. Not recommended are marathon, football, handball, volleyball, basketball, martial arts, high jump, water skiing and rock climbing. The recommendations are based primarily on expert opinions and are in a progressive extension including "high-impact" sports.


Intraguild interactions among three spider mite predators: predation preference and effects on juvenile development and oviposition.
A first step to evaluate potential negative effects of intraguild predation (IGP) when using multiple predators against a pest species is the determination of the predation behavior of the predators and the nutritional value of intraguild (IG) prey in terms of development and oviposition. Here, we investigated the predation preference of the female predatory mites Neoseiulus californicus, Typhlodromus bagdasarjani and Phytoseius plumifer, when having choice between larvae of the two other predatory mite species (IG prey) with and without extraguild prey, the spider mite Tetranychus urticae (EG prey). Additionally, we evaluated the juvenile development and oviposition of the three predator species when provided with larvae from each other species. Irrespective of EG prey, IG prey species affected neither the first attack nor attack times of the three female IG predator species. The IG predation rates of the predator females, however, were influenced by prey species in the absence of EG prey. Neoseiulus californicus females killed more P. plumifer than T. bagdasarjani larvae, whereas T. bagdasarjani and P. plumifer females killed more N. californicus than P. plumifer and T. bagdasarjani larvae, respectively. All IG predator species consumed significantly more EG than IG prey. IG prey species did not influence juvenile and adult survival probabilities of the IG predators. We conclude that IGP is a weak force among the three predators and the potential consequences of IGP should not result in the elimination of one by another tested predatory mite species at least in the presence of spider mites.


Vasopressin and galanin expression in the hypothalamus of two African rodents, Taterillus gracilis and Steatomys caurinus, subjected to water-restriction.
The expression of arginine-vasopressin (AVP) and galanin (GAL) was studied by immunohistochemistry and in situ hybridization in the hypothalamus of two species of African rodents. In the wild, these animals experience successive arid and wet seasons that alternately stimulate their antidiuretic and diuretic systems. In this study, animals were subjected to both standardized laboratory conditions and to eight days of water-restriction. Under both sets of conditions, AVP and GAL were detected in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME). AVP and GAL responses to water-restriction differed in the two species, as did behavioral adaptations to the hot-dry season. In Taterillus gracilis, AVP- and GAL-LI (like immunoreactivity) peptide and mRNA levels increased in the SON. AVP-LI peptide and mRNA levels increased in the PVN, whereas only AVP-LI peptide levels increased in the ME. Pituitary gland AVP pools were unchanged by water deprivation, whereas urinary AVP levels and osmolality increased. The AVP response is typical of that of desert rodents, favoring survival under conditions of water-restriction. In Steatomys caurinus, which estivates, AVP and GAL-LI peptide levels decreased in the hypothalamus, as they did in the laboratory rat. In the SON, AVP, and GAL mRNA levels increased, whereas, in the PVN, only AVP mRNA levels increased. Pituitary gland AVP levels decreased, whereas urinary AVP levels and osmolality increased. In both species, the changes in the amount of GAL-LI peptide appeared to be closely linked to changes in AVP levels, suggesting that this peptide is involved in the osmoregulatory response to water-restriction.


Insights into the interaction of Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum, and Lomentospora prolificans with lung epithelial cells.
Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.


Hip Arthroscopic Surgery in the Context of Femoroacetabular Impingement Syndrome, Labral Tear, and Acetabular Overcoverage: Minimum 5-Year Outcomes With a Subanalysis Against Patients Without Overcoverage.
Improvement in patient-reported outcomes (PROs) has been reported in the short term after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and labral tear in the setting of acetabular overcoverage. Yet, there is a paucity of information in the literature on midterm PROs. To (1) report minimum 5-year PROs in patients who underwent primary hip arthroscopy for FAIS and acetabular labral tears in the context of acetabular overcoverage and (2) compare outcomes with those of a propensity-matched control group without acetabular overcoverage. Cohort study; Level of evidence, 3. Data were prospectively collected and retrospectively analyzed on all patients who underwent hip arthroscopy for FAIS and labral tears between February 2008 and November 2013. Inclusion criteria were lateral center-edge angle >40° and minimum 5-year follow-up for the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and the Hip Outcome Score-Sports-Specific Subscale (HOS-SSS). Exclusion criteria were previous ipsilateral hip surgery or conditions, active workers' compensation claims, or lack of minimum 5-year outcomes. A 1:1 propensity-matched comparison was made between the study group and a control group without acetabular overcoverage (lateral center-edge angle, 25°-40°) based on age at surgery, sex, body mass index, Tönnis grade, laterality, and follow-up time. The minimal clinically important difference (MCID) was calculated for the mHHS, HOS-SSS, and NAHS. Secondary surgical procedures were recorded. A total of 54 patients satisfied the inclusion criteria for the study group, of whom 45 (83.3%; 45 hips) had a minimum 5-year follow-up and were matched without differences in age at surgery, sex, body mass index, or follow-up time. The study and control groups demonstrated significant and comparable improvements for the mHHS (mean ± SD Δ, 24.06 ± 24.19 vs 26.33 ± 17.27; P = .625), NAHS (Δ, 31.22 ± 25.31 vs 27.15 ± 17.61; P = .399), and HOS-SSS (Δ, 33.16 ± 34.73 vs 34.75 ± 26.15; P = .557). The rates for achieving the MCID were similar for the study and control groups for the mHHS (76.7% vs 84.2%; P = .399), HOS-SSS (79.1% vs 75.8%; P = .731), and NAHS (81.4% vs 84.2%; P = .738). Need for revision surgery was similar (P = .748). A lower conversion rate to total hip arthroplasty was reported for the study than for the control group (2.2% vs 15.6%; P = .026). In the context of FAIS, labral tears, and acetabular overcoverage, patients who underwent hip arthroscopy reported significant improvement in several PROs at minimum 5-year follow-up. Moreover, outcomes were comparable with those of a propensity-matched control group without acetabular overcoverage. Furthermore, the rate of achieving the MCID for the mHHS, HOS-SSS, and NAHS was similar between these groups.


A sampling study of bedside nursing activity in a cardiac surgical intensive care unit. Part 1: Analysis of the elements of activity in the nursing workload, and its variation with patient age group and pathology.
For a selected group of 17 patients following cardiac surgery, 33 discrete elements of nursing workload have been defined. It was possible to identify 3 broad types of activity undertaken by the bedside nurse; technical nursing care (Type 1), intermittent nursing care (Type 2), and learning activities (Type 3). The latter is the balance of the nurses time which is largely concerned with observation and liaison with other staff. The 17 patients comprised 4 groups of pathologies, 2 each representative of the adult and paediatric workload. The primary bedside nurse performs virtually all of the Type 1 activities, recruiting the assistance of a secondary nurse principally to change the patients' posture (a Type 2 activity). The only practically significant period of time spent by the secondary nurse is in clinical discussion with the bedside nurse, largely at change of shift. Statistically significant differences in bedside nursing activities between age groups can be explained by the relative physical size of the patients and equipment. However the nurse maintains a higher level of awareness with shorter periods of inattention when nursing children. A greater number of significant differences between pathologies were found within the paediatric group of patients; this may indicate that a broader spectrum of such differences is to be found in this age group. An estimate was made of the impact of computer technology on the nurse's bedside workload.


Molecular Insights into Lipoxygenases in Diatoms Based on Structure Prediction: a Pioneering Study on Lipoxygenases Found in Pseudo-nitzschia arenysensis and Fragilariopsis cylindrus.
Diatoms produce a variety of oxylipins which are oxygenated polyunsaturated fatty acids and are involved in chemical defense and intercellular communication, among other roles. Although the chemistry of diatom oxylipins has long been studied, the enzymes involved in their production, in particular lipoxygenase (LOX), which catalyzes the initial reaction of the synthesis, have not been discovered in diatom genomes. Recently, diatom LOXs were found in two species, Pseudo-nitzschia arenysensis (PaLOX) and Fragilariopsis cylindrus (FcLOX); however, the enzymology of these LOXs is largely unknown. In this review article, we discuss the potential functions of the diatom LOXs based on previously reported structures of LOXs derived from various organisms other than diatoms. Since the structures of PaLOX and FcLOX have not yet been solved, we discussed their functions, such as regio- and stereospecificities, on the basis of their structures predicted using a computational tool based on deep learning technology. Both diatom LOXs were predicted to conserve common core domains with relatively wide substrate-binding pockets. The stereo-determinant residues in PaLOX and FcLOX suggest S specificity. We assume that the highly conserved common core domain can be a clue to reveal unidentified lox genes from the accumulated diatom genome information with the aid of high-throughput structure prediction tools and structure-based alignment tools in the near future.


Predictors of Compulsive Sexual Behavior Among Treatment-Seeking Women.
Compulsive Sexual Behavior Disorder is currently included in the forthcoming eleventh revision of the International Classification of Diseases (ICD-11); however, prior studies have been conducted mostly on heterosexual, White/European male samples. To examine the correlates of compulsive sexual behaviors (CSB) with sociodemographic and sexual history characteristics, as well as predictors of CSB in a sample of treatment-seeking Polish women. Six hundred seventy-four (674) Polish women aged 18-66 completed an online-based survey. Polish adaptation of the Sexual Addiction Screening Test-Revised (SAST-PL) was used to assess the severity of CSB symptoms. Brief Pornography Screen was used to measure problematic pornography use. The bivariate associations between SAST-PL scores and demographic and sexual history characteristics were also examined. A linear regression analysis was performed to identify variables related to the severity of CSB symptoms. Thirty one percent (31.8%) of women in the studied sample reported treatment seeking for CSB in the past. Problematic pornography use was the strongest predictor of CSB symptoms. Higher severity of CSB symptoms were observed among divorced/separated and single women compared to those who were married or in informal relation. Severity of CSB was positively related to the number of sexual partners during the last year, number of dyadic sexual intercourse during the last 7 days, and negatively associated with age of first sexual intercourse. Our results suggest that CSB is a significant concern among women and more research is needed to identify protective (eg, relationship status) and risk (eg, problematic pornography use, number of past year sexual partners, frequency of past week masturbation) factors associated with CSB symptom severity among treatment-seeking women. Our study is one of very few investigating predictors of CSB among women. Given the lack of precise estimates of the prevalence, as well as lack of psychometrically validated instruments measuring CSB in women, present findings should not be considered indicative of CSB prevalence among Polish women. The lack of clinical data on women reporting issues with CSB remains an important target for future clinical research exploration. Kowalewska E, Gola M, Lew-Starowicz M, et al. Predictors of Compulsive Sexual Behavior Among Treatment-Seeking Women. Sex Med 2022;10:100525.


Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.
In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT. Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+). Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively. MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.


[Exposure of a cohort of newborn infants to tuberculosis in a neonatology service].
A nursery nurse that was working in the neonatology service had been diagnosed with tuberculosis. As a consequence, the newborn infants were in danger of a possible contamination during a 4-month period. One hundred and thirty kids that had been in touch with the nurse were given attention. Prophylactic treatment for three months with isoniazid and rifampicin has been proposed to all families. Each of them was screened with a tuberculin sensitivity test and was given chest radiography initially and after three months. None of the children was initially suspected for tuberculosis. Among the chest radiographies, 97.6% were normal and all the intradermal tuberculin were either negative or in the norm following a vaccination by the Bacillus Calmette-Guerin. In most cases, the treatment tolerance was high. A 4-year-long surveillance ensured that no infant was infected. This procedure has established that the risk of transmission by a nurse is low, should it be for newborn babies, as long as guidelines are strictly adhered to.


Uterine artery Doppler at 11-14 weeks of gestation to screen for hypertensive disorders and associated complications in an unselected population.
To establish reference values for the first-trimester uterine artery (UtA) pulsatility index (PI) and to investigate the role of UtA Doppler in the early prediction of hypertensive disorders and their associated complications in an unselected Mediterranean population. A prospective study including 1091 consecutive singleton pregnancies undergoing routine early ultrasound screening at 11-14 weeks of gestation was performed. The left and right UtA were examined by color and pulsed Doppler transvaginally. The mean PI and the presence of bilateral protodiastolic notching were cross-sectionally recorded. Reference ranges were calculated and the pregnancies were followed for occurrence of pre-eclampsia, gestational hypertension, intrauterine growth restriction, placental abruption and stillbirth. The sensitivity and predictive values of a mean UtA-PI>95th percentile and the presence of bilateral notching in the prediction of these pregnancy complications were calculated. A total of 999 women were finally included. Both the mean UtA-PI and the prevalence of bilateral notches showed a significant linear decrease between 11 and 14 weeks' gestation. Sixty-seven (6.7%) pregnancies developed at least one of the formerly described complications, including 22 (2.2%) cases of pre-eclampsia and 37 (3.7%) cases with intrauterine growth restriction. Compared with women with a normal outcome, complicated pregnancies showed a significantly higher mean PI (2.04 vs. 1.75; P<0.05, t-test) and a higher prevalence of bilateral notching (58% vs. 41%; P<0.05, Chi-square test). Using the 95th percentile in mean UtA-PI as a cut-off, 23.9% (95% CI, 13.7-34.1) of complicated pregnancies and 30.8% (95% CI, 5.68-55.85) of severe cases were identified. Our results suggest that pregnancies with an increased risk of developing hypertensive disorders and related complications already have an abnormally increased UtA-PI in early pregnancy. However, the use of a single uterine Doppler measurement for screening purposes in unselected early pregnancy populations has limited clinical value. The use of UtA-PI combined with other screening tests needs to be determined by further investigation.


A new expanded solubility parameter approach.
The partial or Hansen solubility parameters (HSP) are important properties of the various substances and very useful tools for the selection of their solvents or the prediction of their behaviour in numerous applications. Their design and evaluation relies on the basic rule of "similarity matching" for solubility. The present work attempts to enhance the capacity of HSPs by incorporating into their evaluation the other basic rule of solubility, namely, the rule of "complementarity matching". This is done in a simple and straightforward manner by splitting the hydrogen bonding HSP into its acidic or proton donor component and its basic or proton acceptor one. The splitting is based on the third σ-moments of the screening charge distributions or sigma profiles of the quantum-mechanics based COSMO-RS theory. The whole development and application does not involve any sophisticated calculations or any strong specific background. The new method has been applied to a variety of solubility data for systems of pharmaceutical interest in order to verify the significant improvement over the classical HSP approach. The application of the new method requires, of course, the knowledge of the HSPs. For this reason, in Appendix A is presented an updated version of a robust and reliable group-contribution method for the calculation of the HSPs. The key features of this combined tool are critically discussed.


Case report: a case report and literature analysis on intestinal tuberculosis intestinal perforation complicated by umbilical intestinal fistula and bladder ileal fistula.
Intestinal tuberculosis is a chronic and specific infection caused by Mycobacterium tuberculosis invading the intestine. Due to the nonspecific clinical presentation, it is stressed that intestinal perforation complicates umbilical intestinal fistula and bladder ileal fistula is very rare and extremely difficult to be diagnosed. It is significant to identify the disease and take urgent intervene in the early stage. An 18-month-old boy patient presented with abdominal pain. Abdominal CT suggested abscess formation in the right lower abdomen and pelvis. The patient underwent resection of necrotic and stenotic intestinal segments with the creation of an ileostomy, cystostomy and vesicoureteral fistula repair for the presence of intestinal perforation complicated by vesicoureteral fistula and umbilical enterocutaneous fistula. Histopathology confirmed the intestinal tuberculosis. The patient was discharged successfully after 11 days post anti-tuberculosis treatment. Our case report here is a rare case of umbilical intestinal fistula with bladder ileal fistula secondary to intestinal perforation from intestinal tuberculosis. The purpose of this report is to make the surgical community aware of atypical presentations of intestinal tuberculosis. If our peers encounter the similar situation, they can be prepared for corresponding diagnosis and treatment.


CD8+ T cells in Trypanosoma cruzi infection.
Trypanosoma cruzi infection and Chagas disease remains among the most neglected of the neglected tropical diseases. Despite this, studies of the immune response to T. cruzi have provided new insights in immunology and guidance for approaches for prevention and treatment of the disease. T. cruzi represents one of the very best systems in which to study CD8(+) T cell biology; mice, dogs, and primates (and many other mammals) are all natural hosts for this parasite, the robust T cell responses generated in these hosts can be readily monitored using the full range of cutting edge techniques, and the parasite can be easily modified to express (or not) a variety of tags, reporters, immune enhances, and endogenous or model antigens. The infection in most hosts is characterized by vigorous and largely effective immune responses, including CD8(+) T cells capable of controlling T. cruzi at the level of the infected host cells. However, this immune control is only partially effective and most hosts maintain a low level infection for life. This review addresses the interplay of highly effective CD8(+) T cell responses with elaborate pathogen immune evasion mechanisms, including the generation and simultaneous expression of highly variant CD8(+) T cell targets and a host cell invasion mechanisms that largely eludes innate immune detection.


The influence of repeated flares in response to therapy and prognosis in lupus nephritis.
Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.


Alkali-labile oligosaccharide units of a sialoglycoprotein from rabbit erythrocyte membranes.
Two glycoproteins (apparent molecular weights 120,000 and 70,000) were extracted from rabbit erythrocyte membranes, and only one (Mr 120,000), which is a sialoglycoprotein, contained O-glycosidically linked sugar chains. Alkali-labile oligosaccharide units of the sialoglycoprotein were released as reduced oligosaccharides by NaOH-NaB3H4 treatment, and then purified by gel filtration on a Bio-Gel P-4 column followed by ion-exchange chromatography. From the results of methylation analysis, mass spectrometry and chromium trioxide oxidation, the main oligosaccharide unit was determined to be a linear trisaccharide (85% by weight), NeuNGc alpha(2----3)Gal beta(1----3)GalNAcol. In addition, small amounts of a tetrasaccharide (11% by weight) and a disaccharide (4% by weight) were found, which were determined to have the following structures, NeuNGc alpha(2----3)Gal beta(1----3)[NeuNGc alpha(2----6)] GalNAcol and Gal-GalNAcol, respectively.


Strangulation of upper jejunum in subsequent pregnancy following gastric bypass surgery.
Gastric bypass is a surgical procedure that is popularly used to treat morbid obesity. Herein, we report a woman who had a rare gastrointestinal complication during the subsequent antepartum period following a gastric bypass surgery. After a Roux-en-Y gastric bypass surgery, a 32-year-old woman had unrelenting epigastria for one week at 36 weeks' gestation. An emergency cesarean delivery, followed by laparotomy, was performed. A female neonate was delivered with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Strangulation and gangrene of the upper jejunum caused by a fibrous band at the site of the Roux anastomosis were revealed. Segmental resection of the nonviable bowel was performed. The patient experienced a smooth postoperative course. The awareness of internal hernias and small bowel strangulation should be addressed when unrelenting epigastric pain is present in women after Roux-en-Y gastric bypass surgery, during their first subsequent pregnancy.


Low-dose bacille Calmette-Guérin for non-muscle-invasive bladder cancer: Results of a prospective study.
To evaluate the efficacy and safety of low-dose (45 mg) intravesical bacille Calmette-Guérin (BCG) therapy in the treatment of patients with non-muscle-invasive bladder cancer (NMIBC), as intravesical BCG is the most acceptable adjuvant therapy for NMI transitional cell carcinoma of the bladder. However, in the standard regimen, undesirable effects are the main cause of treatment discontinuation. The present study included 37 men with primary NIMBC. All patients underwent complete TURB and 2 weeks later, a 6-week course of 45 mg BCG diluted in 50 mL isotonic saline was instilled into the bladder and retained for 2 h. Patients were evaluated for BCG efficacy (recurrence with or without progression) and safety by documentation of minor and/or major side-effects. There were no major or severe side-effects and no treatment discontinuations. Local adverse effects occurred in 20 patients, while systemic effects, in the form of fever, occurred in six patients (16.2%). There was recurrence in 14 patients (37.8%) after 18-34 months, with disease progression (muscle invasion) in four (10.8%) after 6-18 months. The recurrence index was 0.39/100 patients/month and the mean (range) tumour-free period was 30.97 (7-36) months. Low-dose BCG intravesical therapy is an effective adjuvant treatment in NMIBC. However, this needs to be validated in future studies and in comparison with other proposed doses and/or regimens.


Absence of vesico-ureteral reflux in children with ureteral jets.
The jet phenomenon is a normal finding in excretory urography. The presence of such a jet is a good sign that vesico-ureteral reflux is not present. Of 19 ureters with a jet sign, only one had minimal transient ureteral reflux, while in 39 ureters without a jet sign 15 had reflux.


Distribution of a novel pituitary protein (7B2) in mammalian gastrointestinal tract and pancreas.
The distribution of a novel pituitary protein (7B2) was determined in the gastrointestinal tract and pancreas of four mammalian species (man, pig, guinea pig, and rat) by a specific radioimmunoassay. The highest concentrations of cross-reacting immunoreactive 7B2 (IR-7B2) were observed in the pancreas and the proximal gut (antrum or duodenum). While the intestinal concentrations varied widely among species, pancreatic IR-7B2 concentrations appeared to be similar in all four species. In the rat, pancreatic islets were found to contain high concentrations of IR-7B2 (5.73 +/- 0.14 fmol/islet, mean +/- SEM). Neonatal capsaicin treatment and enteric nerve section did not affect the concentrations of IR-7B2 in the rat intestine. Layer separation of human gut showed that IR-7B2 is mainly (71 +/- 8%) present in the epithelial fraction. Chromatographic analysis of intestinal and pancreatic extracts from the four species on Sephadex G-100 showed the presence of two immunoreactive peaks at Kav 0.3 and 0.6, but there were both inter- and intraspecies variations in the proportions of the larger and smaller molecular forms.


Non-Hodgkin's lymphoma of the thyroid.
Twenty-eight patients with non-Hodgkin's lymphoma of the thyroid were treated between 1954 and 1981. The duration of follow-up ranged from 39 to 176 months. The overall 5 year survival was 51%. Twenty deaths have been recorded of which 12 were attributed to non-Hodgkin's lymphoma. Eight patients relapsed following initial treatment. Of these, two patients are long term survivors and the remainder had a mean survival of 14.5 months. The histology was reviewed by one histopathologist, with 88% of the cases being classified as grade 2 non-Hodgkin's lymphoma. The presence of Hashimoto's thyroiditis was identified in 56% of the 25 assessable specimens.


Effects of plasma total ammonia content and pH on urea excretion in Nile tilapia.
Nile tilapia (Oreochromis niloticus) were infused with ammonium salts, acid, and base to investigate the effects of changes in arterial plasma total ammonia content (Tamm) and pH (pHa) on plasma urea-nitrogen (urea-N) levels and urea-N excretory fluxes (Jurea-N). The tilapia did not possess a functional hepatic ornithine urea-cycle (no significant carbamyl phosphate synthetase III activity). Infused substances were dissolved in a saline vehicle and injected twice (5 mL kg-1), the first infusion to "prime" the animal and promote a more marked response to the second infusion, given 2.5 h later. The results reported are those of the second infusion. Infusion of 200 mM NH4Cl increased Tamm, reduced pHa, and increased plasma urea-N and Jurea-N. Two hundred mM NH4HCO3 increased Tamm and arterial plasma total CO2 content (TaCO2), reduced pHa, and increased Jurea-N. Fifty mM HCl reduced pHa but had no effects on urea dynamics. Fifty mM NaOH increased pHa, plasma urea-N levels, and Jurea-N. Two hundred mM NaHCO3 increased pHa, TaCO2, plasma urea-N levels, and Jurea-N. Infusion of the saline vehicle was without effect. The results indicate that ammonia loading and plasma alkalosis both stimulate urea excretion in uricolytic fish. The responses to hyperammonemia or alkalosis were not modified when combined with elevated plasma bicarbonate levels.


Surface characteristics of adenocarcinoma of the uterine cervix.
The purpose of this study was to analyze the development and classification of cervical adenocarcinoma as seen by scanning electron microscopy (SEM) and correlate the result to morphological alterations in cervical squamous cell carcinoma and endometrial adenocarcinoma. The results showed the endocervical area to be covered by a single layer of columnar cells, some with cilia, containing numerous folds and clefts, but no real glandular structures. The surface of malignant tumors consisted of pavelike arrangements of grooves and clefts covered with blunt microvillous processes, shorter and less delicate than those found on normal columnar cells. The surface microridges of squamous cells were replaced by irregular projections in squamous malignancy and endometrial adenocarcinoma showed a more undulating endometrial appearance.


Impact and effectiveness of a mass hepatitis A vaccination programme of preadolescents seven years after introduction.
To investigate the impact of a mass hepatitis A vaccination programme in preadolescents seven years after introduction in terms of its effectiveness and the prevented fraction. The age distribution of notified cases and incidence rates in Catalonia (Spain) in the periods before (1992-1998) and after (1999-2005) introduction of the vaccination programme were compared. The incidence rates in the whole population were 5.51 per 100,000 person-years in the 1992-1998 period and 2.98 in the 1999-2005 period. The rate reduction in the 10-19 years age group was 72.43% and was more than 45% in the 5-9 years and 20-29 years age groups. The effectiveness of the vaccination programme was 99.04 (95% CI: 93.11-99.88) and the prevented fraction in the 12-19 years age group was 90.13% (95% CI: 84.47-90.89). The universal vaccination programme of preadolescents has had an important impact on hepatitis A in Catalonia, not only in vaccinated cohorts but also in non-vaccinated age groups due to a herd immunity effect.


ETU-Net: efficient Transformer and convolutional U-style connected attention segmentation network applied to endoscopic image of epistaxis.
Epistaxis is a typical presentation in the otolaryngology and emergency department. When compressive therapy fails, directive nasal cautery is necessary, which strongly recommended operating under the nasal endoscope if it is possible. Limited by the operator's clinical experience, complications such as recurrence, nasal ulcer, and septum perforation may occur due to insufficient or excessive cautery. At present, deep learning technology is widely used in the medical field because of its accurate and efficient recognition ability, but it is still blank in the research of epistaxis. In this work, we first gathered and retrieved the Nasal Bleeding dataset, which was annotated and confirmed by many clinical specialists, filling a void in this sector. Second, we created ETU-Net, a deep learning model that smartly integrated the excellent performance of attention convolution with Transformer, overcoming the traditional model's difficulties in capturing contextual feature information and insufficient sequence modeling skills in picture segmentation. On the Nasal Bleeding dataset, our proposed model outperforms all others models that we tested. The segmentation recognition index, Intersection over Union, and F1-Score were 94.57 and 97.15%. Ultimately, we summarized effective ways of combining artificial intelligence with medical treatment and tested it on multiple general datasets to prove its feasibility. The results show that our method has good domain adaptability and has a cutting-edge reference for future medical technology development.


Genetic variation in fatty acid amide hydrolase (FAAH): Associations with early drinking and smoking behaviors.
The endocannabinoid system is implicated in psychiatric disorders and drug dependence. Within this system, fatty acid amide hydrolase (FAAH) metabolizes endocannabinoids. Individuals with A-group genotypes (C/A or A/A) of a common FAAH variant (rs324420; C > A; Pro129Thr) have slower enzymatic activity compared to C-group individuals (C/C genotype). Slow FAAH activity is differentially associated with alcohol and nicotine use. Among European-ancestry participants in the NDIT study (n = 249-607), genotype associations with past-year binge drinking in young adults were estimated in logistic regression models. In adolescents, hazard ratios (HR) were estimated from Cox proportional hazards models to assess the FAAH genotype group association with time to drinking initiation and attaining drinking frequency outcomes. HR were also used to assess genotype effect on time to smoking initiation and attaining early smoking milestones (e.g., first inhalation, ICD-10 dependence). Compared to those in the C-group, those in the A-group had higher odds of binge drinking at ages 20 (Odds ratio (OR) = 2.16, 95 % CI 1.36-3.42) and 30 (OR = 1.61, 95 % CI 1.10-2.36). Time to initiation of drinking and daily drinking was faster in adolescents in the A-group (HR = 1.39, 95 % CI 1.09-1.77 and HR = 2.24, 95 % CI 1.05-4.76, respectively). Time to smoking initiation was faster in the A-group (HR = 1.20, 95 % CI 1.04-1.39); however, time to smoking milestones among adolescent smokers was not consistently different for the A- versus C-groups (HR = 0.43 to 1.13). Slow FAAH activity (A-group) was associated with greater risks for binge drinking, drinking initiation and escalation, and cigarette smoking initiation, but had little impact on the escalation in cigarette smoking behaviors.


[Association analysis between attention-deficit hyperactivity disorder and Val158Met polymorphism of catechol-O-methyltransferase gene].
To investigate the association between attention-deficit hyperactivity disorder (ADHD) in Han Chinese children and Val158Met polymorphism of catechol-O-methyltransferase (COMT) gene caused by the missense mutation of G158A in exon 4. By using polymerase chain reaction-restriction fragment length polymorphisms the Val158Met polymorphism of COMT gene was tested in 117 children with the diagnosis of ADHD as defined by DSM-IV and in 105 healthy controls living in Shanghai. The frequencies of A allele were 25.21% and 23.81% in the ADHD group and the health controls respectively, which showed no significant difference between the two groups (Chi2=0.5197, P>0.05). There was also no significant difference in the distribution of all genotypes of COMT gene between the ADHD patients and the controls (P>0.05). It was suggested that for the Han Chinese children with ADHD in this study, there was no association between ADHD and Val158Met polymorphism of COMT gene.


PSA density in the diagnosis of prostate cancer in the Chinese population: results from the Chinese Prostate Cancer Consortium.
We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with prostate-specific antigen (PSA) levels ≥4.0 ng ml-1 regardless of digital rectal examination (DRE) results or PSA levels <4.0 ng ml-1 and abnormal DRE results were included from 18 large referral hospitals in China. The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer (PCa) and high-grade prostate cancer (HGPCa) at different cutoff values were evaluated. A total of 5220 patients were included in the study, and 2014 (38.6%) of them were diagnosed with PCa. In patients with PSA levels ranging from 4.0 to 10.0 ng ml-1, PSAD was associated with PCa and HGPCa in both univariate (odds ratio [OR] = 45.15, P < 0.0001 and OR = 25.38, P < 0.0001, respectively) and multivariate analyses (OR = 52.55, P < 0.0001 and OR = 26.05, P < 0.0001, respectively). The areas under the receiver operating characteristic curves (AUCs) of PSAD in predicting PCa and HGPCa were 0.627 and 0.630, respectively. With the PSAD cutoff of 0.10 ng ml-2, we obtained a sensitivity of 88.7% for PCa, and nearly all (89.9%) HGPCa cases could be detected and biopsies could be avoided in 20.2% of the patients (359/1776 cases). Among these patients who avoided biopsies, only 30 cases had HGPCa. We recommend 0.10 ng ml-2 as the proper cutoff value of PSAD, which will obtain a sensitivity of nearly 90% for both PCa and HGPCa. The results of this study should be validated in prospective, population-based multicenter studies.


Provider Attitudes and Screening Practices Following Changes in Breast and Cervical Cancer Screening Guidelines.
Changes to national guidelines for breast and cervical cancer screening have created confusion and controversy for women and their primary care providers. To characterize women's primary health care provider attitudes towards screening and changes in practice in response to recent revisions in guidelines for breast and cervical cancer screening. In 2014, we distributed a confidential web and mail survey to 668 women's health care providers affiliated with the four clinical care networks participating in the three PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium breast cancer research centers (385 respondents; response rate 57.6 %). We assessed self-reported attitudes toward breast and cervical cancer screening, as well as practice changes in response to the most recent revisions of the U.S. Preventive Services Task Force (USPSTF) recommendations. The majority of providers believed that mammography screening was effective for reducing cancer mortality among women ages 40-74 years, and that Papanicolaou (Pap) testing was very effective for women ages 21-64 years. While the USPSTF breast and cervical cancer screening recommendations were widely perceived by the respondents as influential, 75.7 and 41.2 % of providers (for mammography and cervical cancer screening, respectively) reported screening practices in excess of those recommended by USPSTF. Provider-reported barriers to concordance with guideline recommendations included: patient concerns (74 and 36 % for breast and cervical, respectively), provider disagreement with the recommendations (50 and 14 %), health system measurement of a provider's screening practices that use conflicting measurement criteria (40 and 21 %), concern about malpractice risk (33 and 11 %), and lack of time to discuss the benefits and harms with their patients (17 and 8 %). Primary care providers do not consistently follow recent USPSTF breast and cervical cancer screening recommendations, despite noting that these guidelines are influential.


Evaluation of factors impacting patient satisfaction in a pediatric otolaryngology clinic.
With an emphasis on patient-centered care and provider transparency, patient satisfaction measures have become a key indicator of healthcare quality. Using the Press Ganey Outpatient Medical Practice Survey (PGOMPS), we sought to determine key factors that impact patient satisfaction. We conducted a retrospective review of new pediatric (<18 years old) outpatient otolaryngology visits between January 1, 2014 and December 31, 2018 at a children's hospital clinic and satellite clinics. Univariate and multivariate binary logistic regression analysis were used to determine factors correlated with patient satisfaction for both the PGOMPS Total Score and Provider Sub-Score. A total of 1,050 patient or parent responses were included. The mean patient age was 5.6 ± 5.0 years with 54.7% identified as male. Univariate analysis demonstrated that for each 10-min increase in Total Wait Time, the odds of being satisfied were significantly decreased on both the Total Score (odds ratio [OR] 0.5; P < 0.001) and Provider Sub-Score (OR 0.8; P < 0.001). Furthermore, for each additional 5-year increase in patient age, patients were significantly more likely to report satisfaction on Total Score (OR 1.21; P = 0.011). Multivariate analysis revealed that the odds of achieving satisfaction for each decile increase in Total Wait Time were 0.5 for Total Score (P < 0.001) and 0.8 for Provider Sub-Score (P < 0.001), independent of patient age, sex, insurance category, socioeconomic disadvantage level, and patient community type. Wait time is a significant factor impacting patients' likelihood of being satisfied with their overall care in a pediatric otolaryngology clinic setting.


LET distributions from CR-39 plates on Space Shuttle missions STS-84 and STS-91 and a comparison of the results of the CR-39 plates with those of RRMD-II and RRMD-III telescopes.
The LET distributions during the Space Shuttle missions STS-84 (altitude 270-412 km, average 375 km; inclination angle, 51.6 degrees) and STS-91 (altitude 328-397 km, average 373 km; inclination angle, 51.6 degrees) were measured using CR-39 plastic nuclear track detectors. A correction for the dip-angle dependence of the track-formation sensitivity of the CR-39 plates was applied to the data analysis. The absorbed doses and the dose equivalents around RRMD Detector Units, estimated from the LET distributions in the LET region of 4-200 keV/micrometers, fluctuated with standard deviations of +/- 21% to +/- 35% in both flight experiments. The LET distributions obtained from the CR-39 plates agreed well with that obtained from RRMD-II in STS-91. However, the particle fluxes obtained from RRMD-III in STS-84 and STS-91 were two or three times higher than those obtained from RRMD-II and the CR-39 plates. It was concluded that the LET distributions obtained from RRMD-II and the CR-39 plates in the present flight experiments did not include the contribution of target-fragmented secondary heavy particles produced by low-LET particles, such as relativistic or semi-relativistic protons and helium ions, whereas RRMD-III was able to detect these secondary particles because of its low triggering level.


Seed treatment and foliar application of methyl salicylate (MeSA) as a defense mechanism in rice plants against the pathogenic bacterium, Xanthomonas oryzae pv. oryzae.
Methyl salicylate (MeSA) is a volatile biological compound synthesized from salicylic acid (SA) and is a plant hormone that helps defend against pests and pathogens. A major bacterial pathogen of rice, Xanthomonas oryzae pv. oryzae (Xoo) causes severe disease. Seed and plant treatments with MeSA can stimulate the defense enzyme peroxidase (POD) in plants. Response of peroxidase activity in rice (Oryza sativa L) cultivars IR 20, IR 50, IR 64, ASD 16, ASD 19 and ADT 46 to MeSA were measured under greenhouse conditions. Treatments of rice seedlings with MeSA at 50 and 100 mg L-1 significantly upregulated POD expression in the plants. The activity of POD was also significantly upregulated when plants were inoculated with bacterial blight. Effects were stronger in ASD 16, ASD 19 and ADT 46 and were more pronounced in high dose treatment (100 mg L-1) when inoculated with bacterial blight condition and the effects were dose dependent, although the relationship between dose and rice varieties were not always linear. The pathogenic related (PR) protein bands at 33 kDa and 14 kDa were identified in treatments of 100 mg L-1 MeSA in the presence of bacterial blight disease. Band intensity was estimated to be twice that of those from pathogen induce MeSA levels in rice plants. These results suggest that treatment with MeSA can significantly increase the POD defense related enzyme by altering the plant physiology in ways that may be beneficial for crop protection.


Real-time reverse transcription-polymerase chain reaction assays for identification of wild poliovirus 1 & 3.
The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use. Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre. No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 10 4.40 CCID 50 /ml of WPV1 and 10 4.00 CCID 50 /ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus. rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures.


Increase of Antimyeloperoxidase Antineutrophil Cytoplasmic Antibody (ANCA) in Patients with Renal ANCA-associated Vasculitis: Association with Risk to Relapse.
The diagnostic values of antiproteinase 3 and antimyeloperoxidase tests using antineutrophil cytoplasmic antibodies (ANCA) are well established. Our study determined whether an increase in ANCA level was a predictor of disease flareup. Our study included 126 patients with ANCA-associated renal vasculitis treated at 9 nephrology centers in Japan. The relationship between increased ANCA levels and relapse was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. The outcome of interest was the time from remission to first relapse. During the observation period [median 41 mos, interquartile range (IQR) 23-66 mos], 118 patients (95.8%) achieved remission at least once. After achieving remission, 34 patients relapsed (21.7%). Time-dependent multivariate Cox regression models revealed that lung involvement (adjusted HR 2.29, 95% CI 1.13-4.65, p = 0.022) and increased ANCA levels (adjusted HR 17.4, 95% CI 8.42-36.0, p < 0.001) were significantly associated with relapse. The median time from ANCA level increase to relapse was 0.6 months (IQR 0-2.1 mos). In our study, an increase in ANCA level during remission was associated with a risk of disease relapse. A rise in ANCA level may be useful for guiding treatment decisions in appropriate subsets of patients with ANCA-associated vasculitis.