The synthesis of [14C] streptozotocin and its distribution and excretion in the rat.
[(14)C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity of synthetic streptozotocin was characterised by studies in vivo of its diabetogenic activity and its dose-response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-(14)C]streptozotocin and [2'-(14)C]streptozotocin the injected radioactivity was excreted (approx. 70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8% respectively) were found in the faeces. In contrast, with [3'-methyl-(14)C]streptozotocin a much smaller proportion (approx. 42%) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53% of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3'-methyl-(14)C]streptozotocin. There was no accumulation of [1-(14)C]streptozotocin in the pancreas for the 6h period after administration. However, with [3'-methyl-(14)C]streptozotocin (and also [2'-(14)C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.


Comparison of nested PCR with immunofluorescent-antibody assay for detection of Ehrlichia canis infection in dogs treated with doxycycline.
A partial 16S rRNA gene was amplified in Ehrlichia canis-infected cells by nested PCR. The assay was specific and did not amplify the closely related Ehrlichia chaffeensis, Ehrlichia muris, Neorickettsia helminthoeca, and SF agent 16S rRNA genes. The assay was as sensitive as Southern hybridization, detecting as little as 0.2 pg of E. canis DNA. By this method, all blood samples from four dogs experimentally infected with E. canis were positive as early as day 4 postinoculation, which was before or at the time of seroconversion. One hundred five blood samples from dogs from Arizona and Texas (areas of E. canis endemicity) and 30 blood samples from dogs from Ohio (area of E. canis nonendemicity) were examined by nested PCR and immunofluorescent-antibody (IFA) test. Approximately 84% of dogs from Arizona and Texas had been treated with doxycycline before submission of blood specimens. Among Arizona and Texas specimens, 46 samples were PCR positive (44%) and 80 were IFA positive (76%). Forty-three of 80 IFA-positive samples (54%) were PCR positive, and 22 of 25 IFA-negative samples (88%) were negative in the nested PCR. None of the Ohio specimens were IFA positive, but 5 specimens were PCR positive (17%). Our results indicate that the nested PCR is highly sensitive and specific for detection of E. canis and may be more useful in assessing the clearance of the organisms after antibiotic therapy than IFA, especially in areas in which E. canis is endemic.


Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis.
Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1*06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 × 10(-18)) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1*09:01, and *04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1*15:02-DQB1*06:01 and DRB1*13:02-DQB1*06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region.


Split cord malformation and neurenteric cyst--case report and a theory of embryogenesis.
A rare case of split cord malformation with neurenteric cyst is presented. The clinical, radiological and surgical findings are presented, and the possible embryological basis is discussed. To our knowledge, only seven such cases have been reported in the literature.


Trevor's Disease: A Literature Review regarding Classification, Treatment, and Prognosis apropos of a Case.
Background. Dysplasia epiphysealis hemimelica (DEH) is rare and its main characteristic is osteochondromas of the epiphysis of long bones. Methods. We report a case of DEH of the ankle in an 8-year-old boy that was resected in 2005. Additionally we collect all the reported cases of DEH. The literature is reviewed regarding the treatment, prognosis, long term function, and patterns and areas affected by DEH. Results. In our case no complications were noted and our patient remains asymptomatic. Reviewing the literature we found that 73 authors have reported 144 cases from 1926 to 2013. We propose and describe a new classification that correlates with prognosis. According to our classification DEH is classified as types 1 with single lower limb involvement, 2 with multiple lower limb, 3 with single upper limb, 4 with multiple upper limb, 5 with upper and lower limb, and 6 with spine. Conclusions. All single lesions should be followed up and if indicated a whole body nuclear bone scan can be useful in identifying the existence of multiple affected joints. Type 1 lesions have better prognosis than 2 and have less chances of developing OA even if not resected. Resection, even if partial, can be a successful treatment for DEH.


Data collection in cancer clinical trials: Too much of a good thing?
Substantial staff time and costs are incurred in the collection of data for cancer clinical trials. Anecdotal experience suggests that much of these data are never used in the analysis or reporting of a trial. To quantify data items collected in cancer clinical trials and calculate what percentage is used in subsequent published manuscripts. Cancer clinical trials completed by the Ontario Clinical Oncology Group (OCOG) between 2003 and 2012 and the corresponding primary outcome publication were identified. The number of data items collected on each trial's case report form (CRF) was counted and sorted into 18 categories including eligibility, baseline characteristics, medical history, toxicity, and recurrence. The data items were then counted within the corresponding published manuscripts to determine percent of data used overall and within each section. In all, 8 trials, with 9 corresponding publications, were evaluated. The CRF analysis revealed that the total collected items per subject ranged from 186 to 1035 per trial with a median of 599. Across all the publications, a median of 96 data items (18%) were reported in each manuscript, ranging from 11% to 27% per trial. In 8 of the 18 categories, 4% or less of collected data items were used. The number of trials reviewed is small and were conducted from a single clinical trial coordinating centre. The main outcome of the number of data items used in the published manuscript is a surrogate for trial information considered valuable by investigators. Some data may be deemed important by investigators but not included in manuscripts. In this analysis of publications from 8 clinical trials, a small amount of data collected was ultimately used in peer-reviewed journal manuscripts. A large amount of data collected in cancer trials appears to go unused and could be omitted from CRFs, thus simplifying data collection and improving trial efficiency.


[The role of oleic acid in the process of induced destruction of Escherichia coli M-17].
The influence of oleic acid on the process of the destruction of E. coli, induced by the transfer of the bacteria from the growth medium into solution without nutrient substances and their treatment with oleic acid at a temperature of 45 degrees C, was studied. Oleic acid at a concentration of 200 nmol/ml accelerated the destruction of E. coli in comparison with the control organisms, but did not lead to the significant increase of the final degree of the destruction of biomass. The dynamics of the inclusion of labeled oleic acid into E. coli cell fractions after the induction of autolysis was analyzed. The radioactive label was most actively included into the lipid (chloroform) fraction of bacterial biopolymers. Simultaneously with the destruction of some cells in the population the inclusion of labeled oleic acid into intact cells was found to occur.


Apparent diffusion coefficient of uterine leiomyoma as a predictor of the potential response to uterine artery embolization.
To determine the utility of the apparent diffusion coefficient (ADC) of uterine leiomyoma for prediction of the potential response to uterine artery embolization (UAE). This prospective study included 49 patients with uterine leiomyomas who underwent diffusion-weighted magnetic resonance (MR) imaging before UAE between May 2011 and January 2012. All patients also underwent 3-month follow-up MR imaging after UAE. Using conventional and diffusion-weighted MR imaging sequences, 72 uterine leiomyomas ≥ 3 cm were prospectively evaluated. The volume of each leiomyoma was calculated, and quantitative measurement of ADC was performed. Regression analysis was used to evaluate the relationship between ADC and volumetric response after UAE. Receiver operating characteristic curve analysis was performed to determine the sensitivity and specificity of ADC for prediction of the potential response to UAE. Interclass correlation coefficient analysis was used to assess interobserver variability between two radiologists. Volume reduction rates of leiomyomas after UAE ranged from 0.2%-89.1% (mean, 44.1%). ADC ranged from 0.559 × 10(-3) mm(2)/s to 1.814 × 10(-3) mm(2)/s (mean, 1.170 × 10(-3) mm(2)/s). ADC was statistically significantly related to volumetric response of leiomyomas (P = .014). Using a threshold of 1.092 × 10(-3) mm(2)/s, the sensitivity and specificity of ADC for prediction of > 50% volume reduction of the leiomyoma after UAE were 82.6% and 52.3%, respectively. Using a threshold of 1.023 × 10(-3) mm(2)/s, the sensitivity and specificity of ADC for prediction of < 30% volume reduction were 80.8% and 33.3%, respectively. The interclass correlation coefficient for measuring ADC of uterine leiomyomas between two radiologists was 0.98. ADC of uterine leiomyomas was significantly related to the volume reduction after UAE. ADC may be useful in predicting the potential response to UAE. A high ADC of the uterine leiomyoma may be associated with a greater volume reduction after UAE.


[On terminology of ano-rectal abscesses and fistulae].
There are different names: perianal abscesses and fistulae, periproctitis, paraproctitis, pararectal inflammatory and fistulous processes, etc. It is our opinion that the name perianal and anal fistulae does not correspond to the origin of the fistulae from an abscess of the rectal wall, although it is fairly common. To offer a name, based on the patophysiological mechanism and anatomic localization of the inflammatory process in the pararectal area through study of the origin and the way of development of ano - rectal abscesses and fistulae. A group of 430 (4%) patients with recto - perineal abscesses and fistulae has been analyzed out of a total of 10 726 hospitalized patients for the 1986 - 2005 period. Of them 241 patients (56,1 %) have been with recto - perineal fistulae, and 189 (43,9%) with recto - perineal abscesses. The process starts in the rectal wall, in the Morgan's crypts - cryptitis, after which the process transits to the perineal connective tissue. This succession in the development of the inflammatory process allows us to put the term " rectum" before "perineum" in the name adopted by us "recto - perineal abscesses and fistulae". It is our opinion that it is more appropriate to consider fistulae as a consequence from the abscesses, united in a single name recto - perineal abscesses and fistulae.


Validation of the measure of processes of care for adults: a measure of client-centred care.
To assess the psychometric properties of the measure of processes of care for adults (MPOC-A), a measure of client-centredness of care for parents of children with disabilities, adapted for adult health-care settings. A validation study. Regional orthopaedic service of a university-affiliated hospital in ON, Canada. All patients and families who had had joint replacement surgery (Knee or Hip) between January and August of 2007. MPOC-A and the client satisfaction questionnaire (CSQ). One hundred and seventy-six questionnaires filled out by patients and 81 by family members were analysed. Scales demonstrated high internal consistency (Cronbach's alpha varying from 0.81 to 0.93 for patients and from 0.88 to 0.96 for family members). MPOC-A domain scores were moderately correlated with CSQ total scores (Pearson coefficients varying from 0.44 to 0.66 for patients and from 0.53 to 0.72 for family members). Moderate to good inter-rater agreement [intraclass correlation coefficient (ICC) from 0.50 to 0.74] and high test-retest reliability were found (ICCs varying from 0.73 to 0.83 for patients and from 0.75 to 0.91 for family members). MPOC-A has demonstrated good psychometric properties. As general satisfaction scores are notoriously poor indicators of the quality of care, this measure can help us understand the elements that contribute to overall judgements of satisfaction and provide a level of understanding that is important to improve service quality and delivery.


Therapy of hepatitis C in patients with HIV infection.
Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.


Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation.
Neuronal microtubules have unique stability properties achieved through developmental regulation at the expression and posttranslational levels on tubulins and microtubule associated proteins. One of the most specialized tubulins specific for neurons is class-III beta-tubulin (also known as beta6-tubulin). Both the upregulation and the post-translational processing of class-III beta-tubulin are believed to be essential throughout neuronal differentiation. The present investigation documents the temporal and spatial patterns of class-III beta-tubulin expression throughout neurogenesis. For this study a novel polyclonal antiserum named U-beta6, specific to unphosphorylated class-III beta-tubulin has been developed, characterized and compared with its commercial homologue TuJ-1. Our experiments indicate that the two antibodies recognize different forms of class-III beta-tubulin both in vitro and in vivo. Biochemical data revealed that U-beta6 bound unphosphorylated soluble class-III beta-tubulin specifically, while TuJ-1 recognized both the phosphorylated and unphosphorylated forms of the denatured protein. In vivo U-beta6 was associated with neurogenesis and labelled newly committed CNS and PNS neuroblasts expressing neuroepithelial cytoskeletal (nestin and vimentin) and surface markers (the anti-ganglioside supernatant, A2B5 and the polysialic acid neural adhesion molecule, PSA-NCAM), as well as differentiating neurons. These studies with U-beta6 illustrate three main developmental steps in the neuronal lineage: the commitment of neuroepithelial cells to the lineage (U-beta6 +ve/TuJ-1-ve cells); a differentiation stage (U-beta6 +ve/TuJ-1 +ve cells); and, finally, neuronal maturation correlating with a drop in unphosphorylated class-III beta-tubulin immunostaining levels. These investigations also conclude that U-beta6 is an earlier marker than TuJ-1 for the neuronal lineage in vivo, and it is thus the earliest neuronal lineage marker known so far.


Managing the COVID-19 risk: the practicalities of delivering high stakes OSCEs during a pandemic.
This article was migrated. The article was marked as recommended. The impact of the COVID-19 pandemic on the teaching and assessment of clinical skills continues to pose significant challenges for healthcare education providers worldwide. In March 2020 Duke-National University of Singapore (Duke-NUS) Medical School demonstrated how to design and implement clinical skills examinations (OSCEs) in the early phase of COVID-19. As governing bodies continue to revise restrictions to help 'flatten the curve', educational institutions have to undertake a rapid review of assessment practices and adapt to this ever-changing environment. This case study describes the risk-assessments and challenges faced when delivering high stakes OSCEs during the COVID-19 pandemic. We also describe successful mitigation strategies implemented to combat these risks, and how we also embraced and leveraged technology in a very creative way despite the restrictions and constrained environment. We describe and share practical guidance that may be of help or interest to healthcare education providers across all disciplines on how to effectively deliver clinical and procedural skills examinations that are authentic, valid and comply with the strict national COVID-19 restrictions implemented during this time.


The effects of laboratory animal diets on the potency tests of bacterial vaccines.
Comparative studies of the responses elicited by mice fed on PCD and FFG diets to a number of bacterial vaccines have shown a significant reduction in the immune response to tetanus toxoid but not to Clostridium septicum toxoid and increased resistance to challenge with E. coli and syngeneic tumour cells but not to Pasteurella multocida. These differences cannot readily be explained in terms of differences between the identifiable constituents of the diets and illustrte the dangers of vaccine potency tests that require an absolute level of response to the material under test.


Analysis of influencing factors of complications after laparoscopic inguinal hernia repair: An observational study.
To explore the influencing factors of complications after laparoscopic inguinal hernia repair (LIHR). A case retrospective analysis was conducted to collect clinical data of 212 patients with inguinal hernia who underwent LIHR in our hospital from July 2020 to October 2022. The patients were followed up by telephone and subsequent visit, and the enrolled patients were divided into the complication group (n = 36) and the non-complication group (n = 176) according to the presence or absence of complications. Chi-square test was used for univariate analysis, and the data with statistical significance between groups were included in the multivariate Logistic regression analysis model to investigate the risk factors for complications associated with LIHR. Common complications in patients undergoing LIHR included seroma, hematoma, urinary retention, unexplained chronic pain, etc. Body mass index (BMI), intraoperative blood loss, medical history time, hernia sac management, intraoperative adhesions, abnormal coagulation function, recurrent hernia, and hypertension were the influencing factors for complications after LIHR (χ2 = 6.809, 13.393, 5.371, 5.775, 4.128, 5.331, 4.920, and 6.675, P < .05). Multivariate analysis showed that BMI (odd ratio [OR] = 5.201, 95% confidence interval [CI] = 0.816-6.965, P < .05), intraoperative blood loss (OR = 2.512, 95% CI = 1.712-3.689, P < .05), intraoperative adhesions (OR = 6.352, 95% CI = 0.162-6.669, P < .05), abnormal coagulation function (OR = 6.352, 95% CI = 0.162-6.669, P < .05), recurrent hernia (OR = 2.208, 95% CI = 1.415-3.446, P < .05), and hypertension (OR = 3.365, 95% CI = 0.009-6.326, P < .05) were independent risk factors for complications after LIHR (P < .05). Common complications of LIHR included seroma, hematoma, urinary retention, etc. BMI, intraoperative blood loss, intraoperative adhesions, abnormal coagulation function, recurrent hernia, and hypertension were risk factors for complications after LIHR.


Distribution of myelin basic protein messages relative to the cytoskeleton.
In situ hybridization is performed on oligodendrocytes using oligo- nucleotide probes to determine the subcellular distribution of myelin basic protein (MBP) encoding messages which are associated with the cytoskeleton, relative to sub-cellular distribution of all MBP-encoding messages in the cells.


Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats.
The aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306 g, range 251-333 g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-α and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis.


Automatic parameter selection for denoising algorithms using a no-reference measure of image content.
Across the field of inverse problems in image and video processing, nearly all algorithms have various parameters which need to be set in order to yield good results. In practice, usually the choice of such parameters is made empirically with trial and error if no "ground-truth" reference is available. Some analytical methods such as cross-validation and Stein's unbiased risk estimate (SURE) have been successfully used to set such parameters. However, these methods tend to be strongly reliant on restrictive assumptions on the noise, and also computationally heavy. In this paper, we propose a no-reference metric Q which is based upon singular value decomposition of local image gradient matrix, and provides a quantitative measure of true image content (i.e., sharpness and contrast as manifested in visually salient geometric features such as edges,) in the presence of noise and other disturbances. This measure 1) is easy to compute, 2) reacts reasonably to both blur and random noise, and 3) works well even when the noise is not Gaussian. The proposed measure is used to automatically and effectively set the parameters of two leading image denoising algorithms. Ample simulated and real data experiments support our claims. Furthermore, tests using the TID2008 database show that this measure correlates well with subjective quality evaluations for both blur and noise distortions.


[Effect of 3-oxypyridine and succinic acid derivatives on endometrial leucocyte infiltration and lipid peroxidation in recrudescence of inflammatory diseases of the uterus and its appendages].
The effect of domestic 3-oxypyridine and succinic acid derivatives (emoxipin, reamberin and mexidol) included in the complex treatment of recrudescence of inflammatory diseases of the uterus and its appendages, as manifested in endometrial leucocyte infiltration (ELI) compared to lipid peroxidation products concentration in blood serum, was assessed in a short-term, prospective placebo-controlled single-blind randomized trial. It has been found that two-week infusions of emoxipin (single dose, 150 mg), reamberin (single dose, 400 ml), and mexidol (single dose, 300 mg) favor a decrease in ELI and influence ambiguously on lipid peroxidation - antioxidant (LPA) system condition in blood serum of patients. It has been found that 3-oxypyridine derivative (emoxipin) decreases the intensity of ELI, but does not affect LPA system condition. Succinic acid derivative (reamberin) is inferior to emoxipin in the degree of decreasing ELI, but reduces the concentration of the antioxidant protein ceruloplasmin. Mexidol, being 3-oxipyridine and succinic acid derivative simultaneously, exceeds reamberin in decreasing ELI, increases concentration of blood antioxidant components (alpha-tocopherol and ceruloplasmin), and decreases the level of primary isopropanol-soluble products of lipid peroxidation.


Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage.
There are a few previously reported studies about the effect of Nigella sativa oil on renal ischemia-reperfusion injury (IRI). The aim of the present study was to test the hypothesis whether pre- or post-treatment with N. sativa hydroalcoholic extract (NSE) would reduce tissue injury and oxidative damages in a clinically relevant rat model of renal IRI. IRI was induced by clamping of bilateral renal arteries for 40 min fallowed by reperfusion for 180 min. NSE was prepared in a Soxhlet extractor and administrated with doses of 150 mg/kg or 300 mg/kg at 1 hr before ischemia induction (P-150 and 300) or at the beginning of reperfusion phase (T-150 and 300), via jugular catheter intravenously. The kidneys were then removed and subjected to biochemical analysis, comet assay or histopathological examination. The kidneys of untreated IRI rats had a higher histopathological score (P<0.001), while in P-150, as well as T-150 and T-300 groups tubular lesions significantly decreased (P<0.001). Pre- and post-treatment with NSE also resulted in a significant decrease in malondialdehyde (MDA) level (P<0.001) and DNA damage (P<0.001) that were increased by renal I/R injury. NSE treatment also significantly restore (P<0.01) the decrease in renal thiol content caused by IRI. The present study shows N. sativa extract has marked protective action against renal IRI, which may be partly due to its antioxidant effects.


Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein.
Alzheimer disease (AD) is associated with extracellular deposition of proteolytic fragments of amyloid precursor protein (APP). Although mutations in APP and proteases that mediate its processing are known to result in familial, early onset forms of AD, the mechanisms underlying the more common sporadic, yet genetically complex forms of the disease are still unclear. Four single-nucleotide polymorphisms within the ubiquilin-1 gene have been shown to be genetically associated with AD, implicating its gene product in the pathogenesis of late onset AD. However, genetic linkage between ubiquilin-1 and AD has not been confirmed in studies examining different populations. Here we show that regardless of genotype, ubiquilin-1 protein levels are significantly decreased in late onset AD patient brains, suggesting that diminished ubiquilin function may be a common denominator in AD progression. Our interrogation of putative ubiquilin-1 activities based on sequence similarities to proteins involved in cellular quality control showed that ubiquilin-1 can be biochemically defined as a bona fide molecular chaperone and that this activity is capable of preventing the aggregation of amyloid precursor protein both in vitro and in live neurons. Furthermore, we show that reduced activity of ubiquilin-1 results in augmented production of pathogenic amyloid precursor protein fragments as well as increased neuronal death. Our results support the notion that ubiquilin-1 chaperone activity is necessary to regulate the production of APP and its fragments and that diminished ubiquilin-1 levels may contribute to AD pathogenesis.


[Equally good care of myocardial infarction in Sweden today. Geographic differences in mortality are without significance for the individual patient].
It is a known fact that the 1990s brought a decrease in mortality after myocardial infarction in Sweden but that differences in mortality rates following myocardial infarction still remain between the Swedish counties. Unresolved, however, are questions as to what these inter-county differences mean for the individual patient and what role hospital care plays in this context. We analysed all patients aged 64-85 years who were hospitalised following diagnosis of myocardial infarction in Sweden during the period 1993-1996. To gain an understanding of the relevance of geographical differences in mortality after myocardial infarction for the individual patient we applied multi-level regression analysis and calculated county and hospital median odds ratios (MORs) in relation to 28-day mortality. For hospitalised patients with myocardial infarction, being cared for in another hospital with higher mortality would increase the risk of dying by 9% (MOR = l.09) in men and 12% in women. If these patients moved to another county with higher mortality the risk would increase by 7% and 3%, respectively. The small geographical differences in 28-day mortality after myocardial infarction found in Sweden suggest a high degree of equality across the country; however, further improvement could be achieved in hospital care, especially for women--an issue that deserves further analysis.


Role of Purine-Rich Regions in Mason-Pfizer Monkey Virus (MPMV) Genomic RNA Packaging and Propagation.
A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified.


A role for DNA supercoiling in the regulation of the cytochrome bd oxidase of Escherichia coli.
The cydAB operon of Escherichia coli encodes cytochrome bd, a terminal oxidase in the aerobic respiratory chain. The high oxygen affinity of this oxidase explains its increased synthesis under low-oxygen conditions. Expression of the cydAB operon is controlled by the ArcA/ArcB two-component system and the oxygen-sensing transcriptional regulator Fnr. However, cydAB expression is still induced upon entry into stationary phase or following a shift to anaerobic conditions in a mutant deleted for arcA and fnr [Cotter, P. A. & Gunsalus, R. P. (1992), FEMS Microbiol Lett 91, 31-36]. Indeed, such a mutant contains 60% of the wild-type levels of spectrally detectable cytochrome bd. A possible mechanism to account for this regulation is that changes in negative supercoiling, which occur during a shift to low-oxygen or anaerobic conditions, may contribute to the regulation of the cydAB operon. This paper reports several lines of evidence in support of this idea. Firstly, the expression of cydAB, and the final level of spectrally detectable cytochrome bd, is sensitive to inhibitors of DNA gyrase, the enzyme responsible for introducing negative supercoils into DNA. Both nalidixic acid and novobiocin reduce cydA-lacZ expression in a concentration-dependent manner. Secondly, in a gyrA mutant, defective in DNA gyrase activity, expression of cydAB is reduced to a basal level that is no longer sensitive to the oxygen status. Both gyrase inhibitors and the gyrA mutation reduce cydAB expression in a strain deleted for arcA and fnr, indicating that their effects are not mediated indirectly through ArcA or Fnr, but rather that they are likely to be direct effects on cydAB expression. In conclusion, the authors have shown that changes in DNA supercoiling play a role in the induction of cydAB expression and may provide a general way of increasing cytochrome bd levels in the cell in response to environmental stress.


Psychophysiological responses to robotic rehabilitation tasks in stroke.
This paper presents the analysis of four psychophysiological responses in post-stroke upper extremity rehabilitation. The goal was to determine which psychophysiological responses would provide the most reliable information about subjects' psychological states during rehabilitation. Heart rate, skin conductance, respiration, and skin temperature were recorded in a stroke group and a control group during two difficulty levels of a pick-and-place task performed in a virtual environment using a haptic robot and during a cognitive task. Psychophysiological measurements were correlated with results of a self-report questionnaire. All four responses showed significant changes in response to the different tasks. Skin conductance differentiated between the two difficulty levels and was correlated with self-reported arousal in both stroke and control groups. Skin temperature differentiated between the two difficulty levels for the control group, but provided poor results for the stroke group. Heart rate and respiration increased during tasks, but their connection to psychological state was unclear. Results suggest that, of the four measured responses, skin conductance offers the most potential as a psychological state indicator, with other measures providing supplementary information. Psychophysiological measurements could thus be used in closed-loop biocooperative systems that would detect the user's psychological state and change the course of therapy accordingly.


The effectiveness of two different multimodal training modes on physical performance in elderly.
The study compared the effect of 12-week multimodal training programme performed twice a week at the regular exercise facility (REF) with the 12-week multimodal training programme performed three times per week as a part of the research programme (EX). Additionally, the study analysed how the experimental training programme affect the physical performance of cognitive healthy and mild cognitive impaired elderly (MCI). The REF training group included 19 elderly (65.00±3.62 years). The experimental training programme combined cognitively healthy (EXH: n=16; 66.3±6.42 years) and age-matched individuals with MCI (EXMCI: n=14; 66.00±4.79 years). 10m maximal walking speed (10mMWS), Five Times Sit-to-Stand Test (FTSS), maximal and relative voluntary contraction (MVC & rel. MVC) were analysed. The REF group improved in 10mMWS (t=2.431, p=.026), the MVC (t=-3.528, p=.002) and relative MVC (t=3.553, p=.002). The EXH group improved in FTSS (t=5.210, P=.000), MVC (t=2.771, p=.018) and relative MVC (t=-3.793, p=.004). EXMCI improved in FTSS (t=2.936, p=.012) and MVC (t=-2.276, p=.040). According to results, both training programmes sufficiently improved walking speed and muscle strength in cognitively healthy elderly. Moreover, the experimental training programme improved muscle strength in MCI elderly.


From graphene to graphene oxide: the importance of extended topological defects.
Graphene oxide (GO) represents a complex family of materials related to graphene: easy to produce in large quantities, easy to process, and convenient to use as a basis for further functionalization, with the potential for wide-ranging applications such as in nanocomposites, electronic inks, biosensors and more. Despite their importance, the key structural traits of GO, and the impact of these traits on properties, are still poorly understood due to the inherently berthollide character of GO which complicates the establishment of clear structure/property relationships. Widely accepted structural models of GO frequently neglect the presence of extended topological defects, structural changes to the graphene basal plane that are not removed by reduction methods. Here, a combination of experimental approaches and molecular simulations demonstrate that extended topological defects are a common feature across GO and that the presence of these defects strongly influences the properties of GO. We show that these extended topological defects are produced following even controlled 'gentle' functionalization by atomic oxygen and are comparable to those obtained by a conventional modified Hummers' method. The presence of the extended topological defects is shown to play an important role in the retention of oxygen functional groups after reduction. As an exemplar of their effect on the physical properties, we show that the GO sheets display a dramatic decrease in strength and stiffness relative to graphene and, due to the presence of extended structural defects, no improvement is seen in the mechanical properties after reduction. These findings indicate the importance of extended topological defects to the structure and properties of functionalized graphene, which merits their inclusion as a key trait in simple structural models of GO.


Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG.
Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.


The importance of glutamate, glycine, and gamma-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity.
Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb.


Validation of a Food Frequency Questionnaire to Assess Intake of n-3 Polyunsaturated Fatty Acids in Switzerland.
Population-based data suggest that high intake of omega-3 (n-3) polyunsaturated fatty acids (PUFA) may be beneficial in a variety of health conditions. It is likely that mainly those patients with preexisting n-3 deficiency are those that benefit most from n-3 fatty acid supplementation. Therefore, for targeted interventions, a fast and reliable screening tool for n-3 PUFA intake is necessary. Thus, the aim of this project was to adapt and validate a food frequency questionnaire (FFQ) for n-3 PUFA intake in Switzerland while using as references the following: (1) 7-day food records (FR), and (2) n-3 fatty acid composition of red blood cells (RBC). We recruited 46 healthy adults for the first part of the study and 152 for the second. We used the dietary software EBISpro for the analysis of n-3 PUFA intake. RBC fatty acid composition was determined by gas chromatography mass spectrometry (GC-MS). Using correlation analysis, we found a moderate significant association between FFQ and FR for α-linolenic acid (ALA), eicosapentanoic acid (EPA), docosahexanoic acid (DHA), and total n-3 fatty acids (all r between 0.523 and 0.586, all p < 0.001). Bland Altman analysis further showed good agreement between the two methods and no proportional bias. Correlations between FFQ and RBC fatty acid composition were also moderate for EPA and DHA (r = 0.430 and r = 0.605, p < 0.001), but weaker for ALA and total n-3 (r = 0.314 and r = 0.211, p < 0.01). The efficacy of the FFQ to classify individuals into the same or adjacent quartile of RBC PUFA content ranged between 70% and 87% for the different fatty acids. In conclusion, we showed that the Swiss n-3 PUFA FFQ is a valid tool to assess dietary n-3 PUFA intake, especially DHA and EPA, to determine population groups at risk for low intake.


Socioeconomic patterns in the use of public and private health services and equity in health care.
Several studies in wealthy countries suggest that utilization of GP and hospital services, after adjusting for health care need, is equitable or pro-poor, whereas specialist care tends to favour the better off. Horizontal equity in these studies has not been evaluated appropriately, since the use of healthcare services is analysed without distinguishing between public and private services. The purpose of this study is to estimate the relation between socioeconomic position and health services use to determine whether the findings are compatible with the attainment of horizontal equity: equal use of public healthcare services for equal need. Data from a sample of 18,837 Spanish subjects were analysed to calculate the percentage of use of public and private general practitioner (GP), specialist and hospital care according to three indicators of socioeconomic position: educational level, social class and income. The percentage ratio was used to estimate the magnitude of the relation between each measure of socioeconomic position and the use of each health service. After adjusting for age, sex and number of chronic diseases, a gradient was observed in the magnitude of the percentage ratio for public GP visits and hospitalisation: persons in the lowest socioeconomic position were 61-88% more likely to visit public GPs and 39-57% more likely to use public hospitalisation than those in the highest socioeconomic position. In general, the percentage ratio did not show significant socioeconomic differences in the use of public sector specialists. The magnitude of the percentage ratio in the use of the three private services also showed a socioeconomic gradient, but in exactly the opposite direction of the gradient observed in the public services. These findings show inequity in GP visits and hospitalisations, favouring the lower socioeconomic groups, and equity in the use of the specialist physician. These inequities could represent an overuse of public healthcare services or could be due to the fact that persons in high socioeconomic positions choose to use private health services.


Exploring the motivations for rural tourism in China during the COVID-19: The existence of a single motivation.
The COVID-19 epidemic had an appropriate impact on tourists' trip psychology and their subsequent behavior in participating in rural tourism activities. The purpose of this paper is to explore the types of motivations Chinese tourists have for participating in rural tourism in the context of COVID-19, and to comparatively analyze the similarities and differences in motivations for rural tourism during the epidemic and in normal times. An interpretive paradigm qualitative data collection method was used: semi-structured interviews and focus group discussions. Respondents were 21 tourists, who were selected through purposive and snowball sampling. Through content analysis, we found that rural tourism motivations during the epidemic included both diversified and singular motivations. The pull effect of rural destinations is related to distance and ease of realization. For rural areas in close proximity, a single motivation is sufficient to drive tourists. In addition, we found that there was no "altruistic motivation" for rural tourism during the COVID-19 period, but "altruistic feelings" for the preservation of ancient villages were generated during rural tourism. Finally, we discuss the theoretical and practical significance of this study and make suggestions for future research. The study explains tourists' companionship preferences, activity choices, and affective changes, and provides a basis for the operation and advertising strategies of rural destinations to attract tourists and promote their sustainable development.


[Neocystoplasty after pelvic evisceration on the subject of colorectal cancer].
The experience of 104 total pelvic eviscerations, 78 operations on the reason of locally advanced colorectal cancer, was analyzed. The reconstructive stage included urine reservoir formation in all cases. Different organs were used for the purpose. Early postoperative complications were registered in 74,3% of patients. Postoperative death rate was 8,9%, in majority of cases as a reason of the anastomotic insufficiency. Of the recovered patients, 48 survived 1 year after the operation, 16 patients showed the 3 years survival and 6 patients had lived more then 5 years.


An update on physician practice cost shares.
The 1988 physicians' practice costs and income survey (PPCIS) collected detailed costs, revenues, and incomes data for a sample of 3,086 physicians. These data are utilized to update the Health Care Financing Administration (HCFA) cost shares used in calculating the medicare economic index (MEI) and the geographic practice cost index (GPCI). Cost shares were calculated for the national sample, for 16 specialty groupings, for urban and rural areas, and for 9 census divisions. Although statistical tests reveal that cost shares differ across specialties and geographic areas, sensitivity analysis shows that these differences are small enough to have trivial effects in computing the MEI and GPCI. These results may inform policymakers on one aspect of the larger issue of whether physician payments should vary by geographic location or specialty.


The role of eye movements in a contour detection task.
Vision combines local feature integration with active viewing processes, such as eye movements, to perceive complex visual scenes. However, it is still unclear how these processes interact and support each other. Here, we investigated how the dynamics of saccadic eye movements interact with contour integration, focusing on situations in which contours are difficult to find or even absent. We recorded observers' eye movements while they searched for a contour embedded in a background of randomly oriented elements. Task difficulty was manipulated by varying the contour's path angle. An association field model of contour integration was employed to predict potential saccade targets by identifying stimulus locations with high contour salience. We found that the number and duration of fixations increased with the increasing path angle of the contour. In addition, fixation duration increased over the course of a trial, and the time course of saccade amplitude depended on the percept of observers. Model fitting revealed that saccades fully compensate for the reduced saliency of peripheral contour targets. Importantly, our model predicted fixation locations to a considerable degree, indicating that observers fixated collinear elements. These results show that contour integration actively guides eye movements and determines their spatial and temporal parameters.


ViTab Transformer Framework for Predicting Induced Electric Field and Focality in Transcranial Magnetic Stimulation.
Transcranial magnetic stimulation is an electromagnetic induction-based non-invasive therapeutic technique for neurological diseases. For finding new clinical applications and enhancing the efficacy of TMS in existing neurological disorders, the current study focuses on a deep learning-based prediction model as an alternative to time-consuming electromagnetic (EM) simulation software. The main bottleneck of the existing prediction models is to consider very few input parameters of a standard coil such as coil type and coil position for predicting an output of electric field value. To overcome this limitation, a transformer-based prediction model titled as ViTab transformer is developed in this work to predict electric field (E-max), focality or area of stmulation (S-half), and volume of stimulation (V-half) by considering several input parameters such as sources of MRI images, types of coils, coil position, rate of change of current, brain tissues conductivity, and coil distance from the scalp. The proposed framework consists of a vision and a tab transformer to handle both image and tabular-type data. The prediction performance of the offered model is evaluated in terms of coefficient determination, R2 score, for E-max, V-half, and S-half in the testing phase. The obtained result in terms of R2 score for E-max, V-half, and S-half are found 0.97, 0.87, and 0.90 respectively. The results indicate that the suggested ViTab transformer model can predict electric field as well as focality more accurately than the current state-of-the-art methods. The reduced computational time, as well as efficient prediction accuracy, resembles that ViTab transformer can assist the neuroscientist and neurosurgeon prior to providing superior TMS treatment in near future.


Structural and topographical studies of the type IV bundle-forming pilus assembly complex of enteropathogenic Escherichia coli.
The type IV bundle-forming pili (BFP) of enteropathogenic Escherichia coli (EPEC) are required for virulence in orally challenged human volunteers and for the localized adherence and autoaggregation in vitro phenotypes. BFP filament biogenesis and function are encoded by the 14-gene bfp operon. The BFP assembly complex, containing a BfpB-His6 fusion protein, was chemically cross-linked in situ, and the complex was then purified from BFP-expressing EPEC by a combination of nickel- and BfpB antibody-based affinity chromatography. Characterization of the isolated complex by immunoblotting using BFP protein-specific antibodies showed that at least 10 of the 14 proteins specified by the bfp operon physically interact to form an oligomeric complex. Proteins localized to the outer membrane, inner membrane, and periplasm are within this complex, thus demonstrating that the complex spans the periplasmic space. A combination of immunofluorescence and immuno-gold thin-section transmission electron microscopy studies localized this complex to one pole of the cell.


Effects of zero magnetic field on the conformation of chromatin in human cells.
The effects of zero magnetic field on human VH-10 fibroblasts and lymphocytes were studied by the method of anomalous viscosity time dependencies (AVTD). A decrease of about 20% in the AVTD peaks was observed within 40 to 80 min of exposure of fibroblasts. This decrease was transient and disappeared 120 min after beginning of exposure. Similar kinetics for the effect of zero field was observed when cells were exposed 20 min and then kept at an ambient field. A 20% decrease of the AVTD peaks (p < 0.005 to 0.05) 40 to 70 min after 20 min exposure to zero field was reproduced in four independent experiments (out of four) with human lymphocytes from the same healthy donor. Contrary to the effects of zero field, irradiation of lymphocytes or fibroblasts with gamma-rays resulted in significant increase of the AVTD peaks immediately after irradiation. We concluded that zero field and gamma-rays caused hypercondensation and decondensation of chromatin, correspondingly. The effect of ethidium bromide served as a positive control and supported this conclusion. The effects of zero field on human lymphocytes were more significant in the beginning of G1-phase than in G0-phase. Thus, human fibroblasts and lymphocytes were shown to respond to zero magnetic field.


Impact of active and passive social facilitation on self-paced endurance and sprint exercise: encouragement augments performance and motivation to exercise.
The positive effect of an audience on performance is anecdotally well known, but the impact of such social facilitation to both performance and the motivation to exercise have not been thoroughly explored. The aim of this study was therefore to investigate verbal encouragement as a means to promote positive behavioural adherence to exercise and augmented performance. Twelve untrained but active individuals (seven female), age 24±3 years participated in this study. Exercise conditions with external verbal encouragement (EVE) and without external verbal encouragement (WEVE) were compared in both endurance (20 min) and sprint (2 × 30 s Wingate) cycling tasks in a randomised crossover design. Results were analysed by separate 2 (EVE/WEVE) × 2 (sprint/endurance) within-subjects analyses of variance for each dependent variable. Statistical significance was set at p≤0.05. EVE resulted in a significant increase, F(1,11)=15.37, p=0.002, ηp2=0.58 in the average power generated by participants in each exercise bout on the cycle ergometer. EVE also had a significant effect on reported motivation to exercise the next day, F(1,11)=5.5, p=0.04, ηp2 =0.33, which did not differ between type of exercise. External encouragement in both sprint and endurance activities resulted in large improvements in performance and motivation to continue an exercise regimen the next day, which has important implications for health, adherence and maximising physical performance using a practical intervention.


"Wet Voice" as a predictor of penetration and aspiration in oropharyngeal dysphagia.
This article describes the results of a study that investigated how well wet phonation can predict penetration and/or aspiration of ingested material in dysphagic patients. Voice samples of 23 subjects with neurologic oropharyngeal dysphagia were collected immediately after each subject had swallowed nine different boluses on videofluoroscopy. The boluses were graded according to three different consistencies and three different sizes. The presence of wetness in the voice was analyzed in relation to any ingested material that remained in the larynx or trachea after each bolus was swallowed. Results showed that there was no association between the presence of a wet voice and penetration or aspiration of prandial material after a swallow. The importance of detecting wet phonation by itself was therefore not considered diagnostic in detecting prandial penetration/aspiration by the bedside, but a wet voice may still be useful in identifying those with dysphagia who may have laryngeal dysfunction and therefore may be at risk of penetrating/aspirating any type of material, not just prandial material.


Sperm selection based on motility in polyvinylpyrrolidone is associated with successful pregnancy and embryo development.
The aim of this study was to investigate whether spermatozoon motility in polyvinylpyrrolidone (PVP) is associated with better embryo development and pregnancy rates in ICSI cycles. A total of 123 primary ICSI treatment cycles were included in this study. Semen samples were tested for motility before ICSI procedure in PVP. Within 3 min, the presence or absence of motility was recorded. Sperm functions were examined by the aniline blue (AB) chromatin condensation test and the hypoosmotic swelling test, and the chromatin stability was evaluated by inducing its decondensation with sodium dodecyl sulphate and ethylenediaminetetraacetic acid (EDTA). Fertilisation and embryo scoring were evaluated. Fifty (64%) of 78 women conceived in the PVP (+) group; and 12 (26%) of 45 women conceived in the PVP (-) group; the pregnancy rate was significantly higher in the PVP (+) group (P = 0.003). Semen parameters were observed to be similar in both groups. The mean number of total embryos obtained in ICSI procedure and transferred grade 1 embryos were significantly higher in PVP (+) group (P = 0.01 and P = 0.003 respectively). The presence of sperm motility in PVP is associated with increased pregnancy rate, higher percentage of good quality embryos, sperm chromatin condensation and decondensation.


Ethyl cellulose as a potential sustained release coating for oral pharmaceuticals.
This current study was motivated, and designed in an attempt to determine the possible application of the inert, pH-insensitive, ethyl cellulose polymer as a potential sustained-release coating for oral pharmaceuticals. Coating was effected using two relatively recent techniques, namely microencapsulation by phase separation coacervation, induced by temperature change, and drug entrapment by flocculation, induced by nonsolbent addition. Chloramphenicol was used as a model drug. Results of this study revealed the fact that ethyl cellulose proved to be a potential sustained-release coating for oral dosage forms. Moreover, the effect of the coating/core ratio was exhibited both qualitatively and quantitatively. This finding could help in the design of programmed or timed-release drugs. Accordingly, this study could be considered a successful attempt towards the utlization of ethyl cellulose in of the design of sustained-release oral pharmaceuticals.


Intelligent Imaging: Anatomy of Machine Learning and Deep Learning.
The emergence of artificial intelligence (AI) in nuclear medicine and radiology has been accompanied by AI commentators and experts predicting that AI would make radiologists, in particular, extinct. More realistic perspectives suggest significant changes will occur in medical practice. There is no escaping the disruptive technology associated with AI, neural networks, and deep learning, the most significant perhaps since the early days of Roentgen, Becquerel, and Curie. AI is an omen, but it need not be foreshadowing a negative event; rather, it is heralding great opportunity. The key to sustainability lies not in resisting AI but in having a deep understanding and exploiting the capabilities of AI in nuclear medicine while mastering those capabilities unique to the human resources.


The patient portal and abnormal test results: An exploratory study of patient experiences.
Many health care institutions are implementing patient portals that allow patients to track and maintain their personal health information, mostly in response to the Health Information Technology for Economic and Clinical Health Act requirements. Test results review is an area of high interest to patients and provides an opportunity to foster their involvement in preventing abnormal test results from being overlooked, a common patient safety concern. However, little is known about how patients engage with portals to review abnormal results and which strategies could facilitate that interaction in order to ensure safe follow-up on abnormalities. The objective of this qualitative study was to explore patients' experiences related to abnormal test result notifications through patient portals. The authors conducted semi-structured telephone interviews with 13 participants, patients and primary caregivers, between February 2014 and October 2014. Using content analysis, the authors explored patient experiences accessing abnormal test results through their portals. Respondents strongly favored access to all types of abnormal test results, but they raised several concerns including need for more timely notification and not being able to interpret the exact relevance of the result. Respondents' personal experiences with physicians, test result notification, and the portal heavily influenced respondents' notification preferences. Patient experiences with portals could be improved by development of strategies to help patients understand and manage the information received. These findings suggest important considerations for health professionals and institutions aiming to better engage patients in follow-up of their test results.


Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy.
Cardiomyopathy caused by A-type lamins gene (LMNA) mutations (LMNA cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. LMNA cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the progression of LMNA cardiomyopathy, we studied the role of calcium homeostasis in the evolution of this disease. We showed that sarcolipin, an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ ATPase (SERCA) was abnormally elevated in the ventricular cardiomyocytes of mutated mice compared with wild type mice, leading to an alteration of calcium handling. This occurs early in the progression of the disease, when the left ventricular function was not altered. We further demonstrated that down regulation of sarcolipin using adeno-associated virus (AAV) 9-mediated RNA interference delays cardiac dysfunction in mouse model of LMNA cardiomyopathy. These results showed a novel role for sarcolipin on calcium homeostasis in heart and open perspectives for future therapeutic interventions to LMNA cardiomyopathy.


[Combined treatment of patients with nephrolithiasis complicated with secondary pyelonephritis].
A total of 151 patients with nephrolithiasis participated in the study of efficacy and safety of the drug prolit cepto in conservative treatment of nephrolithiasis patients, preoperative preparation and in postoperative period after extracorporeal shock-wave lithotripsy (EC-SWL) or nephrolitholapaxy. It was found that combined treatment of nephrolithiasis complicated by secondary pyelonephritis with addition of prolit cepto raises efficacy in management of inflammation due to a positive action on microcirculation and urine bacteria. Administration of prolit cepto in nephrolithiasis patients exposed to EC-SWL or nephrolitholapaxy reduces the risk of infectious and inflammatory complications, has a nephroprotective effect and improves the course of postoperative period.


Impact of Sensor Misplacement on Dynamic Time Warping Based Human Activity Recognition using Wearable Computers.
Daily living activity monitoring is important for early detection of the onset of many diseases and for improving quality of life especially in elderly. A wireless wearable network of inertial sensor nodes can be used to observe daily motions. Continuous stream of data generated by these sensor networks can be used to recognize the movements of interest. Dynamic Time Warping (DTW) is a widely used signal processing method for time-series pattern matching because of its robustness to variations in time and speed as opposed to other template matching methods. Despite this flexibility, for the application of activity recognition, DTW can only find the similarity between the template of a movement and the incoming samples, when the location and orientation of the sensor remains unchanged. Due to this restriction, small sensor misplacements can lead to a decrease in the classification accuracy. In this work, we adopt DTW distance as a feature for real-time detection of human daily activities like sit to stand in the presence of sensor misplacement. To measure this performance of DTW, we need to create a large number of sensor configurations while the sensors are rotated or misplaced. Creating a large number of closely spaced sensors is impractical. To address this problem, we use the marker based optical motion capture system and generate simulated inertial sensor data for different locations and orientations on the body. We study the performance of the DTW under these conditions to determine the worst-case sensor location variations that the algorithm can accommodate.


TCR antagonism by peptide requires high TCR expression.
Current models of T cell activation focus on the kinetics of TCR-ligand interactions as the central parameter governing T cell responsiveness. However, these kinetic parameters do not adequately predict all T cell behavior, particularly the response to antagonist ligands. Recent studies have demonstrated that TCR number is a critical parameter influencing the responses of CD4(+) T cells to weak agonist ligands, and receptor density represents an important means of regulating tissue responsiveness in other receptor ligand systems. To systematically address the impact of TCR expression on CD8(+) T cell responses, mAbs to the TCR alpha-chain and T cells expressing two TCR species were used as two different methods to manipulate the number of available TCRs on P14 and OT-I transgenic T cells. Both methods of TCR reduction demonstrated that the efficacy of antagonist peptides was significantly reduced on T cells bearing low numbers of available receptors. In addition, the ability of weak agonists to induce proliferation was critically dependent on the availability of high numbers of TCRs. Therefore, in this report we show that TCR density is a major determinant of CD8(+) T cell reactivity to weak agonist and antagonist ligands but not agonist ligands.


Interaction of West Nile virus with primary murine macrophages: role of cell activation and receptors for antibody and complement.
We have measured growth of West Nile virus in mouse primary peritoneal macrophages (resident, thioglycolate elicited, and Mycobacterium bovis BCG activated) and in macrophagelike (P338D1) and nonmacrophage (L929, PS clone D) cell lines infected in the absence or presence of specific antibodies (immunoglobulin G ([IgG], IgM), and complement. Monoclonal antibodies directed against Fc receptors (IgG1/2b, 2.4G2) and type 3 complement receptors (Mac-1) were used to define the role of each receptor. Virus yield depended on a balance between enhancement and neutralization and was influenced by the physiologic state of the macrophage, the receptor pathway of viral entry, the mouse strain and age of donor. BCG-activated macrophages displayed a greater ability to restrict West Nile virus than nonactivated cells only in the presence of antiviral IgM, with or without complement; the Fc receptors for various classes of IgG mediated striking enhancement. These studies identify some of the complex innate and acquired factors that determine the interaction between West Nile virus and primary macrophages in vitro.


Effect of female genital cutting performed by health care professionals on labor complications in Egyptian women: a prospective cohort study.
To examine the effect of the degree of female genital cutting (FGC) performed by health-care professionals on perineal scarring; delivery mode; duration of second stage of labor; incidence of perineal tears and episiotomy in a cohort of uncircumcised versus circumcised (types I and II) women. A prospective cohort study included 450 primigravida women in active labor attending the Faculty of Medicine Cairo University Hospital between January 2013 and August 2014. Women were divided into three groups based on medical examination upon admission. Group I (Control) included 150 uncut women, Group II included 150 women with type I FGC and Group III included 150 women with type II FGC. A structured questionnaire elicited the information on women's socio-demographic characteristics including age, residence, occupation, educational level, age of marriage and FGC circumstances. Association between FGC and labor complications was examined. risk of perineal scarring; delivery mode; duration of second stage of labor; incidence of perineal tears and episiotomy. Family history of genitally cut mother/sister was the most significant socio-demographic factor associated with FGC. FGC especially type II was associated with significantly higher incidence of vulvar scar (P<0.0002), perineal tears (P<0.0001) and increased likelihood of additional vaginal and perineal trauma [odds ratio (OR): 1.85, 95% CI: 0.60-5.65. P≤0.001]. There was insignificant difference in risks of cesarean section (CS), instrumental delivery, episiotomy and short-term neonatal outcomes. The study strengthens the evidence that FGC increases the risk of tears in spite of medicalization of the practice.


Kynurenine is an endothelium-derived relaxing factor produced during inflammation.
Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. Infection of mice with malarial parasites (Plasmodium berghei) or induction of endotoxemia in mice led to endothelial expression of Ido, decreased plasma tryptophan concentration, increased kynurenine concentration and hypotension. Pharmacological inhibition of Ido increased blood pressure in systemically inflamed mice but not in mice deficient in Ido or interferon-gamma, which is required for Ido induction. Both tryptophan and kynurenine dilated preconstricted porcine coronary arteries; the dilating effect of tryptophan required the presence of active Ido and an intact endothelium, whereas the effect of kynurenine was endothelium independent. The arterial relaxation induced by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase pathways. Kynurenine administration decreased blood pressure in a dose-dependent manner in spontaneously hypertensive rats. Our results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone.


Paired comparison of apheresis platelet function after storage in two containers.
Platelet quality after storage strongly depends on the pre-storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLX and Delmed DPL-110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO(2) concentrations in the CLX bags. At day 5 there were significantly higher lactate concentrations, pO(2) levels, and aggregation after stimulation in the CLX group, while the glucose and pCO(2) concentrations were significantly lower in these platelet concentrates as compared to the DPL-110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5-day storage of platelet concentrates.


[Relationship between brain amyloid deposition and instrumental activities of daily living in older individuals: two analyses from the MAPT study].
The biomarkers of Alzheimer's disease (AD) have enabled the identification of its pathological features, many years before the onset of clinical symptoms. Positon emission tomography (PET) using radiotracers binding the amyloid plaques has, indeed, paved the way for new perspectives. However, these biomarkers have only been studies in small populations so far, with limited follow-up. The objectives of this work were to assess the interest of amyloid PET in elderly but also to study the relationship of amyloid deposition to Instrumental Activities of Daily Living (IADL) performance. Our population included 271 participants from the MAPT trial aged 70 and over, without major cognitive impairment, who performed amyloid PET examination. In a cross-sectional study we examined the association between brain amyloid load and IADL abilities. Moreover, in a longitudinal analysis, we studied the changes in IADL performance between amyloid positive and amyloid negative participants over the 3-year follow-up without and with adjustments for confounding factors (age, randomization group, ApoE genotyping, timespan between baseline and PET examination). Amyloid positive subjects showed poorer abilities in IADL compared to their amyloid negative counterparts, despite similar cognitive performance. Brain amyloid load also impacted the daily functioning of individuals over time, taking in consideration confounding factors. The difference after 3 years between the amyloid positive and negative participants was not significant (p=0.08; in adjusted models p=0.06). Amyloid negative individuals also improved in memory-related instrumental activities (p<0.001) throughout the study, unlike amyloid positive participants. These findings confirmed the relationship of brain amyloid deposition with subtle changes in IADL abilities, even in the absence of cognitive impairment. Yet, the absence of disease modifying agents as well as uncertainties regarding the long-term evolution of asymptomatic individuals showing a positive biomarker are still to be determined.


Deciphering Chemical Mediators Regulating Specialized Metabolism in a Symbiotic Cyanobacterium.
Genomes of cyanobacteria feature a variety of cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting the discovery and exploitation of the metabolic dark matter are not well understood. Here we describe the discovery of two cell density-dependent chemical mediators, nostoclide and nostovalerolactone, in the symbiotic model strain Nostoc punctiforme, and demonstrate their pronounced impact on the regulation of specialized metabolism. Through transcriptional, bioinformatic and labeling studies we assigned two adjacent biosynthetic gene clusters to the biosynthesis of the two polyketide mediators. Our findings provide insight into the orchestration of specialized metabolite production and give lessons for the genomic mining and high-titer production of cyanobacterial bioactive compounds.


Size and Quality of Drawings Made by Adults Under Visual and Haptic Control.
The aim of this study was twofold. First, our objective was to test the influence of an object's actual size (size rank) on the drawn size of the depicted object. We tested the canonical size effect (i.e., drawing objects larger in the physical world as larger) in four drawing conditions - two perceptual conditions (blindfolded or sighted) crossed with two materials (paper or special foil for producing embossed drawings). Second, we investigated whether drawing quality (we analysed both the local and global criteria of quality) depends on drawing conditions. We predicted that drawing quality, unlike drawing size, would vary according to drawing conditions - namely, being higher when foil than paper was used for drawing production in the blindfolded condition. We tested these hypotheses with young adults who repeatedly drew eight different familiar objects (differentiated by size in the real world) in four drawing conditions. As expected, drawn size increased linearly with increasing size rank, whatever the drawing condition, thus replicating the canonical size effect and showing that this effect was not dependent on drawing conditions. In line with our hypothesis, in the blindfolded condition drawing quality was better when foil rather than paper was used, suggesting a benefit from haptic feedback on the trace produced. Besides, the quality of drawings produced was still higher in the sighted than the blindfolded condition. In conclusion, canonical size is present under different drawing conditions regardless of whether sight is involved or not, while perceptual control increases drawing quality in adults.


What is the potential role of hepatic arterial infusion chemo-therapy in the current armamentorium against colorectal cancer.
The management of colorectal cancer patients with liver metastases is a common clinical problem. If patients can undergo resection of liver metastases, long-term survival can be achieved. Converting a patient from unresectable to resectable, however, remains a major challenge. The majority of patients who undergo liver resection for colorectal metastases recur; therefore, adjuvant treatment following resection should be considered. Emerging literature suggests that hepatic arterial infusion (HAI) can be combined with systemic chemotherapy. Both therapies can be given at nearly full doses, thus improving resectability and outcomes for patients with colorectal liver metastases. HAI plus systemic can also be a useful option for adjuvant treatment after hepatic resection.


Associativity and normative credal probability.
Cox's Theorem is a widely cited motivation for probabilistic models of uncertain belief. The theorem relates the associativity of the logical connectives to that of the arithmetic operations of probability. Recent questions about the correctness of Cox's Theorem have been resolved, but there are new questions about one functional equation used by Cox in 1946. This equation is missing from his later work. Advances in knowledge since 1946 and changes in Cox's research interests explain the equation's disappearance. Other associativity-based motivations avoid functional equations altogether, and so may be more transparently applied to finite domains and discrete beliefs. A discrete counterpart of Cox's Theorem can be assembled from results that have been in the literature since 1959.


Prevalence of herpes and respiratory viruses in induced sputum among hospitalized children with non typical bacterial community-acquired pneumonia.
Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance. Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed. High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control. With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.


Inclusion of Oat Polar Lipids in a Solid Breakfast Improves Glucose Tolerance, Triglyceridemia, and Gut Hormone Responses Postprandially and after a Standardized Second Meal: A Randomized Crossover Study in Healthy Subjects.
Previously, it has been indicated that oat polar lipids included in a liquid meal may have the potential to beneficially modulate various cardiometabolic variables. The purpose of this study was to evaluate the effects of oat polar lipids in a solid food matrix on acute and second meal glucose tolerance, blood lipids, and concentrations of gut-derived hormones. The oat polar lipids were consumed at breakfast and effects on the biomarkers were investigated in the postprandial period and following a standardized lunch. Twenty young, healthy subjects consumed in total four different breakfast meals in a crossover study design. The breakfasts consisted of 1. White wheat bread (WWB) with an added 7.5 g of oat polar lipids (PLL); 2. WWB with an added 15 g of oat polar lipids (PLH); 3. WWB with and added 16.6 g of rapeseed oil (RSO) as a representative of commonly consumed oils; and 4. WWB consumed alone, included as a reference. All products with added lipids contained equivalent amounts of fat (16.6 g) and available carbohydrates (50 g). Rapeseed oil was added to the oat polar lipid meals to equal 16.6 g of total fat. The standardized lunch was composed of WWB and meatballs and was served 3.5 h after the breakfast. Test variables (blood glucose, serum insulin, triglyceride (TG), free fatty acids (FFA), ghrelin, GLP-1, PYY, and GIP) were measured at fasting and repeatedly during the 5.5 h after ingestion of the breakfast. After breakfast, PLH substantially lowered postprandial glucose and insulin responses (iAUC 0-120 min) compared with RSO and WWB (p < 0.05). Furthermore, a reduced glycaemic response to lunch (210-330 min) was observed following the PLH breakfast compared to all of the other breakfasts served (p < 0.05). Oat polar lipids (PLH) significantly reduced TG and ghrelin and increased circulating gut hormones GLP-1 and PYY compared to RSO (p < 0.05). The results show that exchanging part of the dietary lipids with oat polar lipids has the potential to improve postprandial blood glucose regulation and gut hormones and thus may have a preventive effect against type 2 diabetes.


Muscle Characteristics in Pediatric Hereditary Spastic Paraplegia vs. Bilateral Spastic Cerebral Palsy: An Exploratory Study.
Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9-17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP (p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass (p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups.


In situ ground water denitrification in stratified, permeable soils underlying riparian wetlands.
The ground water denitrification capacity of riparian zones in deep soils, where substantial ground water can flow through low-gradient stratified sediments, may affect watershed nitrogen export. We hypothesized that the vertical pattern of ground water denitrification in riparian hydric soils varies with geomorphic setting and follows expected subsurface carbon distribution (i.e., abrupt decline with depth in glacial outwash vs. negligible decline with depth in alluvium). We measured in situ ground water denitrification rates at three depths (65, 150, and 300 cm) within hydric soils at four riparian sites (two per setting) using a 15N-enriched nitrate "push-pull" method. No significant difference was found in the pattern and magnitude of denitrification when grouping sites by setting. At three sites there was no significant difference in denitrification among depths. Correlations of site characteristics with denitrification varied with depth. At 65 cm, ground water denitrification correlated with variables associated with the surface ecosystem (temperature, dissolved organic carbon). At deeper depths, rates were significantly higher closer to the stream where the subsoil often contains organically enriched deposits that indicate fluvial geomorphic processes. Mean rates ranged from 30 to 120 microg N kg(-1) d(-1) within 10 m versus <1 to 40 microg N kg(-1) d(-1) at >30 m from the stream. High denitrification rates observed in hydric soils, down to 3 m within 10 m of the stream in both alluvial and glacial outwash settings, argue for the importance of both settings in evaluating the significance of riparian wetlands in catchment-scale N dynamics.


Comparison of maternal and newborn serologic tests for syphilis.
To compare the cord blood, newborn serum, and maternal serum for the diagnosis of congenital syphilis. Retrospective chart review. Kings County Hospital Center, Brooklyn, NY. Three hundred forty-eight mother-newborn pairs with positive syphilis serology. One hundred fifteen newborns (33%) had rapid plasma reagin tests of cord blood that were nonreactive. Their mothers had positive serologic findings. There were 10% false-positive cord blood samples (cord blood rapid plasma reagin tests reactive, newborn serum rapid plasma reagin tests nonreactive) and 5% false-negative cord blood samples (cord rapid plasma reagin tests nonreactive, newborn serum rapid plasma reagin tests reactive). Thirty-three newborns had congenital syphilis. Seven newborns had cord titers fourfold higher than their mothers'; only four of these newborns had congenital syphilis. Maternal serology is superior to cord blood analysis for identifying newborns at risk of congenital syphilis.


Application of SOS umu-test for the detection of genotoxic volatile chemicals and air pollutants.
The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner. These results indicate that the SOS umu-test is potentially useful for the in situ detection of genotoxic agents in occupational settings.


Androgenic and estrogenic metabolites in serum of mice fed dehydroepiandrosterone: relationship to antihyperglycemic effects.
The steroid prehormone, dehydroepiandrosterone (DHEA) has potent antihyperglycemic effects when fed in the diet of genetically diabetic C57BL/KsJ-db/db mice. The purpose of this investigation was to analyze changes in sex steroid levels in serum of mice fed DHEA, and to compare the antihyperglycemic potencies of the various metabolites in order to clarify the mechanism of DHEA action. Steroid radioimmunoassays showed that dietary DHEA entered the blood in high concentrations and was actively metabolized to both androgens (testosterone, T; dihydrotestosterone, DHT) and estrogens (estrone, E1; 17 beta-estradiol, E2). This metabolism did not require intact adrenal glands or gonads. In C57BL/KsJ normal (+/+) males, conversion of DHEA to androgens was the prominent feature; in db/db males, DHEA feeding not only increased serum T and DHT, but also serum E1 and E2 levels. The db/db mice had increased amounts of adipose tissue that sequestered more intravenously injected 3H-E2; this additional body fat could account for increased aromatization of DHEA-derived estrogen precursors. Comparisons of the relative antihyperglycemic potencies of androgenic and estrogenic steroid metabolites of DHEA in db/db mice showed that the estrogens and metabolites with estrogenic properties (androstenediol) or those convertible to estrogens (DHEA sulfate) were the most potent. Although 17 beta-E2 was effective by injection or per os, DHEA was effective only when administered per os, implicating alimentary tract conversion of DHEA to more biologically active reactants. Based on the pivotal position of DHEA as a prehormone for androgens, estrogens, and etiocholanolones, an explanation of the seemingly paradoxical effects exerted by this compound in blocking autoimmune disease, hyperglycemia, obesity, and neoplasia was proposed.


Antimicrobial constituents of the leaves of Mikania micrantha H. B. K.
To isolate plant-derived compounds with antimicrobial activity from the leaves of Mikania micrantha, to determine the compounds configuration, and to evaluate their antimicrobial activity against eight plant pathogenic fungi (Exserohilum turcicum, Colletotrichum lagenarium, Pseudoperonispora cubensis, Botrytis cirerea, Rhizoctonia solani, Phytophthora parasitica, Fusarium solani, and Pythium aphanidermatum,) and four plant pathogenic bacteria (gram negative bacteria: Ralstonia dolaanacearum, Xanthomonas oryzae pv. Oryzae, Xanthomonas Campestris pv. Vesicatoria, and Xanthomonas campestris pv. Citri), and four bacteria (gram positive bacteria: Staphyloccocus aureus, Bacillus subtilis, Micrococcus luteus, and Bacillus cereus). Antimicrobial constituents of the leaves of M. micrantha were isolated using bioactivity- guided fractionation. The antifungal activity of the isolated compounds was evaluated by the inhibit hypha growth method and inhibit spore germination method. Characterization of antibacterial activity was carried out using the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs). MIC and MBC were determined by the broth microdilution method. Six compounds - deoxymikanolide, scandenolide, dihydroscandenolide, mikanolide, dihydromikanolide, and m - methoxy benzoic acid - have been isolated from leaves of Mikania micrantha H. B. K. Deoxymikanolide, scandenolide, and dihydroscandenolide were new compounds. The result of bioassay showed that all of isolated compounds were effective against tested strains and deoxymikanolide showed the strongest activity. The leaves of M. micrantha may be a promising source in the search for new antimicrobial drugs due to its efficacy and the broadest range. Meanwhile, adverse impact of M. micrantha will be eliminated.


Effect of biosynthetic chicken growth hormone on egg production in White Leghorn hens.
Two studies were conducted to determine if injection of recombinant chicken growth hormone (cGH) influences egg production parameters in older laying hens. In both experiments, hens were subjected to consecutive 3-wk periods consisting of 1) a preinjection period, 2) an injection period, and 3) a postinjection period. During the 3-wk injection period, hens were injected once daily with either 5, 50 or 500 micrograms/kg BW of cGH or physiological saline (vehicle) alone (control group). In both experiments, injection of cGH did not affect (P greater than .05) percentage of daily egg production per hen, Haugh units, or BW during the injection period compared with preinjection hens. In Experiment 1, but not Experiment 2, control hens had reduced shell thickness and feed consumption during the injection and postinjection periods when compared with the preinjection controls. These reductions were not observed in hens receiving injections of cGH (all doses).


Synthesis and indole coupling reactions of azetidine and oxetane sulfinate salts.
Azetidine and oxetane sulfinate salts are easily prepared from commercially available 3-iodoheterocycle precursors in a three-step sequence. They undergo smooth coupling reactions thereby providing an expedient route for the introduction of these four-membered heterocycles into indoles.