Application of liver acquisition with volume acceleration enhanced sequence in improving the accuracy of reassessing organ-invasive rectal mucinous adenocarcinoma after chemoradiation.
To explore the ability of liver acquisition with volume acceleration contrast-enhanced sequence (LAVA-ce) to improve the accuracy of reassessing adjacent organ involvement by rectal mucinous adenocarcinoma (MC) after neoadjuvant therapy (NAT). This study retrospectively enrolled twenty-five patients with MC who underwent pre- and post-NAT MRI, were staged as T4b using pre-NAT T2 weighted imaging, received NAT and underwent radical resection. All MR images were divided into two schemes, T2 weighted plus diffusion weighted imaging (T2Dw protocol) and plus LAVA-ce (T2DwLce protocol). All patients were scored on a 0-4 scale to reassess organ-invasive mucus components. Postoperative pathology was used to identify the involvement of surrounding organs (ypT4b). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the consistency of the results with pathology after adding fs-CE sequence. Among 25 MC patients (15 males and 10 females, aged 21-89 years), 21 were restaged as yT4b after NAT by using T2Dw, with an accuracy of 44.0 % (11/25), which was lower than the accuracy of staging patients with non-mucinous rectal adenocarcinoma (94.1 %, 96/102). The accuracy of MC restaging was improved by using T2DwLce (23/25). The AUC of T2DwLce was 0.857 (95 % CI, 0.660∼0.964), which was higher than that of T2Dw (AUC, 0.611 [95 % CI, 0.397∼0.798]) (P = 0.019). The LAVA-ce sequence can improve the accuracy of reevaluation and should be included in the MRI protocol for MC patients.


Role of the aryl hydrocarbon receptor and Cyp1b1 in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The role of aryl hydrocarbon receptor (AhR) and cytochrome P450 (Cyp) 1 family in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) was investigated in vivo. Immature (21 days old) AhR, Cyp1a2, or Cyp1b1 knockout (-/-) mice were treated intraperitoneally with estradiol (E2, 20 ng/mouse per day, for 14 consecutive days) and/or TCDD (200 ng/mouse per day, on days 7, 9, 11, and 13). Uterine wet weight and uterine peroxidase activity (UPA) were measured as markers of estrogen responsiveness. UPA was a better marker of estrogen responsiveness than the uterine wet weight. In AhR wild-type (+/+) mice, UPA (208.1+/-81.6 units/g tissue) was increased by the administration of E2 (to 297.2+/-178.7 units/g). The administration of TCDD significantly ( p<0.01) decreased the UPA (10.5+/-3.4 units/g) compared with that in the control mice. Co-administration of TCDD with E2 also significantly ( p<0.05) decreased the UPA (18.8+/-19.9 units/g) compared with that in E2-treated mice. In AhR(-/-) mice, UPA (162.9+/-146.7 units/g) was significantly ( p<0.01) increased by the administration of E2 (486.8+/-108.2 units/g). In contrast to the results in AhR(+/+) mice, UPA was not affected by the administration of TCDD (51.8+/-70.6 units/g) compared with control, and co-administration of TCDD with E2 (545.8+/-189.4 units/g) compared with that in E2-treated mice. In Cyp1a2/1b1(+/+) mice, UPA was significantly ( p<0.05) increased by the administration of E2 (70.0+/-36.4 units/g). Co-administration of TCDD with E2 significantly ( p<0.05) decreased the UPA (29.6+/-22.2 units/g) compared with that in E2-treated mice. In Cyp1a2(-/-) mice, co-administration of TCDD with E2 significantly ( p<0.01) decreased the UPA (6.8+/-5.1 units/g) compared with that in E2-treated mice. In Cyp1b1(-/-) mice, UPA (5.5+/-8.1 units/g) was significantly ( p<0.05) increased by the administration of E2 (56.6+/-34.1 units/g). In contrast to the results in Cyp1a2/1b1(+/+) mice or Cyp1a2(-/-) mice, UPA was not affected by the co-administration of TCDD and E2 (52.6+/-30.1 units/g) compared with that in E2-treated mice. This is the first demonstration that Cyp1b1 as well as AhR is involved in the antiestrogenic effects of TCDD.


Development and validation of a tool for predicting type 2 diabetes in Mexican women of reproductive age.
Diabetes is a worldwide problem with a greater impact in developing countries, where many people are unaware of their risk. In Mexico, women show the greatest risk for T2D. Current risk scores have been developed and validated in predominantly older European cohorts. They are not the best option in Mexican women. The development of a risk model/score in this population would be useful. To develop and validate a risk model and score that incorporates the most relevant risk factors for T2D in Mexican women of reproductive age. The study was carried out in two phases, with the first phase being the development of the predictive model and the second phase the validation of the model in a separate independent population. A cohort of Mexican patients of reproductive age ("Derivation Cohort") was used to create the predictive model. It included data on 3161 women. Risk factors for identification were assessed using Cox proportional hazards regression. Finally a score with a range of 0 to 19 points was developed to identify the 2.4 year probability of developing DM2 in Mexican women of reproductive age. 147 new cases of T2D (4.6%) were identified in the Derivation Cohort model, 97 of 925 participants (10.48%) in the validation cohort. The risk factor predictors of T2D were: history of gestational diabetes (HR 2.69, 95% CI 1.10-6.58), BMI (HR 1.03, 95% CI 1.01-1.06), hypertriglyceridemia (HR 1.54, 95% CI 1.11-2.14) and fasting blood glucose (HR 1.06, 95% CI 1.05-1.08), with an AUC of 0.75. The AUC in the validation cohort was 0.91 (95% CI 0.87-0.94). The score had a sensitivity of 73% and specificity of 67% at a cutoff of ≥15. A predictive model and risk score was developed to detect cases at risk for incident T2D. It was generated using the characteristics of Mexican women of reproductive age. This risk score is a step forward in attempting to address the generational legacy that diabetes in pregnancy could have on women and their children.


Chondroitin/dermatan sulfate proteoglycan in human fetal membranes. Demonstration of an antigenically similar proteoglycan in fibroblasts.
A proteoglycan was isolated from fetal membranes which had been separated from human postpartum placenta. The glycosaminoglycan side chains (Mr = 55,000) were found to be composed of 75% chondroitin sulfate and 23% dermatan sulfate as determined by chondroitinase ABC or AC II digestion. NH2-terminal microsequencing of the intact proteoglycan revealed a single amino acid sequence of (sequence; see text) A rabbit antiserum raised against the intact proteoglycan reacted in sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting with Mr = 45,000 and 43,000 core polypeptides from chondroitinase-treated proteoglycan. Affinity-purified antibodies from this antiserum precipitated from human embryonic fibroblast culture fluid a proteoglycan which has an approximate Mr = 120,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This proteoglycan has on the average two polysaccharide side chains. As defined by chondroitinase digestion, these chains consist of 66% dermatan sulfate and 20% chondroitin sulfate. Digestion of the glycosaminoglycan with chondroitinase ABC converted the proteoglycan to a Mr = 45,000 major and a Mr = 43,000 minor core polypeptide. Tissue immunofluorescence localized the proteoglycan to interstitial matrices, suggesting that it is a product of mesenchymal cells. The methods we have devised for the purification of the fetal membrane proteoglycan in chemical amounts and the antibodies we have prepared against it will allow studies on the structural and functional properties of the proteoglycan and on the expression of immunologically cross-reactive proteoglycans by various cells and tissues.


A new feature selection method based on symmetrical uncertainty and interaction gain.
Defining important information from complex biological data is of great significance in biological study. It is known that the physiological and pathological changes in an organism are usually influenced by molecule interactions. Analyzing biological data by fusing the evaluation of the individual molecules and molecule interactions could induce a more accurate and comprehensive understanding of the organism. This study proposes an Interaction Gain - Recursive Feature Elimination (IG-RFE) method which evaluates the feature importance by combining the relevance between feature and class label and the interaction among features. Symmetrical uncertainty is adopted to measure the relevance between feature and the class label. The average normalized interaction gain of feature f, every other features and the class label is calculated to reflect the interaction of feature f with other features in the feature set F. Based on the combination of symmetrical uncertainty and normalized interaction gain, less important features are removed iteratively. To show the performance of IG-RFE, it was compared with seven efficient feature selection methods, MIFS, mRMR, CMIM, ReliefF, FCBF, PGVNS and SVM-RFE, on eleven public datasets. The experiment results showed the superiority of IG-RFE in accuracy, sensitivity, specificity and stability. Hence, integrating feature individual discriminative ability and the interaction among features could better evaluate feature importance in biological data analysis.


Which came first: the readiness or the change? Longitudinal relationships between readiness to change and drinking among college drinkers.
Although readiness to change (RTC) is cited as a key mechanism underlying drinking behavior change, empirical evidence supporting RTC as a predictor of college drinking has been mixed. Considering methodological limitations of previous studies, the current aim was to conduct a more comprehensive test of longitudinal relationships between readiness to change and college drinking. In this correlational, longitudinal study, we used a series of cross-lagged path analyses to test associations between RTC and college drinking outcomes over a 2-year period. Data collection was conducted via online surveys on a university campus in the US Pacific Northwest. Participants (n = 818; 58% women) were college students who reported at least one heavy-drinking episode in the past month and participated in a randomized controlled trial of personalized normative feedback interventions. Drinking quantity-frequency items and the Rutgers Alcohol Problem Index assessed drinking outcomes. The Readiness to Change Questionnaire assessed RTC. For drinking-related problems, the best-fitting model included cross-lagged paths between RTC and subsequent drinking-related problems. For drinking quantity-frequency, best-fitting models also included the cross-lagged paths between drinking quantity-frequency and subsequent RTC. Higher RTC almost uniformly predicted higher subsequent levels of drinking and greater experience of drinking-related problems, and drinking quantity-frequency variables were primarily positive predictors of subsequent RTC. Contrary to previous assumptions, 'the Readiness to Change Questionnaire' does not appear to be predictive of lower levels of subsequent drinking.


Lymph node yield in the initial central neck dissection (CND) associated with the risk of recurrence in papillary thyroid cancer: A reoperative CND cohort study.
To evaluate the relationship between lymph node yield (LNY) from the initial central neck dissection (CND) and the risk of recurrence in patients undergoing reoperative CND for papillary thyroid cancer (PTC). We reviewed clinical data from all patients with pathologically proven PTC who underwent central neck and/or lateral neck dissection reoperations at Nanfang Hospital between 2012 and 2020. Patient demographics, tumor characteristics, clinical data and follow-up information were obtained. In the initial CND, the total number of lymph nodes removed (LNY), total positive nodes removed, and the percentage of positive lymph nodes to the number of lymph nodes removed (PLN%) were determined. A total of 162 patients were included in the study, with a median follow-up of 44 months. 62 had central neck disease recurrence. The optimal LNY and PLN% cut-off values for recurrence were 11 and 65%, respectively. Group 2 (LNY ≥ 11, PLN% < 65%) showed a significantly higher RFS rate than group 1 (LNY < 11 and PLN% < 65%; P < 0.001), group 3 (LNY < 11, PLN% ≥ 65%; P < 0.001), and group 4 (LNY ≥ 11, PLN% ≥ 65%; P = 0.038). Furthermore, group 4 had a higher RFS rate than group 1 (P = 0.008) and group 3 (P = 0.001). Multivariate analysis revealed that LNY < 11 in the central neck was an independent risk factor for recurrence/persistence in the initial surgery (P < 0.001). Higher LNY in central and neck dissections is associated with lower papillary thyroid cancer recurrence rates, which was confirmed by a reoperative CND procedure. To minimize the risk of recurrence and the need for secondary therapy, surgeons should perform compartment-oriented CNDs when indicated.


Muscle differentiation induced by p53 signaling pathway-related genes in myostatin-knockout quail myoblasts.
The myostatin (MSTN) gene is of interest in the livestock industry because mutations in this gene are closely related to growth performance and muscle differentiation. Thus, in this study, we established MSTN knockout (KO) quail myoblasts (QM7) and investigated the regulatory pathway of the myogenic differentiation process. We used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 to generate MSTN KO QM7 cells and subsequently isolated a single cell-derived MSTN KO QM7 subline with 10- and 16-nucleotide deletions that induced translational frameshift mutations. The differentiation capacity and proliferation rate of MSTN KO QM7 cells were enhanced. We conducted next-generation-sequencing (NGS) analysis to compare the global gene expression profiles of wild-type (WT) QM7 and MSTN KO QM7 cells. Intriguingly, NGS expression profiles showed different expression patterns of p21 and p53 in MSTN KO QM7 cells. Moreover, we identified downregulated expression patterns of leukemia inhibitory factor and DNA Damage Inducible Transcript 4, which are genes in the p53 signaling pathway. Using quantitative RT-PCR (qRT-PCR) analysis and western blotting, we concluded that p53-related genes promote the cell cycle by upregulating p21 and enhancing muscle differentiation in MSTN KO QM7 cells. These results could be applied to improve economic traits in commercial poultry by regulating MSTN-related networks.


Highly Ecofriendly Inorganic Pesticide Based on TiO2 Incorporated with Nano-Carbon Composites for Phytophthora palmivora Fungus Disinfection.
Crop destruction organisms are an essential factor hindering cocoa plants' production yield. It is the biggest problem for cocoa farmers to resolve and reduce the impact of the P. palmivora fungus on cocoa pods. Herein, this study presents the optimization of inorganic pesticides based on nano-carbon self-doped TiO2 (C/TiO2) nanocomposites capable of disinfecting broad-spectrum P. palmivora microorganisms for the practical application of photodisinfection technology. C/TiO2 nanocomposite-based inorganic pesticide has been prepared by sol-gel method to produce nanospray and planted in media containing P. palmivora fungus. To identify the various composition of the C/TiO2 nanospray, they were evaluated by FTIR spectroscopy to observe the functional groups of the nano-carbon and TiO2, which clearly contained -OH (3446-3448 cm-1), C≡C (2366-2370 cm-1), C=O (1797-1799 cm-1), C-H (1425 cm-1), C-O (1163-1203 cm-1), C-H (875-877 cm-1), and Ti-O (875-877 cm-1) groups. Some researchers have reported that nano-carbon significantly changes the band gap energy of TiO2 under visible light and can also be active under dark conditions. This statement is relevant to our experimental results that 0.3% C/TiO2 nanocomposites can inhibit the fungus P. palmivora with a percentage inhibition value of 72.7%. However, the high-performance efficiency proved strong when subjected to visible light irradiation with an inhibition value of 98.6%. Our results indicate that C/TiO2 nanocomposites have great potential in agricultural plant pathogen disinfection. The online version contains supplementary material available at 10.1007/s12088-023-01076-7.


CD74 as a regulator of transcription in normal B cells.
CD74 is receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD) that serves as a transcriptional regulator in chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the transcriptional and regulatory function of CD74-ICD in normal B cells. We show that following activation, CD74-ICD forms a complex in the cytosol with transcription factors, like PAX5, and binds the chromatin at a significantly higher number of sites compared with its binding in CLL cells. The expression of a major portion of these bound genes is shut down in the malignant cells. The CD74-ICD:PAX5 complex binds the promoter areas of a tumor-suppressor gene, DMTF1, and downregulates its expression through inhibition of transcription. These findings can help identify novel therapeutic pathways that are regulated during oncogenic transformation and are targets for future treatments.


MRSA screening: incidence and maternal postpartum outcomes in an obstetric population at a tertiary care center.
To assess the incidence of MRSA positive patients in pregnancy, as well as the postpartum outcomes in MRSA positive patients. This is a retrospective cohort study of women who underwent universal MRSA universal at a tertiary medical center. A MRSA swab was routinely collected as part of the patient's prenatal care at 35-37 weeks gestation or on admission to labor and delivery. Demographic information and decolonization antibiotics were collected by electronic medical record review, using ICD-9 codes. Outcome data were collected, including mode of delivery, hospital length of stay, endometritis, wound cellulitis, and wound infection. p < 0.05 was considered significant. A univariate logistic regression and a multivariable binary logistic regression model were used to analyze the strength of association between outcomes and MRSA status. Statistical analysis was performed with SAS, version 9.4. The incidence of MRSA during the 4 year study period was 1.9% (82 MRSA positive out of 4369 total patients). 90.2% (74/82) of MRSA positive patients received decolonization antibiotics. No difference was noted in mode of delivery. Logistic regression failed to identify any significant differences in other relevant outcomes for MRSA positive women including endometritis 1.1 (0.1-17.5) [positive 0, versus negative 0.6% (n = 24)], wound cellulitis 5.9 (0.4-82.1) positive 0, versus negative 0.1% (Gorwitz et al. in J Infect Dis 197:1226-1234, 2008) and wound infection 3.3 (0.6-16.9) [positive 1.2%, versus negative 0.5% ( in Am J Infect Control 32:470-85, 2004)] when compared to MRSA negative women. When universal MRSA screening was performed at an academic tertiary care center, the overall incidence of MRSA was low. MRSA positive and subsequently decolinzed patients did not have any identified increase in postpartum infectious morbidity, as compared to MRSA negative patients.


Acute lymphoblastic leukemia in childhood.
This article reviews those factors that have been responsible for progress in the past, describes current biologic and therapeutic approaches to ALL, and discusses those unresolved treatment issues that pose the major challenge for the future.


AI/LEARN: an interactive videodisk system for teaching medical concepts and reasoning.
This paper describes AI/LEARN, an educational videodisk system designed to teach clinical observational skills and reasoning in medicine. The AI/LEARN system uses a learning conditions approach to teaching. To teach visual concepts, we use the principle of exemplar/nonexemplar pairs and immediate feedback. To teach If-Then problem solving we use the format of minicases with delayed feedback. The software to operate the system has been custom developed and is domain independent. The result is a prototype of a new authoring package for videodisk teaching which operates on IBM compatible microcomputers. The medical domain selected for this prototype system was rheumatic diseases; the knowledge used to teach reasoning skills is derived from the knowledge base of an expert system: AI/RHEUM.


Complication rates of colonoscopy in an Australian teaching hospital environment.
Quality assurance is an important part of health-care delivery. With the high level of awareness relating to adverse events from medical care, demonstration of a high standard of practice in gastroenterology is desirable. To determine the incidence of significant complications or death within 30 days of an outpatient colonoscopy, and confirm that these are in keeping with international standards. A retrospective audit of linked endoscopy and other hospital databases and selected medical records was carried out, based on reports of 30,463 colonoscopies performed between 5 September 1989 and 31 December 1999 in the three Western Australian public teaching hospitals. A total of 23,508 colonoscopies was performed on an outpatient basis between 5 September 1989 and 31 December 1999. Post-procedural complications identified (and incidence) were: bleeding episodes 49 (0.21%), colonic perforation 23 (0.1%), abdominal pain 22 (0.09%), and others 19 (0.08%). A total of 196 patients died within 30 days of undergoing colonoscopy (0.83%), although only three deaths were attributable to the procedure itself (incidence 0.01%). Two were inpatients at the time of the procedure (outpatient mortality rate 0.004%). The combined incidence of bleeding and perforation was not significantly different between consultant endoscopists and unassisted trainees (incidence 0.21% vs 0.20%, P=0.98). The incidence of bleeding and perforation is similar to other reported series and reflects procedures performed by personnel with a wide range of endoscopic experience. The incidence of complications was not greater for trainees compared with consultant endoscopists. All bleeding episodes and the majority of perforations were associated with a therapeutic intervention. Diagnostic colonoscopy in particular is a very safe procedure.


Psychological factors in gastroesophageal reflux disease measured by scl-90-R questionnaire.
An association between psychological factors and gastroesophageal reflux disease has been recognized. Psychological distress can influence the outcomes of the disease. To determine the existence of psychological factors in our gastroesophageal reflux disease sample, as well as determine their influence on the outcome of the disease and treatment response. A cross-sectional study was performed from February 2006 to December 2007. Patients referred to gastrointestinal specialists who reported symptoms of gastroesophageal reflux were asked to fill out the SCL-90-R questionnaire. All underwent endoscopy and pH-metry studies. Fifty-five patients with gastroesophageal reflux disease were analyzed. Subjects with reflux symptoms had higher scores compared to healthy controls on sommatization, obsessiveness, interpersonal sensitivity, being phobic, being psychotic, and the global index (P < 0.05). Patients with high frequency of symptoms and long duration of disease have increased psychological distress. There was no relationship among pH-metry results, endoscopy findings, and SCL-90-R scores. Psychosocial factors can predispose to gastroesophageal reflux disease. The SCL-90-R questionnaire can be useful in investigating psychological factors in those patients with unsuccessful outcome of the symptoms despite correct management.


Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1.
Glycogen synthase kinase-3 beta (GSK-3beta) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3beta in some cell types. The role of GSK-3beta in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3beta in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3 beta signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3beta acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3beta (Ad GSK-3beta S9A) repressed these hypertrophic effects of IGF-1. GSK-3beta may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1.


Outside the Black Box: Re-assessing Pediatric Antidepressant Prescription.
The purpose of this review is to assess whether evidence supports a favorable risk/benefit profile for pediatric antidepressant use and reconsideration of the black box. The review examines studies post-black box purporting to show declines in pediatric antidepressant use and rising youth suicide, summarizes evidence for efficacy and safety of pediatric antidepressants, and discusses irregularities in recent meta-analyses of fluoxetine for youth. Pediatric antidepressant prescription did not significantly decline post-black box and youth suicide has risen only in recent years. Recent meta-analyses fail to undermine evidence that antidepressants are associated with increased risk of suicidality in youth. First line prescription of antidepressants for youth is not advisable. The black box and international warnings on pediatric use of antidepressants are warranted. Wider availability of psychosocial options for depressed youth is recommended.


Evaluation of Connecticut medical providers' concordance with 2017 IDSA/SHEA Clostridioides difficile treatment guidelines in New Haven County, 2018-2019.
To assess Connecticut medical providers' concordance (2018-2019) with the 2017 Clostridioides difficile infection (CDI) treatment update by the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). The effect of guideline concordance on CDI recurrence risk was also assessed. Prospective, population-based study. New Haven County, Connecticut, from January 1, 2017, to December 31, 2019. CDI incident case (no positive tests in the prior 8 weeks), not limited by care setting. Using data from the Emerging Infections Program's CDI surveillance, severity and concordance were defined. Presence of megacolon and/or ileus defined fulminant disease; absence defined nonsevere/severe disease. Using 2017 treatment as baseline, 2018-2019 concordance was defined as receiving the recommended first-line antibiotic (ie, vancomycin or fidaxomicin for adult patients, vancomycin or metronidazole for pediatric patients) for exactly 10 days. For all analyses, significance was P < .05. Among 990 cases, concordance increased from 24.8% in 2018 to 37.0% in 2019. First-line antibiotic concordance increased from 61.2% in 2018 to 79.9% in 2019. Recurrence risk was significantly associated with patients aged ≥65 years and was highest for those aged 75-84 years, but this factor was not significantly associated with concordance. From 2018 through 2019, CDI treatment in New Haven County increasingly was concordant with the 2017 treatment update but remained low in 2019. Although concordance with treatment guidelines did not affect recurrence risk, close attention should be paid by medical providers to patients aged ≥65 years, specifically those aged 75-84 years because they are at an increased risk for recurrence.


Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas.
The level of genomic amplification of the human telomerase gene TERC, which maps to chromosome band 3q26, was determined in primary cervical adenocarcinomas. Interphase nuclei prepared from archival material of 12 primary cervical adenocarcinomas, eight of which were human papillomavirus positive, were hybridised with a triple colour probe set specific for centromeres of chromosomes 3 and 7 and the TERC gene. We observed high proportions of nuclei with increased absolute copy numbers for TERC in all tumours (mean 3.3; range 2.3-5.2). Amplification of the human telomerase gene TERC is a consistent aberration in cervical adenocarcinomas. Therefore, application of our probe set may provide an objective genetic test for the assessment of glandular cells in Pap smears and hence for the diagnosis of cervical adenocarcinomas.


A 5-year recurrence-free survivor with over ten colorectal liver metastases undergoing FOLFOX plus bevacizumab followed by two-stage hepatectomy.
A 62-year-old male was admitted because of lower left abdominal pain and diarrhea. The patient was diagnosed with rectal cancer and multiple liver metastases. First, the laparoscopic Hartmann operation with a D3 lymph node dissection was performed. After five cycles of folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and bevacizumab, and one additional FOLFOX, the tumor markers dramatically decreased; with carcinoembryonic antigen levels ranging from 1096.3 to 7.6 ng/ml and carbohydrate antigen 19-9 levels ranging from 3248.0 to 42.1 U/ml. Computed tomography showed a bilateral 14 colorectal liver metastases which indicated stable disease by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria and optimal morphologic response. A two-stage hepatectomy was performed to complete a curative resection because of the insufficient remnant liver volume. Five partial hepatic resections in the left liver and the right portal vein ligation were performed during the first operation. Thirty-four days later, a right hepatectomy was successfully performed. Pathologically, there was tumor necrosis in 90 percent of the area of the metastasized liver, and viable cells were detected in only a marginal part of the liver. The patient had an uneventful postoperative course and was discharged fifteen days after the second operation. Uracil-tegafur plus leucovorin was administered for 6 months as an adjuvant chemotherapy treatment. The patient is currently alive and has remained disease-free for more than 5 years. In conclusion, an ideal combination of perioperative chemotherapy and curative resection may provide a chance of long-term survival without recurrence of disease for selected patients with more than ten bilateral colorectal liver metastases.


Radiographic study on the pattern of wrist joint destruction in rheumatoid arthritis.
When planning therapy for rheumatoid arthritis (RA) in the wrist joint, knowing the pattern of joint destruction is important. There were a few studies using the Larsen and modified Larsen method to evaluate RA wrist joint destruction. However, these methods are inadequate for thoroughly assessing the severity of joint destruction because joint bone erosion and joint space narrowing could not be evaluated individually in these methods. To clarify the pattern of RA wrist joint destruction in the different zones of the wrist, we conducted a large-scale radiographic study. We modified the van der Heijde/Sharp method to assess radiographic images. Subjects were 191 RA patients (22 men and 169 women; mean age 57.0 years) who were examined at our center between 2001 and 2003 and underwent plain X-ray of both wrist joints (n = 382). Using X-ray images of the wrist joint, classification was performed based on the severity of wrist joint surface bone erosion and joint space narrowing at different zones, and the results were statistically analyzed. The results showed that joint space narrowing in the midcarpal joint (MCJ) advanced faster than in the radiocarpal joint (RCJ). Conversely, bone erosion in the RCJ advanced faster than in the MCJ. In X-ray diagnosis of RA wrist joint disorders, knowing the pattern of destruction is useful for assessing the presence or absence of early joint destruction and in planning therapy.


The pre-emptive analgesic effect of intra-articular bupivacaine in arthroscopic knee surgery.
The purpose of this study was to determine whether intra-articular injection of bupivacaine prior to surgery provided better pain control after arthroscopic meniscectomy as compared with post-operative administration of bupivacaine. Forty patients of American Society of Anesthesiologists (ASA) class I or II undergoing arthroscopic meniscectomy were assigned in a randomized, double-blinded manner into two groups: Group I received 20 ml of 2.5 mg/ml bupivacaine without epinephrine 30 min before skin incision and 20 ml of saline immediately after skin closure. Group II received identical injections in reverse order. All patients received total intravenous anesthesia. Post-operative pain scores were evaluated at 1, 2, 4, 6, 8, 12 and 24 h at rest and movement of the knee, using a 10-cm visual analog scale (VAS). The time to first analgesic use and 24-h analgesic consumption were recorded. Pain scores were lower in Group I compared with Group II at 1, 2, 4 and 6 h at rest and on movement (P < 0.05). The time to first analgesic use was longer in Group I, but there was no statistically significant difference in 24-h analgesic consumption. Intra-articular bupivacaine administered before surgery provided a statistically significant reduction in post-operative pain scores compared with post-operative bupivacaine administration.


The transcription factor masculinizer in sexual differentiation and achieved full functional sex reversal in prawn.
Some Zinc finger (ZnF) proteins are required for masculinization in silkworms. In the present study, a masculinizer gene (Mr-Masc) with multi-tissue expression is identified in the freshwater prawn Macrobrachium rosenbergii. The Mr-Masc is clustered into a separate branch with ZnF proteins from decapoda by phylogenetic tree analysis. Moreover, Mr-Masc silencing in male postlarvae prawn results in functional sex reversal females known as neo-females, which are applied to all-male monosex offspring breeding. This manipulation has been significant in sexually dimorphic cultured species. In addition, several significantly expressed transcripts are enriched and the effects of crucial signal pathways are focused through the comparative transcriptomic analysis in Mr-Masc gene knockdown. The significantly differentially expressed epidermal growth factor, upregulated low-density lipoprotein receptor, flotillin, and sex-lethal unigenes, downregulated heat shock proteins and forkhead box homologs are focused. The finding offers an innovative perspective on Masc proteins' evolution and physiological function.


Epidemiology of Trichinella infection in wild boar from Spain and its impact on human health during the period 2006-2019.
Trichinellosis is a notifiable zoonotic disease caused by parasitic nematode larvae belonging to the genus Trichinella. Domestic pig and wild boar are important hosts within the natural cycle of T. spiralis, the last one being an animal whose populations have experienced an important growth. Therefore, this paper studies the prevalence of Trichinella infection in wild boar in Spain, as well as its relation with hunting and its impact on public health during the period 2006-2019. For this purpose, different sources of information were consulted and analyzed depending on the autonomous communities of Spain and years. During the fourteen years of study, the number of wild boars hunted and the number of cases of Trichinella infection in them increased (from 172 cases in 2006 to 421 in 2019), although prevalence values remained low as the number of animals analyzed also increased. On the other hand, trichinellosis in humans tended to decrease (from a peak of 107 cases in 2007 to 11 cases in 2019). Nevertheless, the numbers of both wild boars and humans infected with Trichinella in Spain are among the highest in Europe, and this emphasizes the importance of food safety, sanitary controls of game meat and citizen awareness campaigns, which prevent the spread of Trichinella through the human population.


The laterally varying ultrasonic velocity in the dentin of human teeth.
There is no quantitative description available that numerically relates any acoustic parameter pattern or the local elastic behaviour to any standardized geometrical positions within human teeth. However, the speed of ultrasound at 20MHz varies in different parts of teeth. Great differences occur between the values attributed to longitudinal waves that propagate in the three mineralized human hard tissues at identical relative tooth width portions [John, C., 2004. The corono-apically varying ultrasonic velocity in human hard dental tissues. Journal of the Acoustical Society of America 116, 545-556]. The aim of this work was to investigate the distribution of the longitudinal ultrasound velocity (LUV) at distinct relative tooth width portions and at a height level of 8mm relative to the coronal reference. Individual tooth widths w were accounted for, and a standardized, dimensionless radial distances variable X=|x/w-0.5| was utilized to express the radial position of measurements in a unified way. The observed lateral increase in LUV of 21 specimens along X was approximated. A Padé shape function predicts the lower contour of the envelope curve of all the individual LUV distributions. Individual residuals and coefficients are provided for LUV=a+b.ln(X).X.X, where a and b represent individual intercepts and slope factors (e.g. a=3206 m/s and b=-4184 m/s), respectively.


Tetraethylorthosilicate as molecular precursor to the formation of amorphous silica networks. A DFT-SCRF study of the base catalyzed hydrolysis.
Quantum chemical calculations using density functional theory have been carried out to investigate two chemical pathways for the last step of the hydrolysis of tetraethylorthosilicate (TEOS) in basic catalyzed environment. The two models that are introduced in this study depend on the number of water molecules involved at the base catalyzed hydrolysis. Solution equilibrium geometries of the molecules involved in the transition states, reactants and product complexes of the two chemical pathways were fully optimized at B3LYP level of theory with the standard 6-31+G(d) basis set, modeling solvent effects using a polarizable continuum solvation model (PCM). Both models predict relative low activation energies. However, the model with two water molecules seems to be more adequate to describe the basic hydrolysis. A natural bond orbital (NBO) analysis seems to show that the proton transfer from water to ethoxy group would occur through a large hyperconjugative interaction, LP(O) → σ*(O-H), which is related to the nonbonding oxygen lone pair orbital from ethoxy group with the vicinal σ*(O-H) anti bonding orbital O-H of a water molecule.


The statistical power of genome-wide association studies for threshold traits with different frequencies of causal variants.
This study aimed to investigate the effects of incidence rate, heritability, and polygenic variance on the statistical power of genome-wide association studies (GWAS) for threshold traits. Different incidence rates of threshold trait (1, 3, 5, 10, 25, 40, 50, 60, 75 and 90%), heritability (10 and 25%), and polygenic variance ratio (0 and 25%) were simulated separately for common (MAF ≥ 0.05), low-frequency (0.05 > MAF ≥ 0.01), and rare (MAF < 0.01) variants. Association studies were performed by logistic and linear mixed models. The highest statistical powers were observed in common and low-frequency variants with an incidence of 25-50% and 10-40%, respectively, but for rare variants, the highest statistical power was observed at low incidence. For all causal variant frequencies, the estimated heritability decline with an increase in incidence rate. We found high statistical power for traits with high heritability. In contrast, those with a high polygenic variance ratio have lower statistical power to detect common causal variants using a linear mixed model. These results demonstrate that the incidence rate of threshold traits, heritability, and polygenic variance may affect the statistical power of GWAS. Therefore, it is recommended that the effect of incidence rate, heritability, and polygenic variance be considered in designing GWAS for threshold traits.


Morphometric characteristics of terminal villi of the placenta in pre-eclampsia.
Comparative morphological study of the placentas from women suffering from pre-eclampsia was carried out. Morphometric studies of histological preparations showed shrinkage and low vascularization of the placental terminal villi determining the development of hypoxia.


[The clinical outcome of proximal fibular osteosarcoma with en-bloc resection].
To evaluate the local recurrence and 5-year survival of proximal fibular osteosarcoma. From October 1997 to July 2005, 12 patients with proximal fibular osteosarcoma were treated. There were 9 males and 3 females. The mean age at diagnosis was 16 (9-23) years old. Histopathological diagnosis were obtained by trut-cut biopsy, Enneking surgical stages of 12 lesions were as follows: 11 grade II B and 1 grade III. Induction chemotherapy was applied to all patients except one who left the hospital after the biopsy. Of 11 patients, 8 were performed Malawer type I resection, and 3 type II. All patients continued to get postoperative chemotherapy. Regular follow-up was applied. Only 1 patient was found local recurrence one year after operation and received re-resection, the others did not. Four patients died of lung metastases, including the one who did not get treated, one stage III and two II B patients. The range of follow up was 6 to 117 months. The evaluated 5 year disease-free survival of 11 patients who got treated was 72.7% by using Kaplan Meier survival analysis. The local recurrence is low, and 5 year disease-free survival is acceptable, in accordance with present point that marginal resection may not impact survival for fibular osteosarcoma. No knee instability is found in this group after great care is taken for proper reconstruction of lateral collateral ligament and reinsertion of biceps femoris tendon on the lateral condyle of tibia.


E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-β1/Smad pathway.
Liver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. This study is firstly performed to explore the chemical constituents of ES extract together with its anti-hepatic fibrosis effect and potential mechanism on CCl4 treated mice. The chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. UHPLCHRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-α, IL-1β) expressions were inhibited after ESE administration via suppressing NF-κB pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-β1, Smad2, α-SMA, and collagens Ⅰ and III proteins, thereby effectively alleviate the liver fibrosis. This study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-κB pathway and reducing deposition of liver fibrosis via suppressing TGF-β/Smad pathway.


Prognosis of HIV infected sub-Saharan patients on renal replacement therapy (RRT) in Brussels, Belgium: a single centre retrospective pilot study and review of the literature.
Few data exist documenting the survival experience of immigrated sub-Saharan patients infected by the human immunodeficiency virus (HIV) on renal replacement therapy (RRT). This retrospective single centre pilot study includes 105 consecutive patients of sub-Saharan origin who started RRT in our unit, between January 1986 and April 2010. The aim was to analyse the characteristics and the survival rate on RRT of these patients. Out of 105 patients 81/105 (77%) were HIV-negative and 24/105(23%) were HIV-positive. HIV-positive patients were younger than HIV-negative patients and they were more often treated with peritoneal dialysis (PD) (21/24) than with haemodialysis (HD). Dialysis peritonitis was equally distributed between HIV-positive and HIV-negative patients. Because of opportunistic infections, duration of hospitalisation was longer for HIV-positive than for HIV-negative patients. In PD-treated patients, the number of hospitalisations tended to be greater in patients who experienced at least one peritonitis episode and the duration of hospitalisation also tended to be longer. The survival rate was better in patients younger than 50 years and in patients on HD, but was similar for both positive and negative HIV patients. To the best of our knowledge, these are the first data concerning patients who have emigrated from sub-Saharan Africa to Belgium, and who are on RTT. Their survival rate is better if they are younger than 50 years and on HD. As the majority of HIV patients were treated by PD in our center, a conclusion regarding survival on different dialysis modalities is not possible for this group of patients. Survival rates were similar for HIV-positive and HIV-negative patients despite longer duration of hospisalization for HIV-positive patients.


Period-2: a tumor suppressor gene in breast cancer.
Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels.


Synthesis and structure-activity relationships of novel anti-hepatitis C agents: N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives.
Several 6- and 7-monosubstituted N3,5'-cyclo-4-(beta-d-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives as well as the 5-thiono analogue were synthesized, providing structure-anti-hepatitis C virus (HCV) activity relationships for the series. Among the compounds synthesized, the 6-bromo, 7-methylamino, and 5-thiono analogues exhibited more potent anti-HCV activity in an HCV subgenomic replicon cell based assay (EC90 = 1.9, 7.4, and 10.0 microM, respectively) than the lead compound N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one (EC90 = 79.8 microM).


Caught in a web of trauma: Network analysis of childhood adversity and adult mental ill-health.
Current interventions for adverse childhood experiences have only limited effectiveness. We sought to identify optimal targets for the development of new interventions against adverse childhood experiences (ACE), that is, ACEs that a) are so central in the network of childhood adversity that curbing them is likely to impact other types of adversity, too, and b) are so central to the link of childhood adversity and adult mental ill-health that curbing them is likely to prevent this negative long-term effect from developing. 384 adult psychiatric inpatients. Using the R packages qgraph and IsingFit, we analyzed the ACE network and the common network of ACEs and adult mental disorders. We found two clusters of ACEs: direct interactions with the child and indirect traumatization via adverse circumstances. When controlling for interrelatedness, the associations of sexual abuse with posttraumatic stress disorder and borderline personality disorder were the only direct links between ACEs and adult mental disorders. As neglect and violence against the mother were the most influential ACEs, curbing them is likely to destabilize the whole network of adversity. Thus, neglect and violence against the mother lend themselves as candidate targets for the development of new interventions. As sexual abuse was the only link between childhood adversity and adult mental ill-health, interventions against it seem most likely to keep this negative long-term effect from developing. Further, ideally prospective, research is needed to corroborate these findings.


Corpus callosotomy in children.
All of the reports of corpus callosotomy have been limited by their necessarily retrospective nature, lack of control groups, and failure to quantify seizure frequency and duration before and after the surgery. In addition, interpretation of results has been confusing by inconsistent selection criteria of patients, varying surgical procedures employed, and short duration of follow-up. Nevertheless, this procedure remains a last hope for many children with severe intractable epilepsy and unquestionably assists in the management of many such children. There is a need to evaluate this surgical procedure fully to optimize its utilization further.


Human melatonin response to light at different times of the night.
Normal control subjects were examined on three separate occasions with light of sufficient intensity to suppress nocturnal plasma melatonin concentrations. One hour of light was given at each of the following times: (a) 2100-2200h; (b) midnight to 0100h; (c) 0400-0500h. Melatonin synthesis was just becoming apparent at 2100h. There was significant suppression of melatonin by light when given at midnight-0100h and 0400-0500h, but not when light was given at 2100-2200h. In each case following light, melatonin synthesis was shown to resume, even after light applied in the second half of the dark period (0400-0500h). A second experiment was undertaken to examine a possible "rebound" in melatonin levels following light given at 2100-2200h. Six further control subjects were exposed to light at this time, and plasma melatonin levels were measured until 0400h. No rebound in melatonin concentrations was observed. These results are compared with other studies of melatonin response to evening light exposure.


A novel PAX6 nonsense mutation identified in an Iranian family with various eye anomalies.
The aim of this study was to detect the genetic defects in a large pedigree of affected individuals with various phenotypes of ocular anomalies including partial aniridia, congenital cataract, and nystagmus. The entire coding region of paired box gene 6 (PAX6) was amplified by polymerase chain reaction (PCR), sequenced, and compared with a GenBank database. A novel mutation (c.1170 C > T; p.Gln297X) was found in the proband and all affected members. This nonsense mutation leads to PAX6 protein truncation. Our findings suggest that this novel mutation is most likely responsible for the pathogenesis of the congenital aniridia, cataract, and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation of PAX6 gene in a kindred pedigree with various ocular abnormalities.


Effect of glucocorticoids on contractile apparatus of rat skeletal muscle.
Skeletal muscles which have a high oxidative potential are less sensitive to the catabolic action of dexamethasone. In fast-twitch white muscles, where the oxidative capacity is low, the alkaline proteinase activity as well as the rise in the number of lysosomes was more pronounced. It seems that the glucocorticoid-caused myopathy is a result of elevated degradation of contractile proteins. This process of degradation of contractile proteins begins in the myosine filaments and then spreads to the thin filaments and the z-line.


The animal's dignity in Swiss Animal Welfare Legislation--challenges and opportunities.
The introduction of the animal's dignity as a concern in animal welfare legislation in Switzerland is unique worldwide. Naturally, this measure has raised hopes and fears in those concerned with animal welfare and animal use. For the past several years, a lively debate has focused on the question of whether the addition is merely a declaration of intent or an explicit demand with, possibly, a profound impact on everyday practice. What the implications may be in the latter case is not clear. In the area of research, it has yet to be seen how this concept may be incorporated feasibly, for example, into the harm-benefit analysis, which is the prerequisite for the approval of an animal experiment. It is foreseeable, therefore, that this addition might have direct implications on research. Unfortunately, in the legislative text, there are some inconsistencies in wording, at least in the German version, that complicate interpretation. This article provides a short overview of some aspects of the controversy, which is far from settled at this time. The commentary will be restricted to the situation of experimental animals in Switzerland.


[Clinical and microbiological study of compound of light yellow Sophora root collutory on treatment of oral lichen planus].
To evaluate the effect of compound light yellow Sophora root collutory on oral erosive lichen planus and analyze the salivary microbial contents and proportion. 30 patients with oral erosive lichen planus were chosen and treated with compound light yellow Sophora root collutory. Pain index and clinical symptoms were observed, the changes of quantity and proportion of salivary bacteria were investigated before and after taking drugs. SAS6.12 software package was used for statistical analysis. The extravasate and congest of the erosive mucous membrane were relieved. The pain caused by erosion were significantly relieved after taking the drugs. The quantity of oral Staphylococcus was significantly decreased after taking the drugs. Oral Staphylococcus can be inhibited by light yellow Sophora root collutory. The use of compound light yellow Sophora root collutory is one of the safe and effective local therapies on oral lichen planus.


Health-related quality-of-life among survivors of acute kidney injury in the intensive care unit: a systematic review.
To summarize evidence on long-term health-related quality-of-life (HRQL) among survivors of acute kidney injury (AKI) in the intensive care unit (ICU). We performed a comprehensive search of the literature for studies reporting original data describing HRQL utilizing validated instruments. Search, study selection and data abstraction were performed in duplicate. Study quality was appraised. Due to study heterogeneity, data are primarily summarized qualitatively. Our search yielded 2193 articles of which 18 were selected for detailed analysis. The quality of these 18 studies was generally good. Numerous HRQL instruments were utilized, and assessment occurred at variable follow-up duration (range 2 months to 14.5 years). HRQL among AKI survivors was reduced when compared to age/sex-matched populations. HRQL among survivors with and without AKI was generally described as similar beyond 6 months. Physical component domains were consistently more impaired than mental component domains. Survivors had considerable limitations in activities of daily living, implying newly acquired disability, with few returning to work. Despite diminished HRQL, patients' HRQL was generally perceived as satisfactory, and the majority would receive similar treatment again, including renal replacement therapy in the ICU, if necessary. Among survivors of critical illness complicated by AKI, HRQL was impaired when referenced to population norms, but it was not significantly different from that of survivors without AKI. Physical limitations and disabilities were more commonly exhibited by AKI patients. Importantly, the impaired HRQL was generally perceived as acceptable to patients, most of whom expressed willingness to undergo similar treatment in the future.


Effect of metal ions on the fluorescence of leucine aminopeptidase and its dansyl-peptide substrates.
The effect of Cu(II), Ni(II), Zn(II), Mg(II), and Mn(II) on the fluorescence of porcine kidney cytosol leucine aminopeptidase and three of its dansyl(Dns) peptide substrates, Leu-Gly-NHNH-Dns, Leu-Gly-NH(CH2)2NH-Dns, and Leu-Gly-NH(CH2)6NH-Dns, has been investigated. These five metal ions were chosen for study because each binds to the regulatory metal binding site of leucine aminopeptidase. Since the binding is relatively weak, kinetic studies of the different metalloderivatives of the enzyme are normally carried out in the presence of large molar excesses of these metal ions that can potentially affect both the enzyme and substrate. The fluorescence of all of the dansyl-peptides, as well as several other dansyl species, is quenched by Ni(II) and Cu(II), but not by Mg(II), Mn(II), or Zn(II). The absorption spectra of these dansyl substrates are also perturbed by Ni(II) and Cu(II). The rate at which maximal quenching for some dansyl species is attained after mixing with Ni(II) and Cu(II) is slow and the quenching is reversed on addition of EDTA. These results indicate that the quenching is the result of complex formation between the fluorophores and these metal ions. The association constants for the metal complexes have been determined from Stern-Volmer plots. In addition to complex formation, Ni(II) and Cu(II) cause the degradation of Leu-Gly-NHNH-Dns through a two step mechanism involving loss of dansic acid. Ni(II) and Cu(II) also partially quench the fluorescence of leucine aminopeptidase through contact with its surface accessible Trp residues. These observations indicate that care must be taken in stopped flow fluorescence studies of reactions between this enzyme and its dansyl substrates to avoid adverse effects brought about by Ni(II) and Cu(II).


Acquired resistance to ixodid ticks induced by tick cement antigen.
Antisera from guinea pigs made resistant to infestation with an ixodid tick of east and central Africa, Rhipicephalus appendiculatus, were used to identify the tick antigens they recognized by immunoblotting. Most of the antigens were found in tick salivary glands and in tick attachment cement. Antisera from R. appendiculatus-resistant guinea pigs also recognized some salivary-gland antigens in ticks of other species (R. pulchellus, R. evertsi, Amblyomma variegatum and A. gemma). Antibodies against the most strongly recognized R. appendiculatus antigen, a 20-kDa molecule, were only poorly reactive with similar-sized molecules in the other ticks. A 94-kDa antigen, which appeared to have broader cross-reactivity, was purified from R. appendiculatus attachment cement, and a monospecific rabbit serum was raised against it. This antiserum clearly recognized a molecule of similar molecular weight in R. pulchellus and R. evertsi. Intravenous inoculation of rabbits with the purified molecule elicited delayed-type hypersensitivity to the antigen. The hypersensitive rabbits demonstrated resistance to feeding of R. appendiculatus ticks but slight enhanced feeding of R. pulchellus ticks. These results are discussed with respect to their relevance for artificial induction of tick-feeding resistance.


Fate of phospholipids during aqueous extraction processing of peanut and effect of demulsification treatments on oil-phosphorus-content.
PC (phosphatidylcholine), PE (phosphatidylethanolamine), PI (phosphatidylinositol), and PA (phosphatidic acid) in 9 peanut matrices obtained during the AEP (aqueous extraction processing) of peanut were quantified employing HPLC-ELSD analysis in this study. Phosphorus contents of crude oils obtained from different demulsification treatments were also investigated. Decantation had a larger effect than grinding in terms of phospholipids loss due to alkaline-hydrolysis, indicating this processing step was vital for the manipulation of phospholipids levels remained in oil. Over 80% of initial phospholipids were lost during AEP and only 19.8% of initial phospholipids ended up in cream, skim and sediment phase. 52.55% of the remained phospholipids trapped in cream phase. Just 22.16-32.61 mg/kg phosphorus content could be detected in crude oils, which indicated the separation of phospholipids from the cream phase into aqueous medium. Degumming was not essential in AEP of peanut and the waste generated after demulsification could be a source of phospholipids.


Co-occurrence patterns and environmental factors associated with rapid onset of Microcystis aeruginosa bloom in a tropical coastal lagoon.
The environmental factors contributing to the Microcystis aeruginosa bloom (hereafter referred to as Microcystis bloom) are still debatable as they vary with season and geographic settings. We examined the environmental factors that triggered Microcystis bloom outbreak in India's largest brackish water coastal lagoon, Chilika. The warmer water temperature (25.31-32.48 °C), higher dissolved inorganic nitrogen (DIN) loading (10.15-13.53 μmol L-1), strong P-limitation (N:P ratio 138.47-246.86), higher water transparency (46.62-73.38 cm), and low-salinity (5.45-9.15) exerted a strong positive influence on blooming process. During the bloom outbreak, M. aeruginosa proliferated, replaced diatoms, and constituted 70-88% of the total phytoplankton population. The abundances of M. aeruginosa increased from 0.89 × 104 cells L-1 in September to 1.85 × 104 cells L-1 in November and reduced drastically during bloom collapse (6.22 × 103 cells L-1) by the late November of year 2017. The decrease in M. aeruginosa during bloom collapse was associated with a decline in DIN loading (2.97 μmol L-1) and N:P ratio (73.95). Sentinel-3 OLCI-based satellite monitoring corroborated the field observations showing Cyanophyta Index (CI) > 0.01 in September, indicative of intense bloom and CI < 0.0001 during late November, suggesting bloom collapse. The presence of M. aeruginosa altered the phytoplankton community composition. Furthermore, co-occurrence network indicated that bloom resulted in a less stable community with low diversity, inter-connectedness, and prominence of a negative association between phytoplankton taxa. Variance partitioning analysis revealed that TSM (16.63%), salinity (6.99%), DIN (5.21%), and transparency (5.15%) were the most influential environmental factors controlling the phytoplankton composition. This study provides new insight into the phytoplankton co-occurrences and combination of environmental factors triggering the rapid onset of Microcystis bloom and influencing the phytoplankton composition dynamics of a large coastal lagoon. These findings would be valuable for future bloom forecast modeling and aid in the management of the lagoon.


Guideline Clearinghouse Is Dead. Long Live the Guideline Clearinghouse?
The National Guidelines Clearinghouse might be making a comeback. It's been contracted out to the ECRI Institute, a not-for-profit organization that conducts medical safety research. ECRI plans to have a version of the clearinghouse website up and running anytime soon, with plans for a full relaunch in 2019.


Tetracycline removal using green synthesized bimetallic nZVI-Cu and bentonite supported green nZVI-Cu nanocomposite: A comparative study.
Antibiotics, one of the most abundant contaminants in the natural water systems possess various difficulties to remediate through conventional water treatment methods. Tetracycline (TC) remains one of the most widely used antibiotics for human and veterinary applications because of its broad-spectrum antibacterial activity. In the current study, we have employed nano zero-valent technology-based antibiotic remediation. In a first of its kind work, we applied bimetallic nZVI-Cu nanoparticles synthesized using pomegranate rind extract for remediation. TC removal of 72 ± 0.5% (initial TC concentration 10 mg/L) was obtained with the nZVI-Cu concentration of 750 mg/L at pH 7. To overcome the colloidal instability and enhance TC removal further, the bimetallic nanoparticles were formed in-situ over bentonite. The bentonite supported composite (B/nZVI-Cu) was used to treat TC an initial concentration of 10 mg/L and the results confirmed significant enhancement in removal with a substantially decreased nanoparticle loading. Using only 150 mg/L of B/nZVI-Cu at pH 7, 95 ± 0.05% of TC could be removed. The nanoparticles and the composites were characterized by SEM, FT-IR, and XRD analyses. The removal process was followed by UV-Visible analyses in conjunction with TOC, ORP and LCMS measurements. For treatment using B/nZVI-Cu, the reusability of the composite was established up to three cycles of operation, and the process was validated in the real water systems. Substantially decreased residual toxicity of the composite treated TC solution lends credence to the environmental sustainability of the process.


Determination of the activity of nonspecific monophosphoesterases and nonspecific esterase in the liver of dogs in extrahepatic cholestasis treated surgically and with phenobarbital.
Histochemical researches on livers of 19 dogs were carried out. The dogs suffered from extrahepatic cholestasis which lasted for 28 days and was surgically induced. The dogs were divided into three groups, out of which two were given phenobarbital for 21 or 28 days. In all groups biliary obstruction was removed by surgical operation. It was shown that a combined surgical treatment with the application of phenobarbital has given better results than a surgical treatment alone.


MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy.
Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. • mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.


Reciprocal regulation of preprothyrotropin-releasing hormone (TRH) mRNA in the rat anterior hypothalamus by thyroid hormone: dissociation from TRH concentrations during hypothyroidism.
TRH mRNA has not been quantified concomitantly with TRH itself to examine graded effects of thyroid hormones (TH) upon TRH gene transcriptional regulation and post-transcriptional expression. To examine such TH effects, rats were rendered thyrotoxic with L-T3 (50 micrograms per 100g body weight) or hypothyroid by total thyroidectomy. After decapitation, frozen coronal brain sections were prepared in a matrix for hypothalamic micropunches. PreProTRH mRNA was quantified in punch pools by slot-blot hybridization and densitometry, using a 32P 1.2Kb rat riboprobe (gift of Drs. S. Lee and R. Goodman). T3 toxicosis resulted in parallel reductions in PreProTRH mRNA (-45%) and TRH concentrations determined by RIA (-43%), 1.1 versus 1.9 ng/mg protein, p less than 0.01. Conversely, elevations in PreProTRH mRNA were stimulated by hypothyroidism on Day 14 (+32%). However, TRH concentrations were reduced paradoxically from 2.2 +/- 0.05 ng/mg protein to 0.68 +/- 0.03, p less than 0.01. No changes, in contrast, were identified in whole hypothalamic extracts in either PreProTRH mRNA or TRH after T3 treatment. It is concluded that TH do exert inhibitory effects upon PreProTRH mRNA transcription, and in the specific hypothalamic nucleus concerned with thyroid regulation (PVN). The failure of TRH concentrations to rise concordantly with activated TRH gene transcription in hypothyroidism suggests that TH may exert inhibitory effects upon PreProTRH mRNA translation, in addition to inhibition of TRH gene transcription and TRH secretion.


Clinical, muscle imaging, and genetic characteristics of dystrophinopathies with deep-intronic DMD variants.
Phenotypic heterogeneity within or between families with a same deep-intronic splice-altering variant in the DMD gene has never been systematically analyzed. This study aimed to determine the phenotypic and genetic characteristics of patients with deep-intronic DMD variants. Of 1338 male patients with a suspected dystrophinopathy, 38 were confirmed to have atypical pathogenic DMD variants via our comprehensive genetic testing approach. Of the 38 patients, 30 patients from 22 unrelated families with deep-intronic DMD variants underwent a detailed clinical and imaging assessment. Nineteen different deep-intronic DMD variants were identified in the 30 patients, including 15 with Duchenne muscular dystrophy (DMD), 14 with Becker muscular dystrophy (BMD), and one with X-linked dilated cardiomyopathy. Of the 19 variants, 15 were single-nucleotide variants, 2 were structural variants (SVs), and 2 were pure-intronic large-scale SVs causing aberrant inclusion of other protein-coding genes sequences into the mature DMD transcripts. The trefoil with single fruit sign was observed in 18 patients and the concentric fatty infiltration pattern was observed in 2 patients. Remarkable phenotypic heterogeneity was observed not only in skeletal but also cardiac muscle involvement in 2 families harboring a same deep-intronic variant. Different skeletal muscle involvement between families with a same variant was observed in 4 families. High inter-individual phenotypic heterogeneity was observed within two BMD families and one DMD family. Our study first highlights the variable phenotypic expressivity of deep-intronic DMD variants and demonstrates a new class of deep-intronic DMD variants, i.e., pure-intronic SVs involving other protein-coding genes.


Analysis of molecular mechanisms of ATP synthesis from the standpoint of the principle of electrical neutrality.
Theories of biological energy coupling in oxidative phosphorylation (OX PHOS) and photophosphorylation (PHOTO PHOS) are reviewed and applied to ATP synthesis by an experimental system containing purified ATP synthase reconstituted into liposomes. The theories are critically evaluated from the standpoint of the principle of electrical neutrality. It is shown that the obligatory requirement to maintain overall electroneutrality of bulk aqueous phases imposes strong constraints on possible theories of energy coupling and molecular mechanisms of ATP synthesis. Mitchell's chemiosmotic theory is found to violate the electroneutrality of bulk aqueous phases and is shown to be untenable on these grounds. Purely electroneutral mechanisms or mechanisms where the anion/countercation gradient is dissipated or simply flows through the lipid bilayer are also shown to be inadequate. A dynamically electrogenic but overall electroneutral mode of ion transport postulated by Nath's torsional mechanism of energy transduction and ATP synthesis is shown to be consistent both with the experimental findings and the principle of electrical neutrality. It is concluded that the ATP synthase functions as a proton-dicarboxylic acid anion cotransporter in OX PHOS or PHOTO PHOS. A logical chemical explanation for the selection of dicarboxylic acids as intermediates in OX PHOS and PHOTO PHOS is suggested based on the pioneering classical thermodynamic work of Christensen, Izatt, and Hansen. The nonequilibrium thermodynamic consequences for theories in which the protons originate from water vis-a-vis weak organic acids are compared and contrasted, and several new mechanistic and thermodynamic insights into biological energy transduction by ATP synthase are offered. These considerations make the new theory of energy coupling more complete, and lead to a deeper understanding of the molecular mechanism of ATP synthesis.


Independence of gonadotropin and adrenal androgen secretion.
Five groups of 5 normal adult males have been studied. Group 1 received clomiphene, group 2 received exogenous FSH and group 3 testosterone. These three groups received drugs to stimulate LH and FSH, increase levels of FSH or suppress LH and FSH respectively. Circulating levels of testosterone (T), estrone (E1) and 17-hydroxyprogesterone (17-OHP) were altered while serum concentrations of androstenedione (A), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroids (17-KS) were not. The other two groups of 5 adult males had adrenal androgen levels suppressed or stimulated while receiving dexamethasone or ACTH. Serum 17 OHP, A, DHA and DS levels and urinary 17 KS were affected while gonadotropins were unaltered. Hence, no relationship has been demonstrated between circulating levels of adrenal androgens and gonadotropins.


Conformation and anticancer activity of a novel mannogalactan from the fruiting bodies of Sanghuangporus sanghuang on HepG2 cells.
A novel water-soluble mannogalactan (SSPS1) with an average molecular weight of 2.04 × 104 Da was obtained from the fruiting bodies of the Sanghuangporus sanghuang. It revealed that SSPS1 was composed of d-galactose, d-mannose, l-fucose, 3-O-methylgalactose and d-glucose in a ratio of 6.2:3.9:3.1:2.1:1.0. The structural elucidation of SSPS1 consisted of 1, 6-linked α-D-Galp, 1, 6-linked α-D-Manp and 1, 6-linked 3-O-methyl-α-D-Galp backbone with branching at O-2 of 1, 6-α-D-mannosyl residues by α-L-Fucp and α-D-Glcp units. The conformational parameters suggested that a flexible chain conformation of SSPS1 in solution based on light scattering and atomic force microscopy imaging. Intriguingly, it presented potent anticancer activity on HepG2 cell with Rq and Ra values increased dramatically up to 73.93 nm and 53.92 nm compared with the control. The analysis of flow cytometry indicated SSPS1 could induce the apoptosis of HepG2 cells and arrest them via S phase. Western blot assay further uncovered that apoptosis process was triggered by SSPS1 via a mitochondria-mediated signaling pathway, which was evidenced by an increased ratio of Bax/Bcl-2, the release of cytochrome c and the strong activation of caspase-3 and 9. Taken together, these results suggested that SSPS1 might be applied in functional food as an anticancer agent.


Neuronal control of the ventromedial nucleus from the periventricular nucleus in the hypothalamic slice of the rat.
A neuronal pathway between periventricular nucleus and ventromedial hypothalamus (VMH) was investigated by both anatomical and electrophysiological methods. Horseradish peroxidase (HRP)-labelled clusters were observed in the periventricular nucleus after application of HRP into the VMH. Periventricular nucleus stimulation produced mainly excitation of VMH neurones with a latency of 3 msec. These results suggest that periventricular nucleus sends information in the cerebro-spinal fluid to the VMH.


The Attention-Lapse and Motor Decoupling accounts of SART performance are not mutually exclusive.
There is an ongoing debate about the mechanisms purported to underlie performance in the Sustained-Attention-to-Response Task (SART). Whereas the Attention-Lapse account posits that SART errors result from attentional disengagement, the Motor Decoupling account proposes that SART errors result from failures to inhibit a fast, prepotent motor response, despite adequate attention to the task. That SART performance might be fully accounted for by motor decoupling is problematic for a Attention-Lapse account, and for the use of the SART as an index of attention lapses. To test whether SART performance is in fact fully accounted for by motor decoupling, I examined the relation between SART performance and attention lapses while controlling for motor decoupling. The results were clear: The SART was associated with attention lapses independently of motor decoupling. Thus, the present study suggests that both accounts are correct and that the SART is a valid measure of attention lapses.


Spermatocyte selection during meiosis following mitomycin C treatment in mice.
In mice treated with mitomycin C, elimination of spermatocytes is observed during meiotic division, whereby an increase in number of the eliminated cells is closely related to an increase in the frequency of spermatocytes with chromosome aberrations at M-I.


Sessile bacterium unlocks ability of surface motility through mutualistic interspecies interaction.
In addition to their common planktonic lifestyle, bacteria frequently live in surface-associated habitats. Surface motility is essential for exploring these habitats for food sources. However, many bacteria are found on surfaces, even though they lack features required for migrating along surfaces. How these canonical non-motile bacteria adapt to the environmental fluctuations on surfaces remains unknown. Here, we report a previously unknown surface motility mode of the canonical non-motile bacterium, Dietzia sp. DQ12-45-1b, which is triggered by interaction with a dimorphic prosthecate bacterium, Glycocaulis alkaliphilus 6B-8T. Dietzia cells exhibits 'sliding'-like motility in an area where the strain Glycocaulis cells was pre-colonized with a sufficient density. Our analysis also demonstrates that Dietzia degrade n-alkanes and provide Glycocaulis with the resulting metabolites for survival, which in turn induced directional migration of Dietzia towards nutrient-rich environments. Such interaction-triggered migration was also found between Dietzia and Glycocaulis strains isolated from other habitats, suggesting that this mutualistic relationship ubiquitously occurs in natural environments. In conclusion, we propose a novel model for such a 'win-win' strategy, whereby non-motile bacteria pay metabolites to dimorphic prosthecate bacteria in return for migrating to seek for nutrients, which may represent a common strategy for canonically non-motile bacteria living on a surface.


Discovery and characterization of a cytochalasan biosynthetic cluster from the marine-derived fungus Aspergillus flavipes CNL-338.
Cytochalasans are a large family of well-studied cytotoxic molecules isolated from fungi. Investigation into the organic extract of the marine-derived fungal strain Aspergillus flavipes CNL-338 led to the isolation of seven leucine-containing cytochalasans. Genome mining allowed for the identification of the ffs biosynthetic gene cluster, and genetic inactivation studies verified its involvement in cytochalasan biosynthesis. In addition, comparative analysis of key residues in the binding pocket of core cytochalasan biosynthetic enzymes revealed significant similarities among fungal adenylation domains despite differences in substrate preference. We report the identification of leucine-containing cytochalasans from the marine-derived A. flavipes CNL-338 and the characterization of the ffs biosynthetic cluster as verified by genetic inactivation studies.


Two-Strip Technique to Repair Common Atrioventricular Valve Regurgitation in Single-Ventricle Palliation.
A common atrioventricular valve (CAVV) presents a challenge in single-ventricle palliation (SVP) because of its propensity to leak, with CAVV regurgitation being an important risk factor for repeated operation and mortality. We propose a new technique of CAVV repair in the context of SVP. The method uses the techniques of complete repair of antrioventricular septal defect while maintaining free communication at atrial and ventricular levels necessary for single-ventricle physiology.


Trends in ammonia emissions from light-duty gasoline vehicles in China, 1999-2017.
Ammonia (NH3) emitted from motor vehicles is a by-product of measures taken to reduce emissions of other pollutants (e.g. NOx and CO) and has potentially important environmental impacts. NH3 levels can be impacted by various emission standards. However, there is a lack of investigations of the influences from the implementation of different vehicular emission standards on long-term changes in NH3 emissions. To fill this gap, we estimated the inter-annual NH3 emissions of light-duty gasoline vehicles (LDGVs) under different emission standards (State 0 to State V) from 1999 to 2017 and investigated the emission change characteristics under the rapidly developing Chinese economy. Results showed that the NH3 emissions from LDGVs had a sharp, 42-fold increase (from 1.8Gg to 77.9Gg). However, NH3 emissions per capita have begun to decrease with increases in socioeconomic development, presenting an inverted U-shaped tendency as a function of per capita GDP. Further exploration indicated that the decline in emission factors, as determined by upgrades in emission standards, was the decisive factor in promoting the downward trend in per capita emissions. This suggests that continuously upgrading emission standards has offset the increase in NH3 emissions due to the rapid growth of motor vehicles. Quantitative scenario analysis showed a two-stage impact of emission standards on NH3 emissions: emissions would decrease 77% (48%-90% for different years) if State I and State II were not implemented; while if none of standards were upgraded (State III to State V), NH3 emissions would increase 118% (13%-224% for different years), 2-6 times the impacts from the growth of vehicle population and the decline of vehicle kilometres traveled. The data and findings in this study can provide scientific support for understanding air pollution in urban areas and for formulating further vehicle pollution mitigation measures in China and other countries.


Cytotoxic and antivascular 1-methyl-4-(3-fluoro-4-methoxyphenyl)-5-(halophenyl)-imidazoles.
A series of 1-methyl-4,5-diphenylimidazoles 6 with various patterns of m-halogen substitution at the 5-phenyl ring were tested for cytotoxicity in cancer and nonmalignant cell lines and for their capacity to prevent tube formation in HUVEC cultures. Unlike the monofluoro and difluoro derivatives 6a and 6e, the monobromo and diiodo analogs 6c and 6h were strongly cytotoxic and inhibited the polymerization of tubulin and the tube formation by HUVEC. The dibromo derivative 6g displayed a unique selectivity for KB-3-1 cervix and PC-3 prostate cancer cells. It also inhibited the tube formation by HUVEC and the polymerization of tubulin which is indicative of its potential antiangiogenic activity in solid tumors.


What caregivers like the most (and least) about cognitive behavioral therapy for youth anxiety: A mixed methods approach.
Cognitive behavioral therapy (CBT) is an efficacious therapy for youth anxiety disorders. Caregivers are key stakeholders in youth therapy, and their feedback on treatment can help to inform intervention personalization. This mixed-methods study applied a systematic inductive thematic analysis to identify themes among most- and least-liked CBT features reported by caregivers using open-ended responses on the Client Satisfaction Questionnaire (CSQ-8). The sample included 139 caregivers of youth ages 7-17 (M = 12.21, SD = 3.05; 59% female; 79.1% Caucasian, 5.8% Black, 2.9% Asian, 2.2% Hispanic, 7.9% Multiracial, 2.2% Other) with principal anxiety diagnoses who completed 16-sessions of CBT. CSQ-8 quantitative satisfaction scores (M = 29.18, SD = 3.30; range: 16-32) and survey-based treatment response rates (responders n = 93, 67%) were high. Most-liked treatment features included: coping skills (i.e., exposure, understanding/identifying anxiety, rewards, homework), therapist factors (interpersonal style/skill, relationship, accessibility), caregiver involvement, one-on-one time with a therapist, structure, consistency, and personally tailored treatment. Least-liked treatment features included: questionnaires, logistical barriers, telehealth, need for more sessions, non-anxiety concerns not addressed, insufficient caregiver involvement, and aspects of exposure tasks. Proportional frequencies of most- and least-liked themes differed by treatment responder status (e.g., responders cited exposure and homework as most-liked more frequently).


Consumption of milk and milk products in the population of the Upper Silesian agglomeration inhabitants.
Providing the appropriate amount of nutrients at every stage of life is a key element determining the proper development and functioning of the body. Because of the nutritional value and resulting position of milk and milk products in the daily diet, this study was undertaken to assess the consumption of milk and milk products among the inhabitants of the Upper Silesian agglomeration. The survey covered 600 people, including 339 women (56.5%) and 261 men (43.5%) aged 18-78 years. To assess the consumption of milk and milk products, as a research tool an original survey with the closed-ended and open-ended questions was used. The questions concerned the characteristics of the surveyed group and various aspects of the consumption of milk and milk products. The results obtained were subjected to statistical analysis using the Statistica 10.0 program with a chi-square test for quality features. The level of consumption of milk and milk products among the Upper Silesian agglomeration inhabitants is insufficient in relation to nutrition recommendations. However, despite many controversies surrounding milk, the respondents also claimed that it played an important role in their daily diet. The most frequently consumed type of milk in the surveyed group is ultra heat treated (UHT) milk with average fat content.


Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites.
Malaria is a prevalent and deadly disease. The fast emergence of drug-resistant malaria parasites makes the situation even worse. Thus, developing new chemical entities, preferably with novel mechanisms of action, is urgent and important. Inspired by the complex and scarce isonitrile-containing terpene natural products, we evaluated a collection of easily prepared synthetic mono- and bis-isonitrile compounds, most of which feature a simple, but rigid stilbene backbone. From this collection, potent antimalarial lead compounds with EC50 value ranging from 27 to 88 nM against the Dd2 strain using a blood stage proliferation assay were identified. Preliminary SAR information showed that the isonitrile group is essential for the observed activity against the Dd2 strain and the bis-isonitrile compounds in general perform better than the corresponding mono-isonitrile compounds.


Transcutaneous Electrical Nerve Stimulation (TENS) for the Treatment of Renal Colic in the ED: A Randomized, Double-Blind, Placebo-Controlled Trial.
To determine the analgesic efficacy of TENS treatment in patients with renal colic in the emergency department (ED). This double-blind, randomized controlled trial was conducted in a tertiary care ED. Patients with a definitive diagnosis of renal colic were assigned (1:1) as randomized to receive the real TENS with frequency 100 Hz, pulse width 200 microseconds, voltage 2 mA, or placebo with sham TENS. Pain intensity was measured using visual analog scales (VAS) at baseline, after 15 and 30th minutes. A total of 100 patients were included in the final analysis: 50 patients treated with real TENS and 50 patients treated with sham TENS. VAS scores in both groups were similar at baseline. The mean reduction in VAS score at 15 min was 33.3 ± 17.6 (95% Confidence interval (CI): 28.3 to 38.3) for the real TENS group and 14.9 ± 11.6 (95% CI 11.6 to 18.2) for the sham TENS group (mean difference: 18.4 (95% CI: 12.5 to 24.4, P < 0.0001). The mean reduction in VAS score at 30 min was 63.7 ± 21.1 (95% CI: 57.7 to 69.7) for the real TENS group and 14.9 ± 16.2 (95% CI: 19.5 to 10.3) for the sham TENS group (mean difference: 48.8, 95% CI: 41.4 to 56.3, P < 0.0001). Four patients (8%) in the real TENS group and 24 patients (48%) in the sham TENS group required the rescue medication after 30th minutes. TENS is effective for acute pain treatment in renal colic patients in the ED. TENS therapy could be a treatment option for renal colic.


Tripeptides acting on opioid receptors in rat colon.
The tripeptides SD-34 and SD-25 induced atropine-, guanethidine-, antihistaminics-resistant but naloxone-sensitive contractions of isolated rat distal colon. They appeared to act on an opioid receptor, probably of the mu subtype, distinct from those for methionine enkephalin and morphine, because the pA2 values of naloxone for the peptides were similar to those for mu-agonists but different from those for methionine enkephalin and morphine, and because the peptides caused contractions of colon that had been desensitized to morphine. Mr 2266, a supposed kappa-antagonist, inhibited the actions of the peptides, ethylketocyclazocine and dynorphin at concentrations much lower than those inhibiting the actions of methionine enkephalin and morphine. Thus these peptides seem to act on the mu- and/or kappa-receptors. The actions of the tripeptides were inhibited by methysergide and methylergometrine, but not by the 5-HT2 antagonist ketanserin, and were not affected by 5-HT or substance P autodesensitization . Thus their actions do not seem to involve 5-HT, histamine, ACh or substance P. It seems likely that the tripeptides, through opioid receptors, directly activate the muscle, or remove some inhibitory modulation of myogenic activity, thus causing contractions.


Collagen-only biomatrix as dural substitute: What happened after a 5-year observational follow-up study.
To assess long-term efficacy of the collagen-only biomatrix as a dural substitute in a large case series. We reviewed a prospectively acquired database of patients who underwent neurosurgical surgeries in whom the dural substitute was used and who were the subject of two previous studied with shorter follow-ups. The present study was conducted on 111 subjects of the original 209 patients. No late complications, nor local or systemic toxicity were observed during the observational period. As a matter of facts, 5 patients (4.5%) underwent reoperation for different reasons and 2 out of 5 experienced subcutaneous fluid collections; another case (0.9%), already reported in our previous studies, developed a CSF leak after an endoscopic endonasal operation for an intra-suprasellar arachnoid cyst. Our data further confirm that the collagen-only biomatrix derived from horse equine tendon is a safe and effective dural substitute for routine neurosurgical procedures.


Sunburn, Thermal, and Chemical Injuries to the Skin.
Sunburn, thermal, and chemical injuries to the skin are common in the United States and worldwide. Initial management is determined by type and extent of injury with special care to early management of airway, breathing, and circulation. Fluid management has typically been guided by the Parkland formula, whereas some experts now question this. Each type of skin injury has its own pathophysiology and resultant complications. All primary care physicians should have at least a basic knowledge of management of acute and chronic skin injuries.


Sonochemical degradation of triclosan in water and wastewater.
The sonochemical degradation of 5 microg l(-1) triclosan, a priority micro-pollutant, in various environmental samples (seawater, urban runoff and influent domestic wastewater) as well as in model solutions (pure and saline water) was investigated. Experiments were conducted with a horn-type sonicator operating at 80 kHz frequency and a nominal applied power of 135 W, while solid-phase microextraction coupled with gas chromatography-electron capture detector (SPME/GC-ECD) was employed to monitor triclosan degradation. The latter followed pseudo-first order kinetics with the rate constant being (min(-1)): 0.2284 for seawater>0.1051 for 3.5% NaCl in deionised water>0.0597 for centrifuged urban runoff approximately 0.0523 for untreated urban runoff >0.0272 for deionised water >0.0063 for wastewater influent. SPME/GC-ECD and SPME coupled with gas chromatography-mass spectrometry (SPME/GC-MS) were also used to check for the formation of chlorinated and other toxic by-products; at the conditions in question, the presence of such compounds was not confirmed.


An enzyme-linked immunosorbent assay for the detection of platelet antibodies using detergent-solubilized platelets immobilized on nitrocellulose discs.
A method is detailed for the solubilization of human platelets using a dialyzable detergent, decanoyl-N-methylglucamide (Mega-10). At a detergent/protein ratio of 1:12, the efficiency of solubilization was 27%. This platelet lysate (PLy) was then bound to nitrocellulose (NC) discs to assay retention of the native immunological functions of the platelet membrane antigens. Using alkaline phosphatase-coupled anti-IgG, the major platelet membrane glycoproteins GPIb, GPIIb, and GPIIb/IIIa were detectable with as little as 20 ng of monoclonal antibody. Antisera to the class I histocompatibility antigens HLA-A1, B7, B8, the PlA1 allodeterminant, and serum from multiply transfused, alloimmunized patients were reactive even after 100 days storage of the discs at 4 degrees C, and with as little as 1.0 micrograms of NC-bound PLy. The binding of the same antisera to intact, immobilized platelets as well as specific complement-mediated lymphocytotoxicity was also inhibited by PLy. PLy from HLA-A3- or B44-positive donors, however, did not inhibit cytotoxicity of lymphocytes expressing either antigen using several different antisera. Our results indicate that Mega-10 is an excellent solubilizing agent for the immunological study of platelet membranes. The fact that clinically relevant platelet membrane antigens are preserved, immunologically reactive, and stable over long periods of storage, makes this assay amenable to a routine crossmatching procedure for platelet transfusions.


Circulating tumor cells in breast cancer.
Detection of disseminated tumor cells (DTCs) in bone marrow and of circulating tumor cells (CTCs) in the blood has become a major focus of translational cancer research. DTC presence is a common phenomenon seen in 30-40% of primary breast cancer patients and is strongly associated with poor clinical outcome. Since bone marrow biopsy is an invasive procedure, evaluation of CTCs might become a desired alternative. Recent clinical trials have shown CTC detection to be a promising prognostic tool in both primary and metastatic setting. Evaluation of CTCs might be useful for therapy monitoring and their characterization might help to identify novel targets for biological therapies aimed at disrupting earliest steps of metastatic cascade.


Pediatric developmental therapies: interesting new drugs now in early-stage clinical trials.
The current high cure rates for children diagnosed with cancer can be attributed in part to emphasis on large cooperative group clinical trials. The significant improvement in pediatric cancer survival over the past few decades is the result of optimized chemotherapy drug dosing, timing, and intensity; however, further alterations in traditional chemotherapy agents are unlikely to produce substantially better outcomes. Furthermore, there remains a subset of patients who have a very poor prognosis due to tumor type or stage at presentation, or who have a dismal prognosis with relapse or recurrence. As such, innovative approaches to therapy and new drugs are clearly needed for introduction into the current pediatric oncology arsenal. A variety of biologically targeted therapies that have shown promise in preclinical studies and early-phase adult clinical trials are now being explored in pediatric clinical trials. These novel agents hold the promise for continuing to drive forward improvements in patient survival, with potentially less toxicity than exists with traditional chemotherapy drugs.