Diversity in Mission Statements and Among Students at US Medical Schools Accredited Since 2000.
Diversity in the physician workforce improves patient care and decreases health disparities. Recent calls for social justice have highlighted the importance of medical school commitment to diversity and social justice, and newly established medical schools are uniquely positioned to actively fulfill the social mission of medicine. To identify diversity language in the mission statements of all medical schools accredited since 2000 and to determine whether the presence of diversity language was associated with increased diversity in the student body. Cross-sectional study of public websites conducted between January 6, 2023, and March 31, 2023. Qualitative content analysis of mission statements was conducted using a deductive approach. Eligible schools were identified from the 2021-2022 Medical School Admission Requirements and American Medical Colleges and American Association of Colleges of Osteopathic Medicine websites. Each school's publicly available website was also reviewed for its mission and student body demographics. All United States allopathic and osteopathic medical schools that have been accredited and have enrolled students since 2000. Content analysis of medical school mission statements. Prevalence of diversity language in medical school mission statements and its association with student body racial diversity. Data were analyzed in 5-year groupings: 2001 to 2005, 2006 to 2010, 2011 to 2015, and 2016 to 2020). Among the 60 new medical schools (33 [55%] allopathic and 27 [45%] osteopathic; 6927 total students), 33 (55%) incorporated diversity language into their mission statements. In 2022, American Indian or Alaska Native individuals accounted for 0.26% of students (n = 18), Black or African American students constituted 5% (n = 368), and Hispanic or Latinx individuals made up 12% (n = 840). The percentage of schools with diversity language in their mission statements did not change significantly in schools accredited across time frames (60% in 2001: mean [SE], 0.60 [0.24] vs 50% in 2020: mean [SE], 0.50 [0.11]). The percentage of White students decreased significantly over the time period (26% vs 15% students in 2001-2005 and 2016-2020, respectively; P < .001). No significant differences were observed in student body racial or ethnic composition between schools with mission statements that included diversity language and those without. In this cross-sectional study of US medical schools accredited since 2000, diversity language was present in approximately half of the schools' mission statements and was not associated with student body diversity. Future studies are needed to identify the barriers to increasing diversity in all medical schools.


Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.
Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10-5) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.


Urine-derived Stem Cells, A New Source of Seed Cells for Tissue Engineering.
Tissue engineering, as a frontier of medicine, is aimed at regeneration of tissue and organ which can be used for the therapy of many diseases, such as trauma, cancer, and deformity. Some pluripotent stem cells are considered to be suitable for seed cells for tissue engineering, for example, bone marrow mesenchymal stem cells, adipose-derived stem cells and epidermal stem cells. Urine-derived stem cells (USCs) have been reported, and regarded as a candidate for seed cells in tissue engineering because of low-cost collection and isolation, efficient proliferation, and multidifferentiation potential, which have been documented in recent years. In this paper, we will introduce the biological characteristics of USCs and their potential applications in tissue engineering.


Community violence in context: risk and resilience in children and families.
Although some community violence research has examined the context of community violence, including the social, economic, and structural organization of neighborhoods, more needs to be learned about family, school, and community-level factors that may promote and lessen the incidence and prevalence of community violence. In addition, further research is needed on various social, environmental, and contextual factors hypothesized to protect youth from exposure. This article (a) reviews and examines the relation between neighborhood context and risk of violence exposure, (b) reviews current literature on predictors of community violence and mental health and behavioral consequences for children and families adversely affected by community violence, (c) examines sources of resilience and community strengths that extend beyond the individual, (d) discusses the contributions and limitations of current conceptualizations of risk and resilience, and (e) highlights directions for future research. Information from this review can inform community and government efforts to lessen community violence through prevention and treatment.


Synthesis and biological activity of 7 beta-(2-amino-2-carboxy)-ethylthioacetamido-7 alpha-methoxycephalosporin derivatives.
C-7 and C-3 substituents of a new antibiotic SF-1623 were chemically modified to improve the bioactivity, and substituent effect at C-7 and C-3 was examined on the basis of MIC and ED50 values against selected bacteria. Among a large number of derivatives, MT-141 possessing 2-D-2-amino-2-carboxyethylthioacetamido residue at C-7 and N-methyltetrazolyl-thiomethyl residue at C-3 showed a high order of antibacterial activity in vitro and especially in vivo.


Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine.
Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (> 20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.


Neuroinflammation and neuroimmune dysregulation after acute hypoxic-ischemic injury of developing brain.
Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia - the so-called "brain macrophages," infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds.


Human dental age estimation using third molar developmental stages: Accuracy of age predictions not using country specific information.
Unquestionable forensic age investigations are based on statistical models constructed on a sample containing subjects of identical origin as the examined individual. In cases where corresponding models are unavailable, the established report has to describe the possible effects of this unrelated information on the predicted age outcome. The aim of this study is to collect country specific databases of third molar development and to verify how the related dental age estimations are influenced if we were to use dental developmental information only from Belgium or from all collected countries together. Data containing third molar developmental stages scored following Gleiser and Hunt (modified by Köhler) were collected from 9 country specific populations (Belgium, China, Japan, Korea, Poland, Thailand, Turkey, Saudi-Arabia and South-India). Age predictions were obtained from a training dataset and validated on a test dataset. Bayes rule using the repeated third molar scores is applied to get age predictions and prediction intervals. Three age predictions were compared for males and females separately. For the first prediction, the training dataset contains only Belgian subjects. For the second prediction, the training dataset for each country consists only of subjects of the country itself. For the final prediction, subjects from all countries are pooled into one common training dataset. Besides the (absolute) difference between the chronological age and the predicted age, specific interest lies in the juvenile-adult distinction. In the age range from 16 to 22 years 6982 subjects (3189 male and 3793 female) were analyzed. Using information on third molar development from Belgium compared to information from the country specific databases hardly increased the mean absolute differences (MAD) and mean squared errors (MSE): the MAD and MSE increased on average with 0.5 and 2.5 months with maximal increases of, respectively 1.6 and 7.3 months. Using information from all countries pooled compared to country specific information provided even on average negligible increases (0.05 and 0.2 months for MAD and MSE, respectively). For the juvenile-adult discrimination, using information from all countries instead of country specific information yielded comparable performances. Using Belgium instead of country specific information increased the percentage of correctly identified juveniles, but decreased the percentage of correctly identified adults. The adult-juvenile discrimination based on information used from Belgium provides judicially the best applied reference.


Enterovesical fistula and acute pyelonephritis in renal transplantation. Role of ultrasound.
The enterovesical fistula is a communication between the urinary tract and the colon and is a rare complication of various inflammatory and cancer diseases. The most frequent cause is represented by diverticulitis of the sigmoid colon and less frequently from Crohn's disease, tumors of the colon and bladder, trauma, radiation therapy and appendicitis. In this report we describe the occurrence of an enterovesical fistula in a patient with renal allograft from a cadaveric donor, which onsetted with signs of acute pyelonephritis and pneumaturia due to diverticulitis of the sigmoid colon, clinically silent. The ultrasound in the diagnosis of enterovesical fistula, yet with a minor role compared to computed tomography (CT), is fundamental being always the first level examination.


[Functional morphology of the vascular portion of the pancreas transport system].
The vascular part of the pancreas transport system is represented by capillary bed, pericapillary space and intercellular clefts. On the surface of the acinar cells and of the fibroblasts there are cytoplasmic plates facing the pericapillary space and the intercellular clefts. The vascular part of the pancreas transport system provides delivery of the products to the acinar cells, transport of the hormones, destructed cell structures and partly of digestive enzymes to the capillaries of the pancreas.


Comparison of contrast enhanced three dimensional echocardiography with MIBI gated SPECT for the evaluation of left ventricular function.
In clinical practice and in clinical trials, echocardiography and scintigraphy are used the most for the evaluation of global left ejection fraction (LVEF) and left ventricular (LV) volumes. Actually, poor quality imaging and geometrical assumptions are the main limitations of LVEF measured by echocardiography. Contrast agents and 3D echocardiography are new methods that may alleviate these potential limitations. Therefore we sought to examine the accuracy of contrast 3D echocardiography for the evaluation of LV volumes and LVEF relative to MIBI gated SPECT as an independent reference. In 43 patients addressed for chest pain, contrast 3D echocardiography (RT3DE) and MIBI gated SPECT were prospectively performed on the same day. The accuracy and the variability of LV volumes and LVEF measurements were evaluated. Due to good endocardial delineation, LV volumes and LVEF measurements by contrast RT3DE were feasible in 99% of the patients. The mean LV end-diastolic volume (LVEDV) of the group by scintigraphy was 143 +/- 65 mL and was underestimated by triplane contrast RT3DE (128 +/- 60 mL; p < 0.001) and less by full-volume contrast RT3DE (132 +/- 62 mL; p < 0.001). Limits of agreement with scintigraphy were similar for triplane andfull-volume, modalities with the best results for full-volume. Results were similar for calculation of LV end-systolic volume (LVESV). The mean LVEF was 44 +/- 16% with scintigraphy and was not significantly different with both triplane contrast RT3DE (45 +/- 15%) and full-volume contrast RT3DE (45 +/- 15%). There was an excellent correlation between two different observers for LVEDV, LVESV and LVEF measurements and inter observer agreement was also good for both contrast RT3DE techniques. Contrast RT3DE allows an accurate assessment of LVEF compared to the LVEF measured by SPECT, and shows low variability between observers. Although RT3DE triplane provides accurate evaluation of left ventricular function, RT3DE full-volume is superior to triplane modality in patients with suspected coronary artery disease.


Association of Metabolic Obesity Phenotypes and Total Testosterone in Chinese Male Population.
Obesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population. We performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40-75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI<25.0) and overweight/obesity (BMI≥25.0) with or without metabolic syndrome. We collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414-3.911) and 3.294 (2.631-4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups. Obesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.


Medulloblastoma treatment in a child on dialysis.
Managing patients who suffer from both cancer and end-stage renal disease is challenging because there is a paucity of data, especially for children. There are no published reports of adjuvant chemotherapy for medulloblastoma being used in children on dialysis. In this article we describe the case of an Italian 5-year-old boy on hemodialysis for chronic renal failure who presented with a desmoplastic medulloblastoma with extensive nodularity and nuclear β-catenin expression. The patient was treated with craniospinal irradiation after complete surgical resection, followed by six cycles of cyclophosphamide and vincristine. Vincristine was administered at the usual dosage for children with normal kidney function, cyclophosphamide was delivered after dialysis and over the course of the following day, starting with 50% of the commonly used dosage. This is the first case report of chemotherapy given during hemodialysis in a child with medulloblastoma. This treatment proved easy to administer despite the child's kidney disease and it maintained disease remission with no additional toxicity.


Human Spermatozoa as a Model for Detecting Missing Proteins in the Context of the Chromosome-Centric Human Proteome Project.
The Chromosome-Centric Human Proteome Project (C-HPP) aims at cataloguing the proteins as gene products encoded by the human genome in a chromosome-centric manner. The existence of products of about 82% of the genes has been confirmed at the protein level. However, the number of so-called "missing proteins" remains significant. It was recently suggested that the expression of proteins that have been systematically missed might be restricted to particular organs or cell types, for example, the testis. Testicular function, and spermatogenesis in particular, is conditioned by the successive activation or repression of thousands of genes and proteins including numerous germ cell- and testis-specific products. Both the testis and postmeiotic germ cells are thus promising sites at which to search for missing proteins, and ejaculated spermatozoa are a potential source of proteins whose expression is restricted to the germ cell lineage. A trans-chromosome-based data analysis was performed to catalog missing proteins in total protein extracts from isolated human spermatozoa. We have identified and manually validated peptide matches to 89 missing proteins in human spermatozoa. In addition, we carefully validated three proteins that were scored as uncertain in the latest neXtProt release (09.19.2014). A focus was then given to the 12 missing proteins encoded on chromosomes 2 and 14, some of which may putatively play roles in ciliation and flagellum mechanistics. The expression pattern of C2orf57 and TEX37 was confirmed in the adult testis by immunohistochemistry. On the basis of transcript expression during human spermatogenesis, we further consider the potential for discovering additional missing proteins in the testicular postmeiotic germ cell lineage and in ejaculated spermatozoa. This project was conducted as part of the C-HPP initiatives on chromosomes 14 (France) and 2 (Switzerland). The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD002367.


Effect of Laurus nobilis L. Essential Oil and its Main Components on α-glucosidase and Reactive Oxygen Species Scavenging Activity.
The present study was designed to determine the effects of the essential oil of Laurus nobilis L. (Lauraceae) and its three main components on α-glucosidase and reactive oxygen species scavenging activity. The chemical composition of the essential oil from Laurus nobilis L. leaves was analyzed by GC/GC-MS and resulted in the identification of 29 compounds, representing 99.18% of the total oil. 1,8-cineole (68.82%), 1-(S)-α-pinene (6.94%), and R-(+)- limonene (3.04%) were determined to be the main components. The antioxidant features of the essential oil and its three main components were evaluated using inhibition of 2,2-diphenyl-1- picrylhydrazyl, hydroxyl, and superoxide radicals, inhibition of hydrogen peroxide and lipid peroxidation assays. The results show that the DPPH, hydroxyl, and superoxide radical as well as hydrogen peroxide scavenging activities of the essential oil are greater than the positive controls and the three main components of the oil when tested independently. The inhibition of lipid peroxidation by the oil occurred less frequently than with 1,8-cineole and R-(+)- limonene alone, but the effects were more pronounced than those seen with 1-(S)-α-pinene and the positive controls. An α-glucosidase inhibition assay was applied to evaluate the in-vitro antidiabetic activity of the essential oil. IC50-values were obtained for laurel essential oil, 1, 8-cineole, 1-(S)-α-pinene, and R-(+)-limonene: 1.748 μL/mL, 1.118 μL/mL, 1.420 μL/mL and 1.300 μL/mL, respectively. We also found that laurel essential oil and 1, 8-cineole inhibited the α-glucosidase competitively while 1-(S)-α-pinene and R-(+)-limonene were uncompetitive inhibitors.


[A family's experience of home accidents--report of an experience].
This study aims at knowing the behaviour of the family facing the home accidents among children, identifying the risk factors in the home environment, in the family's perception and analysing the socioeconomic-cultural context contributing to the occurrence of children's home accident. The work was made in a family that had experienced a case of poisoning of a 4 year-old child. Participant observation and the semi-structured interview were used as methodology. The results evidenced that the family constantly lives among children's home accidents and the socioeconomic-cultural context has a strong influence in the amount and quality of these cases.


Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction.
To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined;with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.


Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer.
In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4's regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to better understand the epigenetic regulation of CXCR4 in CRC. CXCR4 expression levels were measured using qPCR and immunoblotting in normal colon tissues, primary colon cancer tissues and CRC cell lines. Publicly available RNA-seq and methylation data from The Cancer Genome Atlas (TCGA) were extracted from tumors from CRC patients. The DNA methylation status spanning CXCR4 gene was evaluated using combined bisulfite restriction analysis (COBRA). The methylation status in the CXCR4 gene body was analyzed using previously performed nano-hmC-seal data from colon cancers and adjacent normal colonic mucosa. CXCR4 expression levels were significantly increased in tumor stromal cells and in tumor colonocytes, compared to matched cell types from adjacent normal-appearing mucosa. CXCR4 promoter methylation was detected in a minority of colorectal tumors in the TCGA. The CpG island of the CXCR4 promoter showed increased methylation in three of four CRC cell lines. CXCR4 protein expression differences were also notable between microsatellite stable (MSS) and microsatellite instable (MSI) tumor cell lines. While differential methylation was not detected in CXCR4, enrichment of 5-hydroxymethylcytosine (5hmC) in CXCR4 gene bodies in CRC was observed compared to adjacent mucosa.


Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.
Vav, a guanine nucleotide exchange factor for members of the Rho family of small GTPases, is activated through engagement of B and T lymphocyte antigen receptors. It is important for establishing the signaling threshold of the TCR, as mice lacking Vav display defective thymocyte selection. Here, conventional B cells are shown to develop normally in Vav-deficient mice but these mice have few B-1 B cells. The threshold for inducing B cell proliferation through BCR engagement in vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice have normal antibody responses to haptenated Ficoll. In contrast, Vav-/- mice show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Interestingly, this defect is reversed in chimeras where normal T cells are present. Antigen-specific proliferation of T cells in the T zone was found to be similar in wild-type and Vav-/- mice but the induction of IL-4 mRNA and switch transcripts was specifically impaired. These results suggest that defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.


Perovskite photovoltaics: a high-efficiency newcomer to the solar cell family.
Organometal trihalide perovskite-based light absorbers have attracted great attention due to their excellent photovoltaic properties. The swift developments in the device fabrication techniques have led to the power conversion efficiencies exceeding 17%. In this minireview, we will present the typical characteristics of the materials and device structures, followed by analysing updated understandings on the operational principles of the devices. We will also point out the outstanding issues regarding the materials and devices. Finally, as a high-efficiency newcomer to the solar cell family, the potential impact on the relevant photovoltaics will be discussed.


Use of the femoral vein as insertion site for tunneled hemodialysis catheters.
To determine the outcome of tunneled hemodialysis catheters inserted through the common femoral vein. From April 2000 to June 2003, 33 consecutive patients had 86 tunneled hemodialysis catheters inserted through the femoral vein. There were 14 male and 19 female patients with a mean age of 56 years. Seventeen patients had bilateral central venous and/or superior vena cava (SVC) occlusions, 12 patients had unilateral central venous occlusions and were to receive contralateral arteriovenous fistulas or arteriovenous polytetrafluoroethylene grafts, and 4 patients received femoral catheters for other reasons. The technical success, complications, and clinical outcomes of these procedures were retrospectively evaluated. All procedures were technically successful. Fifty-seven catheters were inserted into the right femoral vein and 29 into the left femoral vein. This included 25 catheter exchanges in 13 patients. Two patients developed thigh hematomas. Follow-up data were available for 68 catheters; mean follow-up period was 51 days with a total of 3,484 catheter days. The catheter-related infection rate was 6.3 per 1,000 catheter days; 22 catheters were removed for infection. Eighteen catheters were removed because of poor blood flows (<200 mL/min). Thirteen catheters were removed because they had become retracted. Primary catheter patency was 44% at 1 month. The femoral vein provides an alternative access site for insertion of tunneled hemodialysis catheters when conventional sites are not available. However, tunneled femoral hemodialysis catheters have low primary patency rates and significant complications. Catheter retraction is a unique and common problem.


Nutrition Report Cards: an opportunity to improve school lunch selection.
To explore the feasibility and implementation efficiency of Nutritional Report Cards (NRCs) in helping children make healthier food choices at school. Pilot testing was conducted in a rural New York school district (K-12). Over a five-week period, 27 parents received a weekly e-mail containing a NRC listing how many meal components (fruits, vegetables, starches, milk), snacks, and a-la-carte foods their child selected. We analyzed choices of students in the NRC group vs. the control group, both prior to and during the intervention period. Point-of-sale system data for a-la-carte items was analyzed using Generalized Least Squares regressions with clustered standard errors. NRCs encouraged more home conversations about nutrition and more awareness of food selections. Despite the small sample, the NRC was associated with reduced selection of some items, such as the percentage of those selecting cookies which decreased from 14.3 to 6.5 percent. Additionally, despite requiring new keys on the check-out registers to generate the NRC, checkout times increased by only 0.16 seconds per transaction, and compiling and sending the NRCs required a total weekly investment of 30 minutes of staff time. This test of concept suggests that NRCs are a feasible and inexpensive tool to guide children towards healthier choices.


Mechanism of hypochlorous acid-mediated heme destruction and free iron release.
Here, we show that hypochlorous acid (HOCl), a potent neutrophil-generated oxidant, can mediate destruction of free heme (Ht) and the heme precursor, protoporphyrin IX (PPIX). Ht displays a broad Soret absorbance peak centered at 365 and 394 nm, indicative of the presence of monomer and μ-oxo-dimer. Oxidation of Ht by HOCl was accompanied by a marked decrease in the Soret absorption peak and release of free iron. Kinetic measurements showed that the Ht-HOCl reaction was triphasic. The first two phases were HOCl concentration dependent and attributable to HOCl binding to the monomeric and dimeric forms. The third phase was HOCl concentration independent and attributed to Ht destruction with the release of free iron. HPLC and LC-ESI-MS analyses of the Ht-HOCl reaction revealed the formation of a number of degradation products, resulting from the cleavage or modification of one or more carbon-methene bridges of the porphyrin ring. Similar studies with PPIX showed that HOCl also mediated tetrapyrrole ring destruction. Collectively, this work demonstrates the ability of HOCl to modulate destruction of heme, through a process that occurs independent of the iron molecule that resides in the porphyrin center. This phenomenon may play a role in HOCl-mediated oxidative injury in pathological conditions.


Autoreactive CD1b-restricted T cells: a new innate-like T-cell population that contributes to immunity against infection.
Group 1 CD1 (CD1a, -b, and -c) presents self and foreign lipid antigens to multiple T-cell subsets in humans. However, in the absence of a suitable animal model, the specific functions and developmental requirements of these T cells remain unknown. To study group 1 CD1-restricted T cells in vivo, we generated double transgenic mice (HJ1Tg/hCD1Tg) that express group 1 CD1 molecules in a similar pattern to that observed in humans (hCD1Tg) as well as a TCR derived from a CD1b-autoreactive T-cell line (HJ1Tg). Using this model, we found that similar to CD1d-restricted NKT cells, HJ1 T cells exhibit an activated phenotype (CD44(hi)CD69(+)CD122(+)) and a subset of HJ1 T cells expresses NK1.1 and is selected by CD1b-expressing hematopoietic cells. HJ1 T cells secrete proinflammatory cytokines in response to stimulation with CD1b-expressing dendritic cells derived from humans as well as hCD1Tg mice, suggesting that they recognize species conserved self-lipid antigen(s). Importantly, this basal autoreactivity is enhanced by TLR-mediated signaling and HJ1 T cells can be activated and confer protection against Listeria infection. Taken together, our data indicate that CD1b-autoreactive T cells, unlike mycobacterial lipid antigen-specific T cells, are innate-like T cells that may contribute to early anti-microbial host defense.


Trajectories of Sleep Quality and Associations with Mood during the Perinatal Period.
The aim of this study was to investigate trajectories of sleep quality and associations with mood in the perinatal period. Although it is commonly accepted that subjective sleep quality declines during pregnancy and the transition to parenthood, some women may follow qualitatively distinct trajectories. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based semiparametric mixture model was used to estimate patterns of sleep quality throughout the perinatal period. Four trajectory groups were identified, including patterns defined by high sleep quality throughout (21.5%), mild decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%) and a group with poor sleep quality throughout (6.7%). Women who had the worst sleep quality at Time 1 and those who experienced significant increases in sleep problems throughout pregnancy were also the groups who reported the highest levels of anxiety and depressive symptoms in early pregnancy and the lowest levels of social support. After controlling for covariates, the groups with worst subjective sleep quality during pregnancy were also the most likely to experience high symptoms of depression in the postpartum period. Most of the women in our sample reported mild sleep disturbances through the perinatal period. A subgroup of women reported a significant decline in sleep quality from early to late pregnancy and another reported poor subjective sleep quality throughout pregnancy; these groups had the greatest risk of experiencing high symptoms of depression in the postpartum period.


Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses.
Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness.


Zinc supplementation improves glycemic control for diabetes prevention and management: a systematic review and meta-analysis of randomized controlled trials.
Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes. PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model. Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): -14.15 mg/dL; 95% CI: -17.36, -10.93 mg/dL], 2-h postprandial glucose (WMD: -36.85 mg/dL; 95% CI: -62.05, -11.65 mg/dL), fasting insulin (WMD: -1.82 mU/L; 95% CI: -3.10, -0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: -0.73; 95% CI: -1.22, -0.24), glycated hemoglobin (WMD: -0.55%; 95% CI: -0.84, -0.27%), and high-sensitivity C-reactive protein (WMD: -1.31 mg/L; 95% CI: -2.05, -0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement. Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes. This trial was registered at PROSPERO as CRD42018111838.


The association of gynecological symptoms with psychological distress in women of reproductive age: a survey from gynecology clinics in Beirut, Lebanon.
To date there has been no previous research into a possible association between psychological distress and gynecologic symptoms in the Arab world. We hypothesized that psychological distress would be associated with specific gynecologic complaints as well as with psychosocial factors. We conducted a cross-sectional study of women attending gynecology clinics in Beirut, Lebanon. The study sample consisted of 355 women aged 18 to 49 years who were seeking healthcare from gynecologists affiliated with two general teaching hospitals in Beirut. Psychological distress was assessed using the General Health Questionnaire (GHQ). Gynecologic complaints were assessed by asking women about presenting gynecologic symptoms. Women who visited the gynecologists for specific complaints, for post-surgical follow-up, or for insertion of coils or other services were more likely to be distressed than women who were attending for a general checkup (chi 2 = 9.466, p = 0.024). About 50% of women who reported abdominal pain or breast pain also reported significant psychological distress. Only bleeding and infertility were not significantly associated with psychological distress. It is concluded that a high proportion of women who attend gynecology clinics with specific complaints report psychological distress. Our findings highlight the importance of considering the psychological component of gynecological morbidity.


Penile Circular Fasciocutaneous (McAninch) Flap as an Option for Complex Anterior Urethral Stricture in Case of Non-Viable Buccal Mucosal Graft.
The penile circular fasciocutaneous flap (FCF) is employed in the successful single stage reconstruction of long segment complex anterior urethral strictures especially when buccal mucosa is unavailable due to various reasons. A 65-year-old gentleman, chronic smoker and tobacco chewer, hypertensive on treatment, presented with obstructive lower urinary tract symptoms for 8 months. He had no prior urethral catheterization. On examination, he had circumcised penis, with stenosis of the external urethral meatus. Glans had no changes suggesting balanitis xerotica obliterans. Suprapubic cystostomy was done as he developed acute urinary retention during evaluation. Retrograde urethrogram (RGU) showed pan-anterior urethral stricture. He was planned for substitution urethroplasty. On oral cavity examination, he had moderate trismus with oral submucous fibrosis. As buccal mucosal graft was unavailable, he was planned for FCF. A ventral onlay tubularization FCF urethroplasty from meatus to bulbar urethra based on dartos dorsal pedicle was done. His postoperative recovery was uneventful. Pericatheter RGU did not show extravastion and he voided well with Qmax 14 ml/second. He is doing well at follow-up.


Repigmentation in vitiligo universalis after starting dialysis-could they be related?
Vitiligo is an acquired disorder of pigmentation characterized by the development of white macules and patches on the skin. Although multiple theories have been proposed to understand the underlying pathophysiology behind the pigment loss, the exact etiology remains unknown. Vitiligo universalis is an extremely rare variant that causes nearly complete depigmentation of the entire body surface. Treatment is challenging, especially when pigment loss is generalized and diffuse. We present a unique case of a patient with vitiligo universalis that had remained untreated and stable for >20 years until she developed repigmentation shortly after initiation of dialysis.


Promising new pharmacological targets for depression: The search for efficacy.
Pharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD, as well as the preclinical and clinical evidence for an antidepressant effect of molecules that target non-serotonergic systems. We offer some insights into the challenges facing the development of new antidepressant drugs, and the prospect of finding more effectiveness for each target discussed.


[One-stop examination of thoracic and abdominal injuries in earthquake victims using multi-slice CT].
To assess the clinical value of multi-slice CT in one-stop examination of thoracic and abdominal injuries in earthquake victims. DR and multi-slice CT examination were performed in 162 earthquake victims with thoracic and abdominal injuries. Optimal processes and preferred modalities were identified through comparisons of examination time, radiation dose and diagnostic value between the two methods. The multi-slice CT took (5 +/- 2) min, shorter than that of DR (10 +/- 3) min (P < 0.001). The radiation dose of multi-slice CT (6.4 +/- 1.7) mSv was higher than that of DR (2.4 +/- 1.3) mSv (P < 0.001). Both methods were able to detect bone fracture (clavicle, rib, sternum, thoracic spine, lumbar and pelvic). However, soft-tissue organ trauma, such as liver, pancreas and spleen could not be detected by DR. Multi-slice CT had significantly higher sensitivity (98%) and specificity (97%) in detecting thoracic and abdominal injuries than DR (74%, 67%). Multi-slice CT one-stop examination is a preferred method for detecting combined injuries in emergency events, as it can save examination time and obtain reliable diagnostic information.


Gene expression profile in metastatic and non-metastatic parathyroid carcinoma.
Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs PAs and in metastatic PCs vs non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.


E-learning adoption in pre-registration training.
Despite the advances in technology and the many ways in which it can be used in education, many academics are reluctant to include technology in their teaching. Past studies have been unsuccessful in finding out the reasons for this. This article analyses a study that looked into the reasons why nurse educators in particular are reluctant to adopt technology in their teaching practice.


Genetic variation in four maturity genes affects photoperiod insensitivity and PHYA-regulated post-flowering responses of soybean.
Absence of or low sensitivity to photoperiod is necessary for short-day crops, such as rice and soybean, to adapt to high latitudes. Photoperiod insensitivity in soybeans is controlled by two genetic systems and involves three important maturity genes: E1, a repressor for two soybean orthologs of Arabidopsis FLOWERING LOCUS T (GmFT2a and GmFT5a), and E3 and E4, which are phytochrome A genes. To elucidate the diverse mechanisms underlying photoperiod insensitivity in soybean, we assessed the genotypes of four maturity genes (E1 through E4) in early-flowering photoperiod-insensitive cultivars and their association with post-flowering responses. We found two novel dysfunctional alleles in accessions originally considered to have a dominant E3 allele according to known DNA markers. The E3 locus, together with E1 and E4, contained multiple dysfunctional alleles. We identified 15 multi-locus genotypes, which we subdivided into 6 genotypic groups by classifying their alleles by function. Of these, the e1-as/e3/E4 genotypic group required an additional novel gene (different from E1, E3, and E4) to condition photoperiod insensitivity. Despite their common pre-flowering photoperiod insensitivity, accessions with different multi-locus genotypes responded differently to the post-flowering photoperiod. Cultivars carrying E3 or E4 were sensitive to photoperiod for post-flowering characteristics, such as reproductive period and stem growth after flowering. The phytochrome A-regulated expression of the determinate growth habit gene Dt1, an ortholog of Arabidopsis TERMINAL FLOWER1, was involved in the persistence of the vegetative activity at the stem apical meristem of flower-induced plants under long-day conditions. Diverse genetic mechanisms underlie photoperiod insensitivity in soybean. At least three multi-locus genotypes consisting of various allelic combinations at E1, E3, and E4 conferred pre-flowering photoperiod insensitivity to soybean cultivars but led to different responses to photoperiod during post-flowering vegetative and reproductive development. The phyA genes E3 and E4 are major controllers underlying not only pre-flowering but also post-flowering photoperiod responses. The current findings improve our understanding of genetic diversity in pre-flowering photoperiod insensitivity and mechanisms of post-flowering photoperiod responses in soybean.


Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma.
We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2-181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper's most important limitations include its retrospective nature and its relatively small number of patients. No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function.


Contraception for the insulin-dependent diabetic woman: the view from one clinic.
Experience in a large diabetic clinic has confirmed the suspicion that insulin-dependent diabetic women are at considerably increased risk of thromboembolic disease if they take combined estrogen/progestogen oral contraceptive preparations. The most obvious alternative, an intrauterine device, is associated with an unexpectedly high failure rate, probably because of an unusual metabolic interaction with the diabetic endometrium. In a small group of diabetic women the progestogen-only pill was found to be a successful form of contraception not associated with any side effects except for menstrual irregularities. For most diabetic women the choice of contraceptive should therefore be between a progestogen-only pill and a mechanical method. Female sterilization and injectable progesterone each have their place in particular circumstances. Careful counseling of each patient is essential to ensure the best choice of contraceptive and correct application of the chosen method.


Acute cerebellitis, transverse myelitis and polyradiculoneuritis related to post-COVID-19 infection.
Guillain-Barré syndrome (GBS), acute cerebellitis and transverse myelitis are rare complications of COVID-19 infection separately. The combination of these three, however, has not yet been reported. We present an atypical case (42-year-old man) that developed acute ascending flaccid paraparesis, ataxia and urinary retention two weeks after COVID-19 infection. Neurological examination revealed distal and proximal weakness (4/5) on lower extremities, decreased tendon reflexes, sixth cranial nerve palsy and dysmetria without sensory disturbance. His cranial MRI showed cerebellitis whereas the spinal MRI showed transverse myelitis at the T11/12 level. Albuminocytologic dissociation was present in the cerebrospinal fluid. The nerve conduction study was concordant with early findings of GBS. He recovered well after corticosteroid treatment without needing any immunotherapy. On day seven of hospitalization, the modified Rankin Scale score was 0. COVID-19 infection may present with a combination of neurological manifestations such as cerebellitis, transverse myelitis and GBS. This patient presented significant functional recovery after treatment with corticosteroid without immunotherapy.


Long-term stabilisation of myeloma with curcumin.
Myeloma is a haematological malignancy which typically follows a relapsing-remitting course. While treatment can control the myeloma and improve quality of life for given periods of time, remissions generally become progressively shorter with subsequent relapses, and patients ultimately enter a final refractory phase. To help control symptoms and enhance quality of life, some patients use complementary therapies as an adjunct to their conventional therapy. Here, we describe a myeloma patient who started a daily dietary supplement of curcumin when approaching her third relapse. In the absence of further antimyeloma treatment, the patient plateaued and has remained stable for the last 5 years with good quality of life.


Preliminary evaluation of a novel bladder-liner for facilitating residual limb fluid volume recovery without doffing.
For people who wear a prosthetic limb, residual-limb fluid volume loss during the day may be problematic and detrimentally affect socket fit. The purpose of this research was to test the capability of a novel liner with adjustable bladders positioned within its wall to mitigate volume loss and facilitate limb fluid volume recovery and retention. Bioimpedance analysis was used to monitor fluid volume changes in the anterior and posterior residual limb of participants with transtibial amputation. Participants underwent six cycles of sitting for 90 s, standing for 90 s, and walking for 5 min with liquid within the bladder-liners. Between the third and fourth cycles, participants sat for 10 min with liquid left within the bladders (Liquid-In) or removed (Liquid-Out). Results showed that participants recovered more fluid volume during the 10 min of sitting with Liquid-Out than Liquid-In (p = 0.09 for anterior and p = 0.04 for posterior). However, those fluid volume recoveries were not well retained in the short term (after the fourth cycle) or the long term (after the sixth cycle). Physiologic differences between sessions, reflected in the rates of fluid volume change at the outset of the session, and excessive stiffness of the bladder-liners may have affected fluid volume retentions.


Bazex syndrome. Follicular atrophoderma and basal cell epitheliomas.
A dominant inheritance leading to development of nevoid basal cell epitheliomas on the face and follicular atrophoderma on the extremities constitute the two constant manifestations of Bazex syndrome. A patient with both manifestations on the trunk who fulfilled all the criteria for a diagnosis of nevoid basal cell epitheliomas is described. Histopathology of the basal cell cancer corresponded to that of the fibroepithelial tumor, thus differing from the more common nodular and trichoepitheliomatous presentations. Difficulty in associating the atrophoderma with a hair follicle (histologically) arises because the latter ceases to exist as a functional unit.


Molluscum contagiosum. Ultrastructural evidence for its presence in skin adjacent to clinical lesions in patients infected with human immunodeficiency virus type 1. Military Medical Consortium for Applied Retroviral Research.
Molluscum contagiosum in acquired immunodeficiency disease, although not life threatening, is often a marker of late-stage disease and may lead to disfiguring cutaneous lesions. Although most current therapy results in at least temporary clearing of individual lesions, lesions frequently recur and new lesions arise. Examination of hematoxylin-eosin-stained histologic sections in two patients showed changes suggestive of viral infection in the epidermis 0.5 cm and 1 cm lateral to obvious clinical lesions. These areas were clinically free of any lesions. Both routine histopathologic examination and ultrastructural examination were performed in two patients infected with human immunodeficiency virus type 1 (HIV-1) and three non-HIV-1-infected patients. All patients showed histologic changes diagnostic of molluscum contagiosum. In addition, the sections from HIV-1-infected patients showed areas of acanthosis, hyperkeratosis, and nuclear atypia. Electron microscopy of these areas revealed rare viral organisms in these areas. Similar acanthotic, hyperkeratotic areas were not seen in the biopsy specimens from the non-HIV-1-infected patients and no viral particles were found in the epidermis around the lesions. Viral structures consistent with molluscum contagiosum are present within the clinically normal epidermis around lesions of molluscum contagiosum in some HIV-1-infected patients. This may explain the large number of lesions seen in these patients and the difficulty in controlling the spread and recurrence of molluscum contagiosum in HIV-1-infected patients.


Quantitative affinity chromatography. Determination of binding constants by elution with competitive inhibitors.
The affinity chromatographic separation procedure was tested for its utility in quantitating the affinity of proteins to both insolubilized ligand and corresponding competing soluble ligand. An expression has been derived that (1) allows the determination of binding constants for the interaction of a soluble protein species with an affinity chromatography matrix involving active site binding, (2) yields binding constants for the interaction of the protein with soluble ligands that can compete with the insoluble matrix for binding to the active site of the protein, and (3) utilizes readily obtainable parameters from conventional chromatography. This expression has been applied to the quantitation of the binding of staphylococcal nuclease to thymidine-5'-phosphate-3'-amino-phenylphosphate-Sepharose in competition with thymidine-3',5'-bisphosphate.


Role of angiotensinogen in blood pressure homeostasis.
The role of angiotensinogen in blood pressure control was assessed in normotensive rats by observing the changes resulting from inhibition by specific rat angiotensinogen antiserum. The antiserum decreased blood pressure in rats on normal sodium as well as sodium-free diets (respectively delta BP = -30 +/- 6 mm Hg and -42 +/- 8 mm Hg). In binephrectomized sodium-replete rats, administration of antiserum did not reduce blood pressure, whereas in sodium-depleted animals it slightly decreased blood pressure by 11 +/- 3 mm Hg. These results suggest that angiotensinogen participates in the regulation of blood pressure in normotensive rats, even in the sodium-replete state.


Difference in tissue temperature change between two cryoballoons.
Cryoballoon ablation, especially Arctic Front Advance Pro (AFA-Pro) (Medtronic, Minneapolis, Minnesota, USA), has been widely recognised as a standard approach to atrial fibrillation (AF). Recently, Boston Scientific has released a novel cryoballoon system (POLARx). Despite comparable acute clinical outcomes of these two cryoballoons, the recent study reported a higher complication rate, especially for phrenic nerve palsy, with POLARx. However, their impact on biological tissue remains unclear. The purpose of our study is to evaluate temperature change of biological tissue during cryoablation of each cryoballoon using a porcine experimental model. A tissue-based pulmonary vein model was constructed from porcine myocardial tissue and placed on a stage designed to simulate pulmonary vein anatomy and venous flow. Controlled cryoablations of AFA-Pro and POLARx were performed in this model to evaluate the tissue temperature. A temperature sensor was set behind the muscle and cryoballoon ablation was performed after confirming the occlusion of pulmonary vein with cryoballoon. The mean tissue nadir temperature during cryoablation with AFA-Pro was -41.5°C±4.9°C, while the mean tissue nadir temperature during cryoablation with POLARx was -58.4°C±5.9°C (p<0.001). The mean balloon nadir temperature during cryoablation with AFA-Pro was -54.6°C±2.6°C and the mean balloon nadir temperature during cryoablation with POLARx was -64.7°C±3.8°C (p<0.001). POLARx could freeze the biological tissue more strongly than AFA-Pro.


The extracellular matrix proteins laminin and fibronectin contain binding domains for human plasminogen and tissue plasminogen activator.
This study describes the binding of plasminogen and tissue-type plasminogen activator (t-PA) to the extracellular matrix proteins fibronectin and laminin. Plasminogen bound specifically and saturably to both fibronectin and laminin immobilized on microtiter wells, with Kd(app) values of 115 and 18 nM, respectively. Limited proteolysis by endoproteinase V8 coupled with ligand blotting analysis showed that both plasminogen and t-PA preferentially bind to a 55-kDa fibronectin fragment and a 38-kDa laminin fragment. Amino acid sequence analysis demonstrated that the 5-kDa fragment originates with the fibronectin amino terminus whereas the laminin fragment was derived from the carboxyl-terminal globular domain of the laminin A chain. Ligand blotting experiments using isolated plasminogen domains were also used to identify distinct regions of the plasminogen molecule involved in fibronectin and laminin binding. Solution phase fibronectin binding to immobilized plasminogen was mediated primarily via lysine binding site-dependent interactions with plasminogen kringles 1-4. Lysine binding site-dependent binding of soluble laminin to immobilized plasminogen kringles 1-5 as well as an additional lysine binding site-independent interaction between mini-plasminogen and the 38-kDa laminin A chain fragment were also observed. These studies demonstrate binding of plasminogen and tissue-type plasminogen activator to specific regions of the extracellular matrix glycoproteins laminin and fibronectin and provide further insight into the mechanism of regulation of plasminogen activation by components of the extracellular matrix.


[Stepwise dissociation of subcomponents of C1, the first component of human complement, upon activation on an affinity sorbent].
An affinity sorbent comprising macroporous glass coated with the polymer with the polymer with immobilized immunoglobulin IgG was used for the isolation from human serum of the first component of the complement and for its separation into subcomponents C1r, C1s and C1q by the one-step procedure. Serum C1 was quantitatively bound to the sorbent at 0 degrees C. The unbound part of the serum can be used as a R1 reagent for determining the hemolytic activity of C1. After activation of bound C1 by heating (30 degrees C, 40 min) the activated subcomponent C1r is eluted from the sorbent. Stepwise elution with EDTA at pH 7.4 or with EDTA + 1 M NaCl at pH 8.5 results in a selective and quantitative elution of the activated subcomponent C1s and subcomponent C1q. Stepwise elution of C1 subcomponents from the affinity sorbent after activation reflects the process of C1 breakdown following its activation on immune complexes.


The structure of H-2K(b) and K(bm8) complexed to a herpes simplex virus determinant: evidence for a conformational switch that governs T cell repertoire selection and viral resistance.
Polymorphism within the MHC not only affects peptide specificity but also has a critical influence on the T cell repertoire; for example, the CD8 T cell response toward an immunodominant HSV glycoprotein B peptide is more diverse and of higher avidity in H-2(bm8) compared with H-2(b) mice. We have examined the basis for the selection of these distinct antiviral T cell repertoires by comparing the high-resolution structures of K(b) and K(bm8), in complex with cognate peptide Ag. Although K(b) and K(bm8) differ by four residues within the Ag-binding cleft, the most striking difference in the two structures was the disparate conformation adopted by the shared residue, Arg(62). The altered dynamics of Arg(62), coupled with a small rigid-body movement in the alpha(1) helix encompassing this residue, correlated with biased Valpha usage in the B6 mice. Moreover, an analysis of all known TCR/MHC complexes reveals that Arg(62) invariably interacts with the TCR CDR1alpha loop. Accordingly, Arg(62) appears to function as a conformational switch that may govern T cell selection and protective immunity.


Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent.
Medicinal plants have always had great value for the human population due to their valuable constituents and potential bioactivities. The objective of this review is to present an updated overview of an important medicinal plant genus Nepeta L., from the family Lamiaceae, revealing its traditional utilization, biological activity, phytoconstituents, and mechanisms of action. For this purpose, a literature survey was carried out by using SciFinder, ScienceDirect, Scopus, PubMed, and Web of Science followed by a revision of the bibliographies of the related articles. We have described and analyzed the role of plants in drug discovery and the importance of Nepeta species. Information on the utilization purposes of Nepeta species in folk medicine has been emphasized, and scientific studies on the biological effects and secondary metabolites are addressed. Nepeta species are characterized by terpenoid-type compounds and phenolic constituents, which exert several activities such as an antimicrobial, repellent against major pathogen vector mosquitoes, insecticide, larvicide against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant, anticonvulsant, analgesic, anti-inflammatory agent, and antidepressant, revealing its importance in medicinal and agricultural fields. On the basis of numerous studies, the Nepeta genus demonstrates remarkable therapeutic effects against various diseases. However, clinical studies are warranted to confirm preclinical findings.


An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis.
Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing "cellular" fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.


Real-time three-dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography.
This study was designed to test the feasibility and efficacy of using real-time three-dimensional echocardiography (RT-3D) to detect ischemia during dobutamine-induced stress (DSE) and compares the results with conventional two-dimensional echocardiography (2D). Real-time three-dimensional echocardiography, a novel imaging technique, offers rapid acquisition with multiple simultaneous views of the left ventricle (LV). These features make it attractive for application during stress. Of 279 consecutive patients screened for image quality by 2D, 253 patients with adequate images underwent RT-3D and 2D within 30 s of each other at baseline and at peak DSE. Real-time three-dimensional echocardiography and 2D showed good concordance in detection of abnormal LV wall motion at baseline (84%: Kappa = 0.59) and at peak DSE (88.9%: Kappa = 0.72). Left ventricular wall motion scores were similar at baseline and peak DSE using both techniques. Interobserver agreements for detection of ischemia at peak DSE were superior for RT-3D, 92.7% compared with 84.6% for 2D (p < 0.05). Mean scanning time at peak stress by RT-3D in 50 randomly selected patients was shorter, 27.4 +/- 10.7 s compared with 62.4 +/- 20.1 s by 2D (p < 0.0001). In 90 patients with coronary angiograms, RT-3D had a sensitivity of 87.9% in the detection of coronary artery disease (CAD) compared with 79.3% by 2D. Real-time three-dimensional dobutamine stress echocardiography is feasible and sensitive in the detection of CAD. The procedure offers shorter scanning time, superior interobserver agreements and unique new views of the LV.


[Effects of ursolic acid on liver-protection and bile secretion].
To study the liver-protection and promoting bile secretion of ursolic acid. Ursolic acid was administrated to the mice with liver injury induced by CCl4 or APIT. ALT, AST levels in serum were examined. The bile flow rate and the concentration of the main components in the bile of rats administrated with ursolic acid were estimated. Ursolic acid could decrease the serum ALT, AST, SB levels in the mice treated with CCl4 or APIT, promote the secretion of bile and increase the concentration of bilirubin in the bile. Ursolic acid exhibited significant liver protection and promoting blie secretion.


Conjunctival-associated lymphoid tissue: evidence for a role in the secretory immune system.
A specialized lymphoid tissue in rabbit conjunctiva was studied by various histologic and immunologic techniques and compared with similar structures along other mucosal surfaces. The flattened conjunctival lymphoepithelium overlying the lymphoid follicles was devoid of goblet cells. This lack of goblet cells is characteristic of epithelium overlying similar lymphoid collections in gut and bronchus. The lymphoid follicles demonstrated neither intra- nor extracellular immunoglobulin, and the lymphocytes in these follicles were composed of B-cells and T-cells, when studied by various immunologic techniques. A high proportion of these lymphocytes showed surface immunoglobulin A (IgA), and a high proportion of IgA precursors were determined by pokeweed mitogen (PWM) stimulation in 4-day cultures. The morphologic and immunologic results are similar to those obtained from gut and bronchus, tissues known to disseminate lymphoid cells to other mucosal sites already committed to antigen and IgA isotype. It is speculated that conjunctival associated lymphoid tissue of rabbit is part of a generalized system of secretory immunity capable of sampling conjunctival applied antigen, and then disseminating cells committed to IgA antibody production to other mucosal sites.


Ease of retrieval effects in social judgment: the role of unrequested cognitions.
The present research explores a new mechanism for ease of retrieval effects in social judgment. It is suggested that in the most common ease of retrieval paradigm, when it is difficult for people to generate or retrieve the specific type of cognition requested (e.g., positive thoughts about an issue or memories of assertive behavior), they are more likely to spontaneously generate or retrieve unrequested cognitions (e.g., negative thoughts about the issue or memories of unassertive behavior), and the presence of these unrequested cognitions can affect social judgment. In 4 experiments, participants were asked to generate a high (difficult) or low (easy) number of cognitions in a given direction. Across experiments, when participants were asked to generate a high number of cognitions, they also had more unrequested cognitions, and these unrequested cognitions played a mediating role in the ease of retrieval effect on judgment. In the 3rd and 4th experiments, this mechanism was found to be independent of previously identified mediators.


Till Death Do Us Part: The Marriage of Autophagy and Apoptosis.
Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, it lowers cellular ROS thereby restoring cellular homeostasis. However, if cellular homeostasis cannot be reached, the cells can switch back and choose a regulated cell death response. Intriguingly, the autophagic and cell death machines both respond to the same stresses and share key regulatory proteins, suggesting that the pathways are intricately connected. Here, the intersection between autophagy and apoptosis is discussed with a particular focus on the role ROS plays.


Sleep in post-traumatic stress disorder and panic: convergence and divergence.
Disturbed sleep is a common clinical problem in anxiety disorders, particularly in patients with post-traumatic stress disorder (PTSD) and panic disorder (PD). Several studies have attempted to validate the subjective sleep complaints of these disorders using laboratory polysomnography. These attempts, typically focusing on PTSD or PD independently, have demonstrated inconsistent results. To our knowledge, no such studies have attempted to directly compare and contrast sleep disturbances in PTSD and PD together. Our review of the studies of subjective sleep disturbances, sleep architecture, and sleep-related biologic phenomena suggests that a comparative characterization of sleep disturbances in these two disorders is timely. Such an inference is based on our identification of several areas of convergence and divergence between PTSD and PD found in the published literature, as well as our own preliminary investigations. Specifically, PTSD and PD seem to converge on several sleep-related parameters, namely, sleep quality, presence of episodic parasomnias, and movement time. They also appear to diverge in other important sleep-related areas such as respiratory disturbances and the particular phenomenological nature of episodic parasomnias, namely nightmares or nocturnal panic attacks. Investigations focusing on such overlapping phenomena may provide groundwork for further elucidation of central fear systems underlying these two disorders. Additionally, such sleep studies have the potential to provide important insights into ongoing efforts to develop a cohesive conceptual framework into the patho-physiologies of these disorders.


Postnatal regulation of canine oxygen delivery: control of erythrocyte 2,3-DPG levels.
The oxygen affinity of canine blood changes markedly following birth. These changes are correlated with alterations in the intracellular concentration of 2,3-diphosphoglycerate (2,3-DPG). We have examined the control of erythrocyte glycolysis by measurements of intracellular enzymes and intermediates, and we have identified the component responsible for regulation of 2,3-DPG concentration and hence blood oxygen affinity during canine postnatal development. The concentration of 2,3-DPG could be regulated entirely by the enzymes of the Rapoport-Luebering shunt. We have not detected any alterations in the levels or intracellular activity of 2,3-DPG mutase or 2,3-DPG phosphatase during development; therefore postnatal changes of 2,3-DPG must be a result of changes in the intracellular concentrations of 1,3-diphosphoglycerate (1,3-DPG) that are controlled by other reactions in the glycolytic pathway. Neither low intracellular concentrations of glucose, the glycolytic substrate, nor an inherently low glycolytic rate can account for the low 2,3-DPG levels at birth. 1,3-DPG concentrations and hence 2,3-DPG concentrations are controlled by the activity of pyruvate kinase, which acts as a glycolytic sink reaction. The intracellular activity of pyruvate kinase decreases during the first 50-60 days of age and causes the accumulation of 2,3-DPG. There is a subsequent change in the in vivo kinetic properties of the enzyme, giving increased intracellular activity and resulting in the slow decline of 2,3-DPG concentrations toward normal adult values.


Frequency-Dependent Quadratic Response Properties and Two-Photon Absorption from Relativistic Equation-of-Motion Coupled Cluster Theory.
We present the implementation of quadratic response theory based upon the relativistic equation-of-motion coupled cluster method. We showcase our implementation, whose generality allows us to consider both time-dependent and time-independent electric and magnetic perturbations, by considering the static and frequency-dependent hyperpolarizability of hydrogen halides (HX, X = F-At), providing comprehensive insights into their electronic response characteristics. Additionally, we evaluated the Verdet constant for noble gases Xe and Rn and discussed the relative importance of relativistic and electron correlation effects for these magneto-optical properties. Finally, we calculate the two-photon absorption cross sections of transition [ns1S0 → (n + 1)s1S0] of Ga+ and In+, which are suggested as candidates for new ion clocks. As our implementation allows for the use of nonrelativistic Hamiltonians as well, we have compared our EOM-QRCC results to the QR-CC implementation in the DALTON code and show that the differences between CC and EOMCC response are in general smaller than 5% for the properties considered. Collectively, the results underscore the versatility of our implementation and its potential as a benchmark tool for other approximated models, such as density functional theory for higher-order properties.


New diagnostic and therapeutic frontiers in eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a relatively new disease that is increasingly recognized as a chronic inflammatory condition with currently evolving diagnostic and therapeutic aspects. There is data to support the rising prevalence of EOE especially in western countries. EoE is an emerging cause of dysphagia and food bolus impaction in adults as well as abdominal pain, feeding disorders, and gastroesophageal reflux-like symptoms in younger patients. EoE is ever more recognized as a separate disease process that is more complicated than eosinophilic infiltration from gastroesophageal reflux disease. Food and environmental antigens both play significant roles in stimulating T-helper (Th-2) inflammatory response. Current therapeutic options include use of proton-pump inhibitors, immunosuppressive drugs, elimination diets, and esophageal dilatation. Simple elimination of food and environmental antigen exposure can be challenging in adults due to the difficulty in accurately identifying triggering antigens and adherence to restrictive diets from a wide range of putative food allergens. Novel therapeutic options are being presented as potential treatments that target chemokines and specific immunologic mechanisms for EoE. This review will aim to summarize the latest and evolving approaches to EoE diagnosis and management. In the future, biomarkers of inflammatory response may help diagnose, treat, and stratify individual patients for better treatment outcomes with this chronic disease.


Decoration of reduced graphene oxide by gold nanoparticles: an enhanced negative photoconductivity.
Photodetection in a visible light region is important in various applications, including computation, environmental monitoring, biological detection and industrial control. Due to this, research studies to develop photoconductive devices have great significance. We report a study on the photoconductivity of reduced graphene oxide (rGO)/gold nanoparticle (AuNP) nanocomposites, emphasizing the enhancement effect induced by AuNPs. rGO/AuNP photoelectric devices were prepared by spincoating rGO onto an AuNP-array-covered silicon substrate. Photoelectric responses under visible light illumination were measured and the results showed that the negative photoelectric responsivity of rGO was improved by 3 orders of magnitude due to AuNPs. The effects of AuNPs on negative photoconductivity (NPC) properties of rGO were investigated, and it was found that AuNPs affected NPC in three aspects: (1) AuNPs form discrete electrodes separated by nanoscale gaps which generated new conduction paths, and hence the conductivity of rGO was enhanced by 3 orders of magnitude; (2) localized surface plasmon resonance (LSPR) of AuNPs effectively enhances total light absorption of rGO; (3) photocurrent between AuNPs and rGO can weaken the NPC property of rGO. The low-cost and mass-producible rGO/AuNP nanocomposites demonstrate high photoelectric responsivity, which hold much promise for NPC devices.


Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine.
The action potential of guinea pig papillary muscle exposed to the ceveratrum alkaloid germitrine (2 mugM) is followed by a long-lasting after-depolarization (maximal amplitude, 8 mV; half-time of decay, 32 seconds; total duration, approximately 75 seconds). This after-depolarization interrupts the terminal phase of repolarization. During repetitive stimulation (0.1-1.0 Hz; 80 nM germitrine) the after-depolarizations that follow consecutive action potentials are summed, causing persistent depolarization of up to 10 mV. The after-depolarization is reversibly abolished by tetrodotoxin (TTX). Test contractions evoked at various times during or after the germitrine-induced after-depolarization reveal a phase during which the ability of the muscle to develop force is transiently increased. This positive inotropic influence reaches its maximum 1 minute after the conditioning stimulus and thereafter decays with a half-time 4.8 times longer than the half-time of decay of the after depolarization. It is reversibly abolished by TTX and augmented by dihydro-ouabain (DHO). We conclude: Germitrine induces an after-depolarization by prolonging dramatically the Na permeability component which is mediated by the fast Na channels and normally restricted to the first few milliseconds of the action potential. The germitrine-induced selective and persistent increase of sarcolemmal sodium permeability (PNA) causes a positive inotropic effect, probably because intracellularly accumulating Na ions exchange for extracellular Ca ions.


Home culturing program for children with recurrent bacteriuria.
One hundred forty-one children were selected from a clinic for children with recurrent bacteriuria to participate in a home culturing program. The parent was taught to employ a semiquantitative method to test the child's urine for bacteria. The degree and persistence of bacteriuria as detected by the parent strongly correlated with results obtained in the clinic, although there was a significant incidence of false-positive results as detected by the parent. Home culturing proved to be an inexpensive, reliable technique for following up children with recurrent urinary tract infections.


Myocardial disposition and cardiac pharmacodynamics of verapamil in the dog.
The disposition of verapamil was studied in anesthetized open-chested dogs following administration of intravenous doses of 0.5 mg/kg. The plasma and myocardial verapamil concentration-time data were fit to a three-compartment model to describe the disposition kinetics. The distribution equilibrium between myocardium and plasma was achieved rapidly and the concentration of verapamil decayed in parallel in these two tissues. The partition coefficient which describes the time averaged myocardial/plasma concentration ratio was 6.21 +/- 2.38. Examination of the relationship between the plasma and myocardial concentrations and the time course of the effect of verapamil, as defined as PR interval prolongation, revealed a hysteresis effect in some dogs. Despite this hysteresis, there was a linear relationship between plasma and myocardial concentrations of verapamil and the degree of prolongation of the PR interval. The results of this study indicate that the concentration in the plasma is in equilibrium with the myocardium and changes in plasma concentration are indicative of parallel changes in myocardial levels. The effect of verapamil on the atrioventricular node is related to the concentration in the myocardium and plasma, but there is substantial interanimal variability in the sensitivity to verapamil.


Laboratory experiments in economics: the implications of posted-price institutions.
In recent years a methodology for performing laboratory experiments in economics has been developed. The object of the methodology is to integrate clearly motivated but largely subjectively determined human decisions with the organizational features of markets. The nature of the incentive system and the use of market organization as an independent variable are described. Initial results of basic research that involved assessment of the effects of the "posted-price" institution demonstrated that the effect of the institution is to raise prices and lower market efficiency. The existence of such effects and the close proximity of the laboratory posted-price institution to the rate-posting institution required by the government in several industries has led to a series of policy-related experiments. The results have also led to more basic research efforts on seemingly unrelated topics.


Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation.
Injectable and implantable porosified silicon (pSi) carriers and devices for prolonged and controlled delivery of biotherapeutics offer great promise for treatment of various chronic ailments and acute conditions. Polyethylene glycols (PEGs) are important surface modifiers currently used in clinic mostly to avoid uptake of particulates by reticulo-endothelial system (RES). In this work we show for the first time that covalent attachment of PEGs to the pSi surface can be used as a means to tune degradation kinetics of silicon structures. Seven PEGs with varying molecular weights (245, 333, 509, 686, 1214, 3400, and 5000 Da) were employed and the degradation of PEGylated pSi hemispherical microparticles in simulated physiological conditions was monitored by means of ICP-AES, SEM, and fluorimetry. Biocompatibility of the systems with human macrophages in vitro was also evaluated. The results clearly indicate that controlled PEGylation of silicon microparticles can offer a sensitive tool to finely tune their degradation kinetics and that the systems do not induce release of proinflammatory cytokines IL-6 and IL-8 in THP1 human macrophages.


Alcohol Intake and Risk of Lethal Prostate Cancer in the Health Professionals Follow-Up Study.
It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death. This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs. Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007). Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.


The frequency of heparin induced thrombocytopenia in patients undergoing elective cardiac bypass surgeries.
To determine the frequency of Heparin Induced Thrombocytopenia (HIT) in patients undergoing elective cardiac bypass surgeries and to observe the platelets evolution post surgically in these patients. A prospective study was designed and 100 unselected consecutive patients undergoing elective cardiac bypass surgery were enrolled and evaluated. The clinical and laboratory details were noted before and after surgery. Their platelet counts were observed from day 0 (prior to surgery) to day 5 post operatively. Particle gel immunoassay was used to demonstrate the presence of antibodies against heparin-platelet factor 4 complexes. There were 86 males and 14 females with median age of 59 and 53.5 years respectively. Marked platelet count variation was detected during post operative period in all patients (n=100) ranging from 23 +/- SD 186.73 to 389 +/- 84.12 X 109/L. However, 20 patients showed >50% drop on day 5 and seven of these also showed seroconversion. The clinical scoring for HIT was found to have a good negative predictive value. Thromboembolic complications were not observed in any of our patients. HIT is prevalent to a significant extent in patients after cardiac surgery in our clinical setting though it mostly remains undetected and is an under-diagnosed entity.