Mulberry ethanol extract attenuates hepatic steatosis and insulin resistance in high-fat diet-fed mice.
Nonalcoholic fatty liver disease is one of the most common complications of obesity. Mulberry is an important source of phytochemicals, such as anthocyanins, polyphenols and flavonoids, which are related to its antioxidant activity. In this study, we developed a hypothesis that mulberry exerted beneficial effects on metabolic disorders and evaluated the influence of the mulberry ethanol extract (MEE) on high-fat diet-induced hepatic steatosis and insulin resistance in mice. Thirty-six male C57BL/6J mice were assigned into 3 groups and fed either a low-fat diet or a high-fat diet with or without supplementation with MEE. Our results showed that administration of MEE reduced diet-induced body weight gain, improved high-fat diet-induced hepatic steatosis and adipose hypertrophy, alleviated insulin resistance, and improved glucose homeostasis. Analysis of hepatic gene expression indicated that MEE treatment changed the expression profile of genes involved in lipid and cholesterol metabolism. In conclusion, the present study demonstrated that MEE supplementation protected mice from high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Moreover, the protective effects of MEE were associated with the induction of fatty acid oxidation and decreased fatty acid and cholesterol biosynthesis.


An unusual presentation of gastric fistula following peptic perforation repair: A case report.
Peptic perforation repair is a common stomach surgery. This surgery has not been associated with delayed onset gastrocutaneous fistula formation. However such a complication has been reported following a variety of other stomach surgeries. We are reporting this case as it is a rare complication. Also its diagnosis and management is challenging. We are presenting a case of peptic perforation repair where burst abdomen happened in the immediate post-operative period. The patient was put on conservative management. He responded well to it but his abdominal wound was not healing. After a wait of four months the wound was covered with a skin graft. The graft uptake was satisfactory but a discharging ulcer appeared on it. This condition persisted for one month. Finally a computed tomography Fistulogram (CT Fistulogram) was performed. It revealed an underlying complex gastric fistula. A repeat surgery was performed. A gastrocutaneous fistula diagnosed at sixth month following the peptic perforation repair and causing minimal discomfort to the patient is a rare presentation. The abdominal wound following the surgery was possibly not healing because of the underlying fistula.


Adjuvant trastuzumab in elderly with HER-2 positive breast cancer: a systematic review of randomized controlled trials.
Trastuzumab, in combination with chemotherapy, is the gold standard in the adjuvant treatment of patients with HER2 positive breast cancer. Limited data are available on the role of adjuvant trastuzumab in the elderly population. We performed a systematic review of prospective randomized trials with available data on the use of adjuvant trastuzumab in patients older than 60years, focusing on both the efficacy and the cardiac safety. Data extrapolated from two prospective trials were included for efficacy and cardiac safety. A significant 47% relative risk reduction was observed in elderly patients receiving trastuzumab compared to chemotherapy alone (pooled Hazard Ratio: 0.53; 95% CI, 0.36-0.77). The pooled proportion of cardiac events in elderly patients treated with trastuzumab was 5% (95% CI, 4-7%). The use of trastuzumab should be considered as a standard of care in the adjuvant therapy of elderly patients with HER-2 positive breast cancer. Acute and chronic medical conditions, nutritional status and level of daily activities should be considered. Uncertainty about cardiac safety in the elderly is a major concern.


Bowel-associated dermatosis-arthritis syndrome after biliopancreatic diversion.
The bowel-associated dermatosis-arthritis syndrome (BADAS), originally called the bowel bypass syndrome, and described after jejuno-ileal bypass, has subsequently been reported in association with inflammatory bowel disease and after gastric resection. BADAS has not been reported after biliopancreatic diversion (BPD). This case report describes a 47-year-old female who presented with recurrent skin rashes and arthralgia after a BPD, consistent with a clinical diagnosis of BADAS which was confirmed by skin biopsy. To date, she has been managed with cyclical courses of antibiotics without reversal of her surgery. This syndrome may be under-diagnosed and is a condition with which bariatric surgeons should be familiar.


The impacts of global atmospheric circulations on the water supply in select watersheds in the Indonesian Maritime Continent using SPI.
Despite the diverse atmospheric circulations affecting the Indonesian Maritime Continent (IMC), i.e., El Nino Southern Oscillation-ENSO, Indian Ocean Dipole-IOD, Madden Julian Oscillation-MJO, Monsoon, there is a lack of research on their interaction with hydrological events in watersheds. This study fills this gap by providing insights into the dominant atmospheric events and their correlation with the water supply in three characteristic watersheds, i.e., Tondano (north/Pacific Ocean), Jangka (south/Indian Ocean), and Kapuas (equatorial/interior) in IMC. The research used the standardized precipitation index for the 1-monthly (SPI1), 3-monthly (SPI3), and 6-monthly (SPI3) scale generated from 23 years (2000-2022) of monthly historical satellite rainfall data. The analysis compared each location's SPI indices with the monthly Nino 3.4, Dipole Mode Index (DMI), MJO (100E and 120E), Monsoon index, and streamflow data. The result shows that the dominant atmospheric events for the Tondano watershed were ENSO, IOD, and MJO, with correlation values of -0.62, -0.26, and -0.35, respectively. The MJO event was dominant for the Kapuas watershed, with a correlation value of -0.28. ENSO and IOD were dominant for the Jangka watershed, with correlation values of -0.27 and -0.28, respectively. The monsoon correlated less with the SPI3 in all locations, while it modulates the wet and dry period pattern annually. Most intense dry periods in Tondano occur with the activation of El Nino, while the intense wet period occurs even in normal atmospheric conditions. Most intense wet periods in Jangka occur with the activation of La Nina, while the intense dry period occurs even in normal atmospheric conditions. The occurrence of MJO compensates for the intense wet and dry periods in Kapuas. The correlation among SPI3, atmospheric circulation, and streamflow in the diverse watershed characteristics in the IMC watersheds could give strategic information for watershed management and applies to other watersheds with similar atmospheric circulation characteristics.


miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2.
Aerobic glycolysis was closely associated with the malignant transformation and prognosis of tumours. miR-206 was found to be downregulated in several cancers. However, whether miR-206 functions in non-small-cell lung cancers (NSCLCs) via the process of aerobic glycolysis remains poorly characterized. Quantitative real-time PCR was performed to detect miR-206 level in NSCLC cells and tissues. The effect of miR-206 on hexokinase 2 (HK2) expression was examined through miR-206 overexpression or miR-206 knockdown. CCK-8 assay and colony formation assay were carried out to explore the role of miR-206 on cell proliferation and colony formation, respectively. The relationship between miR-206 and HK2 was measured by dual-luciferase reporter assay. Glucose consumption, lactate production assay and ATP generation were performed in NSCLC cells following miR-206 and HK2 overexpression. We found that miR-206 was downregulated in NSCLC tissues and cells. miR-206 overexpression downregulated the expression of HK2 via targeting HK2 3'UTR in NSCLC cells. In addition, miR-206 decreased the cell viability and colony formation in NSCLC cells. Furthermore, miR-206 reduced glucose uptake, lactate production and ATP generation in NSCLC cells via HK2 repression. In conclusion, these findings suggested that miR-206 regulated NSCLC cell aerobic glycolysis by targeting HK2.


Gastric acid response to modified sham feeding in patients with duodenal ulcer: is increased vagal tone the cause of basal acid hypersecretion?
In order to test the hypothesis that increased basal vagal tone causes basal acid hypersecretion in duodenal ulcer (DU), the effect of sham feeding on gastric acid secretion was studied in 26 patients with DU and 20 healthy controls. Basal acid output (BAO), sham feeding-stimulated acid output (SAO) and peak histamine-stimulated acid output (PAO) were significantly higher in DU patients compared with healthy controls (P less than 0.01). The BAO/PAO ratio in DU patients (0.28 +/- 0.03) was not significantly different from that of healthy subjects (0.19 +/- 0.03), indicating that the higher BAO in DU patients group, as a whole, was due to a higher parietal cell mass. The basal subtracted response to sham feeding expressed as a fraction of secretory capacity [(SAO-BAO)/PAO], which correlates inversely with the basal vagal tone, was not significantly different in the patients and control subjects (0.27 +/- 0.03 versus 0.3 +/- 0.03; P greater than 0.05). Based on the data from the healthy controls, a ratio of BAO/PAO greater than 0.44 was defined as abnormal (using 95% confidence limits) and it indicated marked basal acid hypersecretion. Four of 26 DU patients had basal acid hypersecretion (that is, BAO/PAO greater than 0.44), but only two of them did not show an increase over their basal rate of secretion in response to sham feeding. All other DU patients, including two with marked basal acid hypersecretion, and all healthy controls showed an appreciable increase in their acid secretion in response to sham feeding.(ABSTRACT TRUNCATED AT 250 WORDS)


Low-cost zeolitic carriers for delivery of hydroxychloroquine immunomodulatory agent with antiviral activity.
The coronavirus pandemic prompted scientists to look for active pharmaceutical ingredients that could be effective in treating COVID-19. One of them was hydroxychloroquine, an antimalarial and immunomodulatory agent exhibiting antiviral activity. The anchoring of this drug on porous carriers enables control of its delivery to a specific place in the body, and thus increases bioavailability. In this work, we developed low-cost zeolitic platforms for hydroxychloroquine. The waste solution generated during zeolite production from fly ashes was used in the synthesis of Na-A and Na-X carriers at laboratory and technical scale. The materials were characterized by high purity and single mineral phase composition. The surface charge of zeolites varied from negative at pH 5.8, and 7.2, to positive at pH 1.2. All samples indicated good sorption ability towards hydroxychloroquine. The mechanism of drug adsorption was based on electrostatic interactions and followed the Freundlich model. Zeolitic carriers modified the hydroxychloroquine release profiles at conditions mimicking the pH of body fluids. The mode of drug liberation was affected by particle size distributions, morphological forms, and chemical compositions of zeolites. The most hydroxychloroquine controlled release at pH 5.8 for the Na-X material was noted, which indicates that it can enhance the drug therapeutic efficacy.


Validation of a Nutritional Screening Tool for Ambulatory Use in Pediatrics.
To evaluate the use of Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) in a primary health care clinic in the community and to assess the impact of its use on medical staff's awareness of nutritional status. STAMP scoring system was tested as is and with modifications in the ambulatory setting. Nutritional risk according to STAMP was compared with a detailed nutritional assessment performed by a registered dietitian. Recording of nutrition-related data and anthropometric measurements in medical files were compared prior and post implementation. Sixty children were included (31 girls, 52%), ages between 1 and 6 years, mean age 2.8 ± 1.5 (mean ± SD). STAMP scores yielded a fair agreement between STAMP and the dietitian's nutritional assessment: κ = 0.47 (95% confidence interval [CI] 0.24-0.7), sensitivity of 47.62% (95% CI 28.34-67.63). Modified STAMP yielded more substantial agreement: κ = 0.57 (95% CI 0.35-0.79), sensitivity of 76.19% (95% CI 54.91-89.37), specificity of 82.05% (95% CI 67.33-91.02). The use of STAMP resulted in an increase in recording of appetite, dietary intake, and anthropometric measurements. Modification of the STAMP improved nutritional risk evaluation in community setting. The use of STAMP in a primary health care clinic raised clinician's awareness to nutritional status. Further work will identify whether this could be translated into lower malnutrition rates and better child care.


Consistent exposure to microplastics induces age-specific physiological and biochemical changes in a marine mysid.
In this study, a marine mysid, Neomysis awatschensis, was exposed to 1 × 103-5 × 105 particles mL-1 of polystyrene microbeads (1 and 10 μm). Exposure to microplastics (MPs) resulted in ingestion and egestion in feces. MPs exposure during the early stage resulted in mortality and oxidative stress, while more mature stages were increasingly tolerant to MPs. Feeding rates were inhibited by MPs, and age-specific oxidative stress was observed. Growth parameters were significantly affected by MPs with lower 20-hydroxyecdysone (20E) concentrations and longer intermolt durations. The number of hatched juveniles from females that were exposed to MPs was significantly lower than the control treatment, but no significant differences were observed between survival rates of newly hatched juveniles in the different treatments. Our results suggest that the detrimental effects of prolonged exposure to MPs could be age- and size-specific and harmful for the maintenance of mysid populations.


How-to conduct a systematic literature review: A quick guide for computer science research.
Performing a literature review is a critical first step in research to understanding the state-of-the-art and identifying gaps and challenges in the field. A systematic literature review is a method which sets out a series of steps to methodically organize the review. In this paper, we present a guide designed for researchers and in particular early-stage researchers in the computer-science field. The contribution of the article is the following:•Clearly defined strategies to follow for a systematic literature review in computer science research, and•Algorithmic method to tackle a systematic literature review.


Educational factors outweigh the importance of lifestyle factors for residency program applicants: an international comparative study.
Although studies have been conducted to identify factors that attract students to a career in surgery, the relative importance of factors that attract students to a particular training program remains unknown. Comparative data between countries may provide insights and ultimately provide guidance to program directors as they seek to attract the best applicants to their program. Blinded written survey, scored 1-5 on a list of 26 factors divided into 3 categories, including educational factors, lifestyle factors, and other. Jichi Medical University, Japan and the David Geffen School of Medicine at University of California-Los Angeles. Japan residents (N = 125), Japan Medical Students (N = 68), United States Residents (N = 99), and United States Students (N = 55). All 4 groups surveyed judged faculty quality among the most important factors, with educational program quality, clinical experience and perceptions of resident happiness also rated among the most important. A comparison of factors consistent with lifestyle and factors consistent with the educational program found significantly (p < 0.05) higher scores for educational factors by 3 groups surveyed. Resident applicants are most interested in training program factors related to the quality of the educational program and the faculty. Issues such as salary, vacation, night call, location, or benefits are considered less important. The results in Japan and the United States were remarkably similar despite major differences in the educational system and debt load at the time of graduation. Program directors should communicate the value of those factors considered important by applicants as part of the recruitment process.


Early morphological changes in cardiac mitochondria after subcutaneous administration of trastuzumab in rabbits: possible prevention with oral selenium supplementation.
Trastuzumab-mediated cardiotoxicity poses a significant challenge in the treatment of human epidermal growth factor receptor 2-positive breast cancer. To understand the underlying mechanisms, we conducted experiments to determine ultrastructural changes of rabbit cardiac tissue under different experimental conditions, including differing doses of trastuzumab and supplementation with oral sodium selenite, an antioxidant. Histopathology revealed lymphocyte and macrophage infiltration in myocardium of rabbits receiving four doses of trastuzumab. Transmission electron microscopy showed substantial changes with trastuzumab, including edema with separation of myofibril bundles and rupture of sarcomeres. Within mitochondria, edema resulted in disorganization of the cristae. Some mitochondria exhibited eccentric projections of their membranes with disruption of both inner and outer membranes. These changes were seen to a lesser extent in rabbits who received oral sodium selenite prior to trastuzumab. Selenium is integral to functioning of mitochondrial glutathione peroxidases, important antioxidants that also maintain membrane integrity. If mitochondria are disrupted as part of trastuzumab cardiac toxicity, selenium supplementation might be an important therapeutic or preventive consideration. Larger studies to explore this hypothesis are warranted.


Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.
Thyroid cancer (TC) is one of the most common endocrine system cancers, and its incidence is elevating. There is an urgent need to develop a deeper understanding of TC pathogenesis and explore new therapeutic target for its treatment. This study aimed to investigate the effects of pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) on the progression of TC. Herein, 29 pairs of TC and adjacent tissues were used to assess the expression of PLEKHG4. A xenograft model of mouse was established by subcutaneously injected with TC cells. Lung metastasis model was established through left ventricular injection. The results revealed that PLEKHG4 was up-regulated in human TC tissues. PLEKHG4 level was correlated with clinicopathological parameters of TC patients. In vitro assays revealed that PLEKHG4 promoted TC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation. Knockdown of PLEKHG4 led to the opposite effects, and the loss of PLEKHG4 enhanced the apoptosis ability and inhibited the stemness properties of TC cells. These findings were further confirmed by the in vivo growth and lung metastasis of TC tumor. Mechanistically, PLEKHG4 promoted the activation of RhoGTPases RhoA, Cdc42, and Rac1. The inhibitors of these RhoGTPases reversed the PLEKHG4-induced malignant phenotypes. Additionally, ubiquitin-conjugating enzyme E2O (UBE2O), a large E2 ubiquitin-conjugating enzyme acted as an ubiquitin enzyme of PLEKHG4, facilitated its ubiquitination and degradation. In conclusion, PLEKHG4, regulated by UBE2O, promoted the thyroid cancer progression via activating the RhoGTPases pathway. UBE2O/PLEKHG4/RhoGTPases axis is expected to be a novel a therapeutic target for TC treatment.


The use of the larval development assay for predicting the in vivo efficacy of levamisole against Haemonchus contortus and Trichostrongylus colubriformis.
The larval development assay has been used for many years to measure the sensitivity of the free-living life stages of trichostrongylid nematodes to anthelmintics. The assay has applications in both drug discovery and the diagnosis of drug resistance. We revisited the usefulness of the larval development assay for diagnosis of resistance to levamisole using field-derived isolates of Haemonchus contortus and Trichostrongylus colubriformis showing varying levels of resistance to this drug in vivo. Each of the resistant isolates showed a plateau in their larval development assay dose-response at the highest drug concentrations tested, representing a highly-resistant fraction, amounting to between 6.9 and 55.1% of the populations. The remaining population fractions for the resistant isolates showed IC50 values from 1.4- to 17.8-fold higher than their corresponding susceptible isolate of the same species. We used a data set from the DrenchRite® test user manual to derive equations describing the relationship between the IC50 values for these low / moderate resistance components of each population and in vivo drug efficacy, and then used these equations to estimate the expected in vivo efficacy of levamisole against this population component of each isolate. A combination of this expected efficacy, with the known zero efficacy of the drug in vivo against the highly-resistant population fractions in each isolate, allowed us to calculate a predicted drug efficacy for the whole population for each isolate. The predicted levamisole efficacies for the three resistant H. contortus isolates were 88.8, 84.1 and 43.7%. These compared favourably with the actual efficacy of the drug against these isolates as determined in faecal egg count reduction tests or total worm count studies: 79, 66.3 and 40.6%, respectively. Similarly, for T. colubriformis, predicted efficacies of 82.0 and 1.8% compared favourably with the actual efficacies of 65-92 % and 0%, respectively. This study illustrates the usefulness of the larval development assay as a diagnostic tool for predicting in vivo efficacy of levamisole against H. contortus and T. colubriformis.


[Transcapillary fluid exchanges. A program in Basic].
Transcapillary fluid exchanges are analysed with the Wiederhielm's model programmed in this study in Basic language. The physiological variable which are taken in account are: arterial and venous capillary pressures, interstitial pressure and the colloid osmotic pressure of plasma and tissue proteins. This model shows the relationship between filtration, reabsorption, plasma leakage and the lymph flow. Edema resulting from venous and lymphatic obstruction or from a decrease in plasma oncotic pressure are simulated.


Quantification of angiotensin iontophoresis.
A method of value for studying the effects of angiotensin II (AII) and angiotensin III (AIII) on the brain is microiontophoresis combined with single unit recording. The purpose of this study was to quantitate the release of angiotensins under various experimental conditions thus providing a firm basis for the iontophoretic application of angiotensins. Quantification of release was accomplished by adding the appropriate [3H]angiotensin to 1 X 10(-3) M solutions of AII and AIII and then measuring the counts released from the tip of the microiontophoretic pipette in vitro into a small volume of Ringer solution. Although both AII and AIII were released by diffusion from micropipettes, this release could all but be eliminated with a retaining current of 20 nA. The release of AII and AIII was linear with respect to the amount of ejecting current applied up to 60 nA, the highest current examined. Angiotensin II at pH 4.5 and AIII at pH 3.5 were released at similar rates of 41.5 and 45.1 fmol/min/nA respectively. Raising the pH of the AII solution to 4.5 reduced the rate of release to 17.9 fmol/min/nA. Transport numbers were determined as follows: AII pH 3.5-0.115; AII pH 4.5-0.035, and AIII pH 4.5-0.145. It can be concluded that angiotensins are readily released by microiontophoresis, the response is linear with respect to application current, and that with the use of the appropriate pH the rate of release of AII and AIII are comparable.


The impact of fiscal austerity on suicide mortality: Evidence across the 'Eurozone periphery'.
While linkages between some macroeconomic phenomena and suicides in some countries have been explored, only two studies, hitherto, have established a causal relationship between fiscal austerity and suicide, albeit in a single country. The aim of this study is to provide the first systematic multiple-country evidence of a causal relationship of fiscal austerity on time-, gender-, and age-specific suicide mortality across five Eurozone peripheral countries, namely Greece, Ireland, Italy, Portugal and Spain over the period 1968-2012, while controlling for various socioeconomic differences. The impact of fiscal adjustments is found to be gender-, age- and time-specific. Specifically, fiscal austerity has short-, medium- and long-run suicide increasing effects on the male population in the 65-89 age group. A 1% reduction in government spending is associated with a 1.38%, 2.42% and 3.32% increase in the short-, medium- and long-run, respectively, of male suicides rates in the 65-89 age group in the Eurozone periphery. These results are highly robust to alternative measures of fiscal austerity. Improved labour market institutions help mitigate the negative effects of fiscal austerity on suicide mortality.


Primary care physician insights into a typology of the complex patient in primary care.
Primary care physicians play unique roles caring for complex patients, often acting as the hub for their care and coordinating care among specialists. To inform the clinical application of new models of care for complex patients, we sought to understand how these physicians conceptualize patient complexity and to develop a corresponding typology. We conducted qualitative in-depth interviews with internal medicine primary care physicians from 5 clinics associated with a university hospital and a community health hospital. We used systematic nonprobabilistic sampling to achieve an even distribution of sex, years in practice, and type of practice. The interviews were analyzed using a team-based participatory general inductive approach. The 15 physicians in this study endorsed a multidimensional concept of patient complexity. The physicians perceived patients to be complex if they had an exacerbating factor-a medical illness, mental illness, socioeconomic challenge, or behavior or trait (or some combination thereof)-that complicated care for chronic medical illnesses. This perspective of primary care physicians caring for complex patients can help refine models of complexity to design interventions or models of care that improve outcomes for these patients.


Chromosomal aberrations induced by maleic hydrazide and related compounds in Chinese hamster cells in vitro.
The cytotoxic effects and chromosomal abnormalities induced by maleic hydrazide (MH) and its salts were investigated in cultured V79 cells. MH, and its potassium (K-MH) and diethanolamine (DEA-MH) salts were tested. MH was 5--14 times more cytotoxic than its salts and almost 4.5 times less toxic than the related compound, hydrazine dihydrochloride (HDC). MH salts had very weak cytotoxicity; the LD50 values on V79 cells on exposure for 3 h in vitro were (in microgram/ml) 1100 (MH), 12 000 (DEA-MH), 20 000 (K-MH), 230 (HDC) and 10 000 (NaCl). Both MH and its salts--but neither HDC nor NaCl--caused chromosomal aberrations in cultured V79 cells. The maximal frequencies of aberrant cells in cultures exposed to the compounds for 3 h in vitro were 18% (mh at 100 microgram/ml), 18% (K-MH at 20 000 microgram/ml) and 13% (DEA-MH at 20 000 microgram/ml). Maximal frequencies observed in cultures treated with HDC or NaCl were 10% (HDC at 400 microgram/ml) and 5% NaCl at 10 000 microgram/ml). Those of positive groups were 97% (N-methyl-N'-nitro-N-nitrosoguanidine, MNNG, at 5 microgram/ml) and 16% (ethyl methanesulfonate, EMS, at 400 microgram/ml). These frequencies of MH and its salts were 3.25--4.5 times those in untreated control cells. These results suggested that MH and its salts had weak inducibili


Brainstem-vermis and brainstem-tentorium angles allow accurate categorization of fetal upward rotation of cerebellar vermis.
To evaluate the role of the brainstem-vermis (BV) and brainstem-tentorium (BT) angles in the differential diagnosis of upward rotation of the fetal cerebellar vermis. The BV and BT angles were measured retrospectively on median sonographic views of the brain in 31 fetuses at 19-28 weeks' gestation with upward rotation of the cerebellar vermis due to Blake's pouch cyst (n = 12), Dandy-Walker malformation (n = 12) and cerebellar vermian hypoplasia (n = 7). Eighty normal fetuses at 20-24 weeks were included as controls. In the control group, BV and BT angles were 9.1 ± 3.5° (range, 4-17°) and 29.3 ± 5.8° (range, 21-44°), respectively. The BV angle was significantly increased in each of the three subgroups of anomalies: Blake's pouch cyst (23 ± 2.8°; range, 19-26°), vermian hypoplasia (34.9 ± 5.4°; range, 24-40°) and Dandy-Walker malformation (63.5 ± 17.6°; range, 45-112°), the angle increasing with increasing severity of the condition. The BT angle had a similar pattern but there was overlap among the different groups. The BV angle and, to a lesser degree, the BT angle are simple and reproducible measurements that provide valuable additional information for the categorization of upward rotation of the fetal cerebellar vermis. From mid gestation, a BV angle > 45° is strongly suggestive of a Dandy-Walker malformation, while a measurement < 30° favors the diagnosis of a Blake's pouch cyst.


Stimulation by growth hormone of somatostatin release from the rat hypothalamus in vitro.
Growth hormone (GH) has been shown to cause a dose-dependent increase in the release of immunoreactive somatostatin from the rat hypothalamus in vitro, thus providing further evidence that GH may be involved in a "short loop" feedback, controlling its own secretion via hypothalamic somatostatin release.


[The Goblets test: Norms in the elderly population and properties in the detection of cognitive impairment in elderly individuals selected from the general population].
Most current tools exploring visuospatial memory abilities are poorly adapted to the elderly population. The Goblets test allows a brief evaluation of visuospatial memory abilities through an encoding phase in which the participant has to learn a particular sequence and a further delayed recall phase. The aim of the present work was to produce normative scores for this test and to study its properties in the detection of dementia. Data were collected in a sample of 1002 agricultural retirees aged 65 years and over included in the AMI study, a population-based cohort study conducted in Gironde (southwestern France). The sample analyzed to establish normative data included 795 non-institutionalized and non-demented participants. Regarding the validity study, the sample analyzed included 912 participants of whom 76 subjects with a diagnosis of Alzheimer's disease. Normative scores were calculated according to age (65-74 years and 75 years and over) and educational level (primary school level not validated by a diploma, primary school level validated by a diploma and more than a primary school level). The normative scores of the learning phase were described using the percentiles while rates of success were reported for the delayed recall. Regarding the properties of the test, the Goblets test seemed to be more specific than sensitive and presented high negative predictive values. The Youden index showed that the better cut-off score was two trials (with 75.0% sensitivity and 83.0% specificity). The Goblets test can be a helpful tool in screening for dementia. Nevertheless, like many other simple and quick cognitive tests, it cannot be used alone to establish the diagnosis of dementia. This test has the advantage to be easy to administer in clinical situations; the normative scores presented in this study could be used as an aid to interpret a patient's performance.


10-omega-phenylalkyl-9(10H)-anthracenones as inhibitors of keratinocyte growth with reduced membrane damaging properties.
Work aimed at further improving the benefit to risk ratio of the antipsoriatic agent anthralin has led to 10-omega-phenylalkyl-9(10H)-anthracenones, members of which are equally potent as inhibitors of the growth of HaCaT keratinocytes. In contrast to anthralin, induction of membrane injury is strongly reduced as documented by the release of LDH activity from cytoplasm of keratinocytes.


Myopathic mutations in the β-chain of tropomyosin differently affect the structural and functional properties of ββ- and αβ-dimers.
Tropomyosin (Tpm) is an actin-binding protein that plays a vital role in the regulation of muscle contraction. Fast skeletal muscles express 2 Tpm isoforms, α (Tpm 1.1) and β (Tpm 2.2), resulting in the existence of 2 forms of dimeric Tpm molecule: αα-homodimer and αβ-heterodimer. ββ-Homodimer is unstable and absent in the native state, despite which most of the studies of myopathy-relating Tpm mutations have been performed on the ββ-homodimer. Here, we applied different methods to investigate the effects of myopathic mutations R133W and N202K in the β-chain of Tpm on properties of αβ-heterodimers and to compare them with the features of ββ-homodimers with the same mutations. The results show that properties of αβ-Tpm and ββ-Tpm with substitutions in the β-chain differ significantly, and this indicates that the effects of myopathic mutations in the Tpm β-chain should be studied on the Tpm αβ-heterodimer.-Bershitsky, S. Y., Logvinova, D. S., Shchepkin, D. V., Kopylova, G. V., Matyushenko, A. M. Myopathic mutations in the β-chain of tropomyosin differently affect the structural and functional properties of ββ- and αβ-dimers.


Biosynthesis of a low molecular weight collagen by rabbit growth plate cartilage organ cultures.
Analysis of [14C]-proline labeled proteins synthesized by organ cultures of rabbit growth plate cartilage slices revealed that this tissue synthesized a low molecular weight collagen in addition to Type II, 1 alpha, 2 alpha, and 3 alpha collagens. This collagen appears to be a distinct molecular species on the basis of electrophoretic mobility, hydroxyproline content and cyanogen bromide peptide mapping. In subsequent studies, a non-disulfide-bonded, higher molecular weight form of the same molecule was identified.


1-(4,4''-Difluoro-5'-meth-oxy-1,1':3',1''-terphenyl-4'-yl)ethanone.
In the title compound, C(21)H(16)F(2)O(2), the central benzene ring is inclined at dihedral angles of 30.91 (8) and 46.88 (7)° to the two terminal fluoro-substituted rings. The dihedral angle between the two terminal fluoro-subsituted rings is 68.34 (8)°. An intra-molecular C-H⋯O hydrogen bond generates an S(6) ring motif. The crystal structure is stabilized by weak C-H⋯π inter-actions.


Beyond the Bud: Emerging Methods of Cannabis Consumption for Youth.
Cannabis continues to be the most widely used illicit substance among youth, as many teens view the risks of cannabis consumption to be low. With cannabis laws becoming lax and dispensaries becoming more prevalent throughout the United States, highly concentrated Δ-9-tetrahydrocannibinol (THC) is becoming readily available. This article examines the available literature on consumption of concentrated THC, focusing on potential consequences of concentrate use among youth. Various methods for consuming concentrated THC, including ingestion of edibles, vaping, and dabbing, are discussed, along with associated risks of each consumption method. Recommendations for health professionals are provided.


Identifying children who are susceptible to dropping out from physical activity and sport: a cross-sectional study.
Although the benefits of physical activity are clear, adherence to physical activity programs is a challenge, especially during transitional phases of life. We aimed to identify adolescents who were more likely to drop out from physical activity and sports participation, from childhood to adolescence. This was a cross-sectional study on retrospective data regarding childhood activity among 803 Brazilian adolescents. The study was conducted at public schools in Londrina, Paraná, in 2011. Habitual physical activity, sports participation during childhood, parental physical activity, socioeconomic status and perception of social relationships were self-reported. Cardiorespiratory fitness was estimated via a 20-m shuttle-run test and somatic maturation was estimated from the age at peak height velocity. Our results provided evidence that girls (physical activity: odds ratio, OR: 4.37 [95% confidence interval, CI: 1.86-10.3]; sports: OR: 2.65 [95% CI: 1.39-5.05]) and adolescents with low cardiorespiratory fitness (physical activity: OR: 1.77 [95% CI: 1.13-2.78]; sports: OR: 1.62 [95% CI: 1.15-2.26]) were more likely to drop out from active behaviors. Children with inactive mothers and inactive fathers (OR: 3.55 [95% CI: 1.12-11.3]) also showed a higher dropout rate from physical activity. Adolescents with negative perceptions of friendships (OR: 2.33 [95% CI: 1.21-4.47]) were more likely to drop out from sports. Higher dropout rates from active lifestyles during childhood were observed among girls and adolescents with low cardiorespiratory fitness. Parental inactivity and negative perceptions of friendships were also potential risk factors for discontinuation of childhood physical activity and sports.


Postnatal redistribution of pericruciate motor cortical projections within the kitten spinal cord.
The anatomical distribution of pericruciate cortical axons in the spinal cord was examined using anterograde transport of WGA-HRP from multiple unilateral injections into defined regions of the pericruciate cortex (PC) in 20 time-mated kittens and 3 adult cats. The gray matter and descending white matter tract distributions of WGA-HRP-labelled densities were analyzed using computerized morphometry and 3-dimensional reconstruction. In kittens older than 16 days postnatal (dPN), PC axon densities were found in dorsolateral column tracts corresponding to those of the adult, indicating that the white matter projections from the PC were largely established by this age. However, in kittens less than 38-44 dPN (about 105-109 days gestation), the spinal gray matter PC axon densities were distributed widely (so as to involve dorsal, intermediate and ventral laminae, e.g., I to IX) and bilaterally at all levels of the spinal cord. This contrasted sharply with the adult spinal cord in which the majority of densities was localized to laminae IV-VII on the contralateral side. The proportion of PC densities counted in the ipsilateral grey matter of neonates was found to average 23% of the total gray matter projection, while in adults this value was 9%. In all animals, by about 44 dPN, the terminal fields became effectively restricted to the adult distribution, that is, focused predominantly in the medial portions of laminae IV-VII in the gray matter contralateral to the cortical injection site.


Role of non-governmental organizations in poverty reduction in the global South: evidence from world vision Ghana, Kintampo South district.
Poverty is a global issue, particularly in the Global South. This has made its reduction vital, although official efforts have yielded modest results. As a result, non-state entities such as non-governmental organizations (NGOs) arose to supplement the government's poverty reduction initiatives. Even though there have been studies on the role of NGOs in poverty reduction in the Global South, the results remain inconclusive. As such, this study investigates World Vision Ghana's (WVG) impact on poverty reduction. The study employed an after-only design. The sample size was 384 people, and the data were collected utilizing questionnaires and an interview guide. Descriptive statistics, parametric and non-parametric analysis, and thematic analysis were used to analyze the data. It was discovered that WVG used both demand-side and supply side approaches to poverty reduction, which helped increase earnings, acceptable food consumption, access to potable water and toilet facilities, human capital development, and understanding of children's rights. However, WVG's operation is hampered by low literacy among clients, an uncertain rainfall pattern, insufficient funding, and loan non-payment. WVG's interventions largely contributed to poverty reduction. As a result, the promotion of demand and supply side approaches to poverty reduction, the establishment of literacy programs, and the sensitization of recipients on the need for loan repayment are critical in boosting the success of WVG's interventions and ensuring sustainability of outcomes.


DNA templated Click Chemistry via 5-vinyl-2'-deoxyuridine and an acridine-tetrazine conjugate induces DNA damage and apoptosis in cancer cells.
Click Chemistry is providing valuable tools to biomedical research, but its direct use in therapies remains nearly unexplored. For cancer treatment, nucleoside analogues (NA) such as 5-vinyl-2'-deoxyuridine (VdU) can be metabolically incorporated into cancer cell DNA and subsequently "clicked" to form a toxic product. The inverse electron-demand Diels-Alder (IEDDA) reaction between VdU and an acridine-tetrazine conjugate (PINK) has previously been used to label cell nuclei of cultured cells. Here, we report tandem usage of VdU and PINK to induce cytotoxicity. Cell lines were subsequently treated with VdU and PINK, and cell viability was measured via well confluency and 3D tumor spheroid assays. DNA damage and apoptosis were evaluated using Western Blotting and cell cycle analysis by flow cytometry. Double stranded DNA break (DSB) formation was measured using the comet assay. Apoptosis was assessed by fluorescent detection of externalized phosphatidylserine residues. We report that the combination of VdU and PINK synergistically induces cytotoxicity in cultured human cells. The combination of VdU and PINK strongly reduced cell viability in 2D and 3D cultured cancer cells. Mechanistically, the compounds induced DNA damage through DSB formation, which leads to S-phase accumulation and apoptosis. The combination of VdU and PINK represents a novel and promising DNA-templated "click" approach for cancer treatment via selective induction of DNA damage.


Relaxation therapies in the treatment of psoriasis and possible pathophysiologic mechanisms.
Psychologic factors play a role in many dermatologic disorders, giving rise to the possible use of psychotherapeutic modalities in treatment. Regarding psoriasis, emotional factors have a strong correlation with onset and flare-ups. The psychophysiologic mechanisms involved are not known; however, stress and its effect on the autonomic nervous system and the immune system may play a significant role in the onset and course of psoriasis. Relaxation and mere suggestion also affect the autonomic nervous system and the immune system and therefore may affect the course of the skin disorder. A few case studies have documented successful treatment of psoriasis with hypnosis and biofeedback. Further study of this process is needed, and the role of stress in dermatologic diseases must always be given consideration.


Stability and quantum yield effects of small molecule additives on solutions of semiconductor nanoparticles.
The effect of additives on the photostability of semiconductor nanoparticles was studied using CdSe, CdSe/ZnSe and CdSe/ZnS particles of various sizes and composition. The additives included phosphine oxides, amines, and antioxidants. Strong initial enhancement of band edge emission by hexadecylamine was observed for the uncoated particles but stability over a week period in light and air was shown to be poor. Inorganic coatings rendered the nanoparticles initially insensitive to additive but provided little extra stability in terms of photoluminescence. Antioxidant was shown to be effective at reducing the rate of photooxidative degradation for all particles in chloroform but not in toluene.


Reduced frontostriatal functional connectivity and associations with severity of Internet gaming disorder.
Cognitive, functional, and structural brain factors involving frontal executive and striatal reward networks have been implicated in Internet gaming disorder (IGD). However, frontostriatal network connectivity and its association with addiction severity are poorly understood in IGD. Resting-state fMRI data from 337 subjects (130 with IGD, 207 with recreational game use [RGU]) were collected. Striatal-cortical communications were measured with resting-state functional connectivity (FC) using coherent spontaneous fluctuations in the blood-oxygenation-level-dependent fMRI signal. Correlations were calculated between FC measures and IGD-related assessments (addiction severity and craving scores). Decreased FC was predominantly observed in IGD subjects, with IGD subjects showing decreased FC between the putamen and superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and the ventral striatum and IFG, superior temporal gyrus, and MFG. Disorder severity and craving scores were negatively correlated with FC between striatal and frontal brain regions. Associations between diminished FC in corticostriatal circuitry and clinical features (IGD craving, severity) suggest potential therapeutic targets for neuromodulation treatments. The extent to which frontostriatal circuits involving executive control over reward processes may be altered to treat IGD warrants additional study.


Differential placental methylation and expression of VEGF, FLT-1 and KDR genes in human term and preterm preeclampsia.
Preeclampsia, a pregnancy complication of placental origin is associated with altered expression of angiogenic factors and their receptors. Recently, there is considerable interest in understanding the role of adverse intrauterine conditions in placental dysfunction and adverse pregnancy outcomes. Since we have observed changes in placental global DNA methylation levels in preeclampsia, this study was undertaken to examine gene promoter CpG methylation and expression of several angiogenic genes.We recruited 139 women comprising, 46 normotensive women with term delivery (≥37 weeks), 45 women with preeclampsia delivering preterm (<37 weeks) and 48 women with preeclampsia delivering at term. Expression levels and promoter CpG methylation of VEGF, FLT-1 and KDR genes in placentae from respective groups were determined by Taqman-based quantitative real time PCR and by the Sequenom® EpiTYPER™ technology respectively. We observed several differentially methylated CpG sites in the promoter regions of VEGF, FLT-1 and KDR between the normotensive and preeclampsia groups. We specifically observed hypomethylated CpGs in the promoter region and an increased expression of VEGF gene between term and preterm preeclampsia. However, mean promoter CpG methylation could not account for the higher expression of FLT-1 and KDR in preterm preeclampsia as compared to normotensive group. Our data indicates altered DNA methylation patterns in the VEGF, FLT-1 and KDR genes in preeclampsia as compared to the normotensive group, which could be involved in the pathophysiology of preeclampsia. Hypomethylation of VEGF promoter and consequent upregulation of VEGF mRNA levels could be a compensatory mechanism to restore normal angiogenesis and blood flow in preterm preeclampsia. This study suggests a role of altered DNA methylation in placental angiogenesis and in determining adverse pregnancy outcomes.


Elevated testicular temperature modulates expression patterns of sperm proteins in Holstein bulls.
The objective of this study was to determine the effects of elevated testicular temperature on the expression patterns of sperm proteins in bulls. Ejaculates were collected from sexually mature Holstein bulls (n = 6) twice weekly for 10 weeks. Testicular temperature was elevated in all bulls by scrotal insulation for 72 consecutive hours during Week 2. Triton X-100 extracts of sperm proteins were prepared and subjected to SDS-PAGE. Sperm proteins in the 110 kDa range decreased from pre-thermal insult to Day 28 (start of thermal insult = Day 0), concurrent with decreases in sperm concentration, motility, and morphology, and subsequently increased, approaching pre-thermal insult values by Day 40. Based on mass spectrometry, this band was comprised of angiotensin converting enzyme (ACE), Hexokinase-1, and the alpha-4 subunit of Na(+)/K(+)ATPase. Changes in the expression patterns of these proteins were confirmed by immunoblotting, including the use of a custom antibody against the alpha-4 subunit of Na(+)/K(+)ATPase (testis-specific isoform). Furthermore, a 25 kDa sperm protein (identified as tissue inhibitor of metalloproteinase-2; TIMP-2), had a low expression level in pre-thermal insult samples, increased to Day 28 of post-thermal insult, and subsequently decreased to the pre-thermal insult level by the end of the experimental period. In conclusion, we identified proteins that may serve as molecular markers of impaired sperm function due to elevated testicular temperature, with important implications for fertility predictions. To our knowledge, this is the first report of the identification of a testis-specific isoform of Na(+)/K(+)ATPase in bovine sperm.


Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls.
This study evaluated the serum level of MKRN3 and investigated its diagnostic usefulness in girls with central precocious puberty (CPP). In total, 41 girls with CPP and 35 age-matched normal control girls were enrolled. Serum values of MKRN3 were measured in both groups. Gonadotropin and estradiol concentrations were evaluated after 6 and 12 months of GnRH agonist (GnRHa) treatment in CPP patients. The MKRN3 concentrations were much lower in the patient group than in the control group (p = .005). Over 1 year of GnRHa treatment in patients, the gonadotropin concentrations were significantly decreased (p < .05), while the MKRN3 concentrations were unchanged (p > .05). MKRN3 levels were inversely correlated to standard deviation (SD) in height (r = -0.46, p = .000), SD in weight (r = -0.32, p = .005), Tanner stage (r = -0.41, p = .000), and bone age (r = -0.46, p = .000). Based on ROC analysis, the area under curve was 0.758 for MKRN3, with 82.9% sensitivity and 68.5% specificity. The measurement of serum MKRN3 level may provide some help for CPP prediction, but relatively various values need further validation.


Same same, but different: A psychometric examination of three frequently used experimental tasks for cognitive bias assessment in a sample of healthy young adults.
Cognitive bias research draws upon the notion that altered information processing is key for understanding psychological functioning and well-being. However, little attention has been paid to the question of whether the frequently used experimental paradigms hold adequate psychometric properties. The present study examined the psychometric properties of three widely used cognitive bias tasks: the Approach-Avoidance Task (AAT), the visual dot-probe-task, and the Implicit Association Test (IAT). Approach, attentional, and association biases towards valenced stimuli were repeatedly measured at five different time points in a sample of 79 healthy young adults. Two different devices were used for assessment: a personal computer (PC) and a touchscreen-based tablet. Reliability estimates included internal consistency and temporal stability. Validity was inferred from convergence across different behavioral tasks and correlations between bias scores and self-reported psychological traits. Reliability ranged widely amongst tasks, assessment devices, and measurement time points. While the dot-probe-task appeared to be completely unreliable, bias scores obtained from the PC-based version of the AAT and both (PC and touchscreen) versions of the IAT showed moderate reliability. Almost no associations were found across information processing tasks or between implicit and explicit measures. Cognitive bias research should adopt a standard practice to routinely estimate and report psychometric properties of experimental paradigms, investigate feasible ways to develop more reliable tools, and use tasks that are suitable to answer the precise research question asked.


Target temperature in post-arrest comatous patients. Is something changed in the postpandemic era?
The recommended target temperature in the treatment of comatous patients after cardiac arrest has recently changed. We analyzed the impact on the neurological outcome of a change in the target temperature from July 2021. This was a retrospective analysis comparing the discharge status of 78 patients with a target temperature of 33 °C (group 1) with that of 24 patients with a target temperature of 36.5 °C (group 2). Pearson chi-square and Mann-Whitney U tests were used. The initial rhythm was defibrillable in 65% of group 1 and 71% of group 2, and cardiac arrest was witnessed in 93% of group 1 and 96% of group 2. There was an adverse outcome (death or vegetative state) in 37 patients in group 1 (47%) compared to 18 in group 2 (74%) (Pearson chi-square 5.612, p = 0.018). In our series of patients, the temperature control target temperature change from 33 °C to 36.5 °C was associated with worse neurological outcome. Further studies are needed to evaluate the outcome of a generalized modification of temperature control targets in comatose patients after cardiac arrest in our postpandemic era.


Detection of N-glycans on small amounts of glycoproteins in tissue samples and sodium dodecyl sulfate-polyacrylamide gels.
N-linked glycans harbored on glycoproteins profoundly affect the character of proteins by altering their structure or capacity to bind to other molecules. Specific knowledge of the role of N-glycans in these changes is limited due to difficulties in identifying precise carbohydrate structures on a given glycoprotein, which arises from the large amounts of glycoprotein required for N-glycan structural determination. Here, we refined a simple method to purify and detect trace amounts of N-glycans. During the N-glycan purification step, most contaminants were removed by two kinds of columns: a graphite carbon column and a cellulose column. N-Glycans were identified with a three-dimensional high-performance liquid chromatography (HPLC) system. Using our method, a global analysis of N-glycans from human muscle biopsy samples and mouse brain sections was possible. By combining sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with our method, we refined analytical procedures for N-glycans from SDS-PAGE gels using hydrazinolysis to achieve a high N-glycan recovery rate. N-Glycans on as little as 1 μg of the target protein transferrin or immunoglobulin G (IgG) were easily detected. These methods allowed us to efficiently determine glycoprotein N-glycans at picomole (pmol) levels.


Release of [3H]serotonin and its binding protein from enteric neurons.
The release of [3H]5-HT and its binding protein, SBP, from the guinea pig enteric nervous system was analyzed. Release of both [3H]5-HT and [3H]NE from strips of longitudinal muscle with adherent myenteric plexus preloaded with the respective radioactive amine was evoked by high K+ and the ionophore X537A. However, Ca2+-dependence could not be shown for [3H]5-HT release by either agent or for [3H]NE release by X537A. However, Ca2+-dependence (as well as inhibition of release by high Mg2+ and tetrodotoxin) could be demonstrated for the release of radioactivity evoked by electrical field stimulation of everted segments of ileum preloaded by perfusion through the serosal lumen with [3H]5-HT. Light and electron microscopic radioautography revealed that the sources of released radioactivity were axons, especially axonal varicosities containing a mixture of small clear and large dense-cored vesicles. SPB, but not the cytosol marker protein, lactic dehydrogenase, was spontaneously released from the perfused everted ileum. A marked increase in SBP (but not LDH) release was provoked by electrical field stimulation at 10 Hz, and this increased release (but not the spontaneous release) was Ca2+-dependent. It is concluded that SBP and 5-HT are probably stored together, at least in part in vesicles, and that both can be released by exocytosis from depolarized axon terminals.


Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease.
We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Compared with patients receiving statin medication, patients without statins did not have increased cardiac mortality (even when low-density lipoprotein [LDL] levels were >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for fatal coronary events, independent of LDL levels. In conclusion, only elevated hs-CRP was selected as an independent predictor of death. Statin therapy is associated with elevated hs-CRP, with a risk reduction for fatal coronary events, independent of LDL levels; this, in part, may be explained by the anti-inflammatory effects on atherosclerosis.


Low-dose chemoradiotherapy followed by partial or radical cystectomy against muscle-invasive bladder cancer: an intent-to-treat survival analysis.
To evaluate the clinical outcomes of patients with muscle-invasive bladder cancer treated with a prospective institutional protocol composed of induction low-dose chemoradiotherapy (LCRT) plus partial or radical cystectomy. From March 1997 to March 2006, 102 patients with Stage T2-T4aN0M0 bladder urothelial carcinoma consecutively underwent transurethral resection of the bladder tumor followed by LCRT consisting of radiotherapy to the bladder (radiation dose 40 Gy) concurrent with two cycles of intravenous (20 mg/d for 5 days) or intra-arterial (100 mg) cisplatin. Depending to their post-LCRT tumor status, patients were recommended to undergo partial or radical cystectomy with curative intent. LCRT-related toxicity of grade 3 or greater was rare (3%). Of 97 eligible patients, 41 (42%) had a complete response, 29 (30%) a partial response, 24 (25%) had stable disease, and 3 (4%) progressive disease. Of the 97 patients, 19, underwent partial cystectomy, and 58 underwent radical cystectomy, 2 underwent transurethral resection of the bladder tumor, and 18 did not undergo surgery. The 5-year overall survival and cancer-specific survival (CSS) rate was 66% and 74%, respectively. The median follow-up was 43 months (range 3-126). On multivariate analysis, the response to LCRT had the strongest effect on CSS, and CSS was clearly stratified by the response to LCRT (P < .0001), with a 5-year CSS rate of 100% for the 41 patients with a complete response. The results of our study have shown that LCRT is an effective and less-toxic induction therapy against muscle-invasive bladder cancer. Our therapeutic protocol with LCRT plus partial or radical cystectomy yielded favorable survival outcomes. The response to LCRT was the strongest prognostic factor for CSS.


Prevalence and safety of diazoxide in the neonatal intensive care unit.
Diazoxide is used to treat infants with persistent hypoglycemia, but the prevalence of its use and adverse effects are not well described. We report demographic and clinical characteristics of infants treated with diazoxide in neonatal intensive care units (NICUs). Retrospective cohort study of infants 24-41 weeks' gestation admitted to 392 NICUs from 1997-2016, comparing characteristics between hypoglycemic infants exposed/not exposed to diazoxide. For diazoxide courses > 1 day, we report percentages of infants starting diuretics and/or developing new ventilator/oxygen requirement during therapy. Among 1,249,466 infants, 185,832 had hypoglycemia; 1066/185,832 (0.57%) received diazoxide. Diazoxide use increased over time (P = 0.001). Infants receiving diazoxide varied from 0-14.9% among centers. New diuretic courses were associated with 91/664 (14%), and new oxygen or ventilator requirement during therapy was associated with 64/556 (12%) and 34/647 (5%), respectively. Diazoxide use in NICU settings has increased over time. Infants receiving diazoxide commonly received diuretics.


Predicting acute myocardial infarction (AMI) 30-days mortality: Using standardised mortality ratio (SMR) as the hospital performance measure.
A standardised mortality ratio (SMR) is the hospital observed mortality divided by its predicted mortality and has been used as an indicator to monitor hospital performance. This study developed a model that predicted 30-day mortality for acute myocardial infarction (AMI) and compared the SMR among 41 Malaysian public hospitals using statistical process control charts. Data from referral centres and specialist hospitals with cardiology services were analysed. Both referral centres and specialist hospitals had comparable mortality, except for Hospitals A and B, which the study considered outliers. Two-thirds of the remaining hospitals had an SMR of above one (SMR 1.05-1.51), but the indices were still within the expected variations. The SMR coupled with a funnel plot and variable life adjusted display (VLAD) can identify hospitals with potentially higher than expected mortality rates.


The clinical utility of the pain assessment tool in ventilated, sedated, and muscle-relaxed neonates.
The neonatal Pain Assessment Tool (PAT) is considered a reliable and valid tool for assessing neonatal pain. No research has been conducted on the clinical utility of the PAT when assessing pain in ventilated, sedated, and muscle-relaxed neonates. The objective of the study was to determine the clinical utility of the PAT when assessing pain in ventilated, sedated, and muscle-relaxed neonates. Neonatal nurses from the Royal Children's Hospital completed online surveys to assess the clinical utility of the PAT. Three focus groups were then conducted to further explore the variation of pain scores from the survey and clarify the challenges in interpreting the pain score. Nurses perceived the PAT clinically useful in neonates who were ventilated and minimally sedated. However, the PAT was not clinically useful in neonates who were ventilated and heavily sedated or muscle-relaxed. Further exploration via focus groups highlighted two themes related to the 'variation in the timing of the pain score' and the 'integration of critical thinking and judgement' used when assessing pain in neonates. The clinical utility of the PAT is acceptable for minimally sedated neonates; however, it decreases the more sedated a neonate becomes, and the PAT's usefulness is extremely poor in the muscle-relaxed neonate. A better understanding of the timing and interpretation of the pain score in relation to the neonate's clinical status may enable improved decision-making and pain management. The PAT requires further validity, reliability, and clinical utility research, particularly in critically ill and muscle-relaxed neonates.


Isolation and analysis of partial cDNA sequence coding for superoxide dismutase in Wuchereria bancrofti.
Molecular characterization of Wuchereria bancrofti is essential to develop suitable anti-filarial drugs and vaccines. We describe here isolation, sequence analysis and cloning of a partial cDNA of an enzyme superoxide dismutase from this parasite. The immunoscreening of a lambda zap W. bancrofti microfilarial (Mf) cDNA library with microfilaremic sera had resulted in the isolation of several seroreactive clones including, WbSOD. This clone contained a 309 bp insert and showed significant nucleotide and deduced amino acid sequence homologies to the superoxide dismutases of other nematode parasites. The antioxidant property of this enzyme may have important contribution in the defense mechanism of the parasite against host immune response.


A model for the structure and functions of iron-responsive elements.
Most eukaryotic cells express two proteins, whose biosynthetic rates are determined by the intracellular iron status. The genes for both these proteins, ferritin and the transferrin receptor (TfR), are regulated at the post-transcriptional level, but by entirely different mechanisms. Ferritin mRNA levels are not affected by acute changes in iron availability. Ferritin biosynthesis is regulated translationally via a defined element contained within the 5' untranslated region (UTR) of the ferritin mRNA. This element has been highly conserved during evolution and has been termed an iron-responsive element (IRE). In contrast to ferritin, the regulation of TfR biosynthesis is mirrored by equivalent changes in TfR mRNA levels. The genetic information for this regulation is mostly located in the region of the gene encoding the 3' UTR of the TfR mRNA. Five elements that closely resemble the ferritin IRE are contained within the region which is critical for TfR regulation. The IRE is suggested to function by forming a specific stem-loop structure that interacts with a transacting factor in an iron-dependent fashion. We present a model that accommodates the mediation of distinct post-transcriptional regulatory phenomena via IREs.


Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing.
Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. Our study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure. Adoptive transfer of EVs from genetically defined mouse models are used here to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs. wildtype EVs in wound healing. We identify several members of the Serpin family of serine protease inhibitors that are absent in db/db EVs, then we overexpress Serpin A1, F2 and G1 in EVs to evaluate their effect on wound healing in db/db mice. Serpins have an important role in regulating levels of elastase, plasmin and complement factors that coordinate immune cell signaling in full thickness wounds in a diabetic model. Here, we establish a novel therapeutic approach by engineering the payload of EVs based on proteomic analysis. Serpin-loaded EVs were used to rescue the Serpin deficiency identified by proteomics and promote wound healing in db/db mice, as well as evaluated how EVs affected extracellular matrix remodeling and the resolution of tissue injury. Therefore, we propose that the identification of EV payloads that are downregulated in diabetic wounds can be systematically analyzed for their functional activity and potential as a therapeutic, based on whether their re-expression in engineered EVs restores normal kinetics of tissue repair in chronic wounds.


Updated view of tars for psoriasis: what have we learned over the last decade?
Tars are one of the most effective, unknown, and oldest therapies for psoriasis. They include coal tar (CT) and biomass-derived products. These treatments, particularly the CT, have proven to be cost-effective with long remission times compared to other systemic or topical treatments. However, they have hardly evolved in recent years, as they are not well-embraced by clinicians or patients because of concerns regarding cosmesis and safety. This review summarizes current knowledge about the chemical characterization, mechanism of action, toxicity, and clinical studies supporting the use of tars for psoriasis over the last decade. Trends within these above aspects are reviewed, and avenues of research are identified. CT is rich in polycyclic aromatic hydrocarbons, whereas biomass-derived tars are rich in phenols. While the activation of the aryl hydrocarbon receptor is involved in the antipsoriatic effect of CT, the mechanism of action of biomass-derived products remains to be elucidated. No conclusive evidence exists about the risk of cancer in psoriasis patients under CT treatment. Large, randomized, double-blind, controlled clinical trials are necessary to promote the inclusion of tars as part of modern therapies for psoriasis.


Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients.
The excision repair cross-complementation group 1 (ERCC1) plays an essential role in DNA repair and has been linked to resistance to platinum-based anticancer drugs among advanced non-small cell lung cancer (NSCLC) patients. We systematically evaluate whether ERCC1 Asn118Asn and C8092A genetic variants are associated with treatment response of platinum chemotherapy. We preformed a meta-analysis using ten eligible cohort studies (including 11 datasets) with a total of 1,252 NSCLC patients to summarize the existing data on the association between the ERCC1 Asn118Asn and C8092A polymorphisms and response to platinum regiments. Odds ratio or hazard ratio with 95% confidence interval were calculated to estimate the correlation. We found that neither ERCC1 C8092A polymorphism nor Asn118Asn variant is associated with different response of platinum-based treatment among advanced NSCLC patients. Additionally, these two genetic variants are not related to treatment response in either Caucasian patients or Asian patients. Our meta-analysis indicates that the ERCC1 Asn118Asn and C8092A polymorphisms may not be good prognostic biomarkers for platinum-based chemotherapy in patients with stage III-IV NSCLC.


Analysis of integrated UWB MIMO and CR antenna system using transmission line model with functional verification.
This paper discusses the equivalent circuit model and functional verification of an integrated antenna system as its main focus. The integrated antenna system consists of two independent antenna systems, namely the Cognitive Radio antenna and the Ultra Wide Band Multiple Iinput Multiple Output antenna. This article is split into two parts: The first part discusses the equivalent circuit of an integrated antenna system by optimizing the RLC values. The developed lumped equivalent circuit model produces the NB resonant frequencies, which is the same as the S-parameter obtained through EM simulation. The second part of this paper aims to discuss the experimental verification of an integrated CR antenna system with Bayesian learning-based spectrum sensing algorithms using Universal Software Radio Peripheral devices. Real-time sensing and communication functionalities are visualized in the LABVIEW monitor. The integrated antenna system is fabricated and measured after the simulation.


Effects of drought stress on growth, solute accumulation and membrane stability of leafy vegetable, huckleberry (Solanum scabrum Mill.).
The present study sought to investigate the factors implicated in growth impairment of huckleberry (a leafy vegetable) under water stress conditions. To achieve this, seedlings of plant were subjected to control, mild stress and severe stress conditions for 30 days. Plant growth, plant water relation, gas exchange, oxidative stress damage, electrolyte leakage rate, mineral content and osmolyte accumulation were measured. Water deficit markedly decreased leaf, stem and root growth. Leaf photosynthetic rate was tremendously reduced by decrease in stomatal conductance under stress conditions. Malondialdehyde (MDA) content markedly increased under mild (82%) and severe (131%) stress conditions, while electrolyte leakage rate (ELR) increased by 59% under mild stress and 3-fold under severe stress. Mineral content in leafwas high in stressed plants, while proline content markedly increased under mild stress (12-fold) and severe stress (15-fold), with corresponding decrease in osmotic potential at full turgor and an increase in osmotic adjustment. These results suggest that maintenance of high mineral content and osmotic adjustment constitute important adaptations in huckleberry under water deficit conditions and that growth depression under drought stress would be mainly caused by increased electrolyte leakage resulting from membrane damage induced by oxidative stress.


High-temporospatial-resolution dynamic contrast-enhanced (DCE) wrist MRI with variable-density pseudo-random circular Cartesian undersampling (CIRCUS) acquisition: evaluation of perfusion in rheumatoid arthritis patients.
This study is to evaluate highly accelerated three-dimensional (3D) dynamic contrast-enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo-random variable-density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k-t SPARSE-SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti-tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow-up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm(3) and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28-ESR (r = -0.80, p < 0.05) and DAS28-CRP (r = -0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow-up (with DAS28-ESR r = -0.79, p < 0.05, and DAS28-CRP r = -0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses.


Interleukin-1 alpha: its possible roles in cancer therapy.
Our studies on recombinant human IL-1 alpha polypeptide were summarized with respect to molecular cloning, production, quantitative assay systems, antitumor activity, myelorestorative activity and augmentation of host resistance to infections. Recombinant human IL-1 alpha (18 kDa) was produced through the expression of the cloned human IL-1 alpha cDNA in Escherichia coli and purified to an endotoxin-free homogeneous polypeptide. The human IL-1 alpha inhibited dose-dependently the growth of syngeneic murine tumors transplanted in mice and completely regressed the tumors in some cases, and its antitumor activity was significantly enhanced in combination with indomethacin. The human IL-1 alpha accelerated the recovery of the numbers of peripheral leukocytes and neutrophils in a dose-dependent manner at a dose as low as 10 ng/mouse/day in myelosuppressed mouse model produced by administering anticancer chemotherapeutic drugs. The myelorestorative effect of IL-1 alpha was observed not only on leukocytes/neutrophils, but also on platelets in myelosuppressed mice. In addition, the human IL-1 alpha markedly augmented dose-dependently resistance of normal and leukopenic mice to various microbial infections. These results suggested that recombinant human IL-1 alpha might be useful for cancer therapy from the viewpoints of improving adverse effects such as myelosuppression caused by chemotherapy and/or radiation therapy and preventing infections. In addition, use of IL-1 alpha may permit more intensive chemo- and radiation therapies using higher doses. Finally, the antitumor activity of the IL-1 alpha itself may play an important role.


Predicting synergistic effects of resources and predators on foraging decisions by juvenile Steller sea lions.
Many theoretical and experimental studies suggest that synergistic interactions between resources and predators influence foraging decisions and their fitness consequences. This framework, however, has been ignored almost completely by hypotheses on causes of the population decline of Steller sea lions (SSLs) (Eumetopias jubatus) in western Alaska. By comparing predictions from a dynamic state variable model to empirical data on the behaviour of individuals instrumented with satellite-linked time-at-depth recorders, we develop and find preliminary support for the hypothesis that, during winter in Prince William Sound, juvenile SSLs (a) underutilise walleye pollock, a predictable resource in deep strata, due to predation risk from Pacific sleeper sharks, and (b) underutilise the potential energy bonanza of inshore aggregations of Pacific herring due to risk from either killer whales, larger conspecifics, or both. Further, under conditions of resource scarcity-induced by overfishing, long-term oceanographic cycles, or their combination-trade-offs between mortality risk and energy gain may influence demographic parameters. Accordingly, computer simulations illustrated the theoretical plausibility that a decline of Pacific herring in shallow strata would greatly increase the number of deep foraging dives, thereby increasing exposure to sleeper sharks and mortality rates. These results suggest that hypotheses on the decline of SSLs should consider synergistic effects of predators and resources on behaviour and mortality rates. Empirical support for our model, however, is limited and we outline tasks for empirical research that emerge from these limitations. More generally, in the context of today's conservation crises, our work illustrates that the greater the dearth of system-specific data, the greater the need to apply principles of behavioural ecology toward the understanding and management of large-scale marine systems.


Phosphorus management in cropping systems of the Paris Basin: From farm to regional scale.
The sustainability of phosphorus (P) fertilization in cropping systems is an important issue because P resources on earth are limited and excess P in soils can lead to ecological damage such as eutrophication. Worldwide, there is an increasing interest in organic farming (OF) due to its good environmental performance. However, organic cropping systems are suspected of generating negative P budgets, which questions their ability to provide sustainable P management. The design of agricultural systems at a broader scale also largely influences the shape of the P cycle and the possibility of its recycling to cropland. In this context, the aim of this study was to assess the relative influence of (i) OF versus conventional farming (CF) practices and (ii) the structure of agro-food systems at the regional scale, on P cycling and availability on cropland. For this purpose, we examined P budgets and soil P status of 14 organic and conventional cropping systems in commercial farms located in the Paris Basin. Available P was analyzed using two different methods: resin P and Olsen P. The results revealed no significant differences between CF and OF in available P stocks. Phosphorus budgets were always negative and significantly lower in CF systems, indicating that P was mined from soil reserves. In parallel, we estimated P budgets over cropland in all French regions for two distinct periods, 2004-2014 and 1970-1981, and showed that specialized intensive cropping systems in the Paris Basin led to a high, positive P budget in the latter period. However, this trend was reversed in the 2004-2014 period due to a sharp reduction of the mineral fertilizer application rate. The shift from very high P budgets to much lower and sometimes negative P budgets would not be a threat for agriculture due to the current high level of Olsen P in these regions, which was consistent with our measurements at the plot scale. Overall, these results suggest that OF would not lead to more P deficiency than CF. Instead, they emphasize that sustainable P management not only depends on farmers' choices but mainly on the structure and specialization of agro-food systems.


Effect of Al and Y2O3 on Mechanical Properties in Mechanically Alloyed Nanograin Ni-Based Alloys.
The effects of aluminum and Y2O3 on the mechanical properties in nano grain Ni-based alloys have been investigated. The test specimens are prepared by mechanical alloying at an Ar atmosphere. The addition of Y2O3 and Al may cause an increase in the tensile strength at room temperature, 400 °C and 600 °C. However, it was confirmed that the increase of tensile strength at room temperature and 400 °C was predominantly caused by addition of Y2O3, while that at 600 °C was mainly due to addition of Al. These results can be attributed to the dispersion strengthening of Y2O3, preventing the formation of Cr2O3 and the change of fracture mode at 600 °C by the addition of Al.


Clinical evaluation of a novel head protection system for interventional radiologists.
A novel two-part protective system consisting of a modified thyroid collar and a head protection is intended to reduce the radiation dose to the examiners head during fluoroscopy-guided interventions. In this pilot study, we tested this protection system under real-life conditions in general radiological and neuroradiological interventions. Two sets of the protection system (set A and B) were equipped with 12 thermoluminiscence detectors (TLD). For simultaneous measurement of radiation exposure and dose-reduction, each six TLDs were fixed to the inner side and on the corresponding outer side of the protection system. Set A was used exclusively for general radiological interventions and set B exclusively for neuroradiological interventions. To compare the staff exposure in general radiology and neuroradiology, dose values were normalized to a DAP of 10 000 µGy∙m2. The sets were tested during 20 general radiological interventions and 32 neuroradiological interventions. In neuroradiology, the mean normalized radiation exposure was 13.44 ± 1.36 µSv/10000 µGy∙m2 at the head protection and 22.27 ± 2.09 µSv/10 000 µGy∙m2 at the thyroid collar. In general radiology, the corresponding results were 29.91 ± 4.19 µSv/10 000 µGy∙m2 (head protection) and 68.07 ± 17.25 µSv/10 000 µGy∙m2 (thyroid collar). Thus, mean dose exposure was 2.5 times higher in general radiological interventions (p = 0.016). The use of the protection system resulted in a mean dose reduction of 81.2 ± 11.1 % (general radiology) and 92.1 ± 4.2 % (neuroradiology; p = 0.016). Fluoroscopy-guided interventions lead to significant radiation exposure of the head area for the examiner. The novel protection system tested led to a significant dose reduction of 80-90%, depending on the type of intervention.


Proliferation of human peripheral blood mononuclear cells during calcium channel blockade.
To evaluate the role of intracellular calcium and particularly Ca2+ uptake in the initiation of lymphocyte mitogenesis, the effect of mibefradil--which blocks both L- and T-type calcium channels with a more selective blockade of T-type channels--on the proliferation of human peripheral blood mononuclear cells (PBMC) is compared with the effect of nifedipine, which blocks only the L-type calcium channel. The rate of 3H-thymidine, 3H-uridine, and 3H-leucine incorporation into control and concanavalin A-stimulated PBMC in the presence or absence of the calcium channel blockers mibefradil or nifedipine (1, 10, or 50 micromol/L), and of the intracellular calcium antagonist TMB-8 or the calmodulin antagonist W-7 (1, 10, 25, or 50 micromol/L) was assayed in cells cultured for 3 days. The cellular cytotoxicity and the cell number in growing cultures was also determined in mibefradil- or nifedipine-treated control or stimulated cells. Mibefradil and nifedipine reduced the cell number and the 3H-thymidine, 3H-uridine, or 3H-leucine incorporation or the de novo DNA, RNA, or protein synthesis in control and concanavalin A-stimulated human PBMC in a concentration-dependent manner. Mibefradil exhibited a more pronounced inhibition than nifedipine. The inhibitory effect of mibefradil or nifedipine on DNA synthesis was dependent upon the timing of treatment with the drugs. The inhibitory effect of mibefradil or nifedipine on the lymphoproliferative response was nearly abolished if the drugs were added 20 h after cell stimulation. A markedly reduced inhibitory effect was found when mibefradil or nifedipine were added 1 to 7 h after cell stimulation. However, regardless of time of addition, TMB-8 and W-7 caused a persistent inhibition of the proliferation of human PBMC. Our data show that mibefradil had a more pronounced inhibitory effect on the proliferation of human PBMC than nifedipine and that this inhibitory effect on de novo DNA synthesis was dependent upon the timing of treatment with both drugs. Mibefradil and nifedipine also reduce RNA and protein synthesis in human PBMC. Therefore, administration of these calcium channel blockers to inhibit cellular proliferation might be most beneficial at anatomic sites where cellular proliferation is not already an active process, while being ineffective in the presence of ongoing active proliferation, as suggested by some prospective studies.


Lead staining in the Golgi complex.
Lead ions at similar concentrations to those used for Gomori type phosphatase localization stain some parts of the vacuolar system, particularly compartments of the Golgi complex (GC) and isolation envelopes (im) in a characteristic way in both vertebrates and invertebrates. After fixation in 2.5% glutaraldehyde, lead citrate in acetate or aspartate buffer (pH 5.5-7.2) leaves the contents of GC cisternal compartments with a fine particulate stippling. In the fat body of Calpodes ethlius and in mouse pancreas the staining is faint but definite without further enhancement of contrast, although it is easily overlooked after section staining. The distribution of lead stain differs from that of the lead phosphate precipitated after Gomori type acid phosphatase reactions. Whereas lead stain may be in all GC and im compartments, acid phosphatase is restricted to the innermost saccules and nearby vacuoles. The compartment specific staining by led also differs from the generalized staining in all compartments given by uranyl. Thus the contents of luminal membrane surfaces of some parts of the vacuolar system can be characterized by their ability to bind lead. In cells where protein synthesis has been blocked by cycloheximide, secretory vesicles are absent and the RER and GC from the generalized staining in all compartments given by uranyl. Thus the contents of luminal membrane surfaces of some parts of the vacuolar system can be characterized by their ability to bind lead. In cells where protein synthesis has been blocked by cycloheximide, secretory vesicles are absent and the RER and GC from the generalized staining in all compartments given by uranyl. Thus the contents of luminal membrane surfaces of some parts of the vacuolar system can be characterized by their ability to bind lead. In cells where protein synthesis has been blocked by cycloheximide, secretory vesicles are absent and the RER and GC cisternae are devoid of uranyl stainable material. However, lead staining and acid phosphatase activity in the GC continue. We presume that they mark the environment within these cisternae rather than the proteins passing through them. This environment is itself not static. Several observations suggest that the function of cisternae that is detectable by lead staining is temporally discontinuous and related to a stage of maturation or development. Only early stage ims stain: the staining ceases by the beginning of autophagy after hydrolytic enzymes are presumed to have been added. Condensing vacuoles cease to stain as the central core crystallizes out. Stain may be absent from one or two GC saccules at any position in the stack as though the phase of lead staining (or lack or it) can move progressively through the system. We conclude that in studies characterizing components of the vacuolar system it is necessary to separate those that mark transient occupants of a compartment from those that mark the compartment itself. Both may vary temporally independently from one another.


Effect of Corynebacterium parvum on hemopoietic stem-cell kinetics.
The intravenous administration of 548 microgram of killed Corynebacterium parvum (C. parvum) into C57BL mice leads to a significant decrease in the number of bone-marrow colony-forming-units in spleen (CFUs) as early as 12 h after the injection of the bacterium. This decrease persisted in varying degrees for 3 weeks. After an initial fall at 24 h, the splenic CFUs exhibited a rapid expansion and reached values 10 times higher than the control range on the ninth day. A significant rise in the number of circulating CFUs, reaching a first peak at 2 h and a second one on the fifth day, was also observed. The proliferative status of femoral CFUs was increased at 48 and 72 h, while that of splenic CFUs presented a significant increase only 48 h after the injection of C. parvum. The sequence of events which were observed in these experiments indicates that an accelerated migration of hemopoietic stem cells from bone marrow to spleen via the blood circulation has to take place.


Central nervous system complications of cancer therapy.
As more effective therapies prolong the survival of patients with cancer, therapy-related toxicities, particularly those affecting the central nervous system (CNS) become increasingly important. CNS complications can cause significant morbidity and can limit the dose or duration of otherwise effective treatments. Because effects on the CNS are disabling and often permanent and treatments remain limited, it is important that clinicians recognize the effects of cancer therapy on the CNS. Cytotoxic chemotherapy and radiation are well-known causes of neurotoxicity, but there is increasing recognition that novel therapies are also sources of adverse effects on the CNS. This review highlights the CNS complications that result from radiation, chemotherapy, and novel therapeutics.


Characteristics of L-carnitine import into heart cells.
L-carnitine is an essential cofactor for the transport of fatty acids across the mitochondrial membranes. L-carnitine can be provided by food products or biosynthesized in the liver. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as the skeletal muscle and the heart. The intracellular transport of L-carnitine into the cell requires specific transporters and today, several of these have been characterized. Most of them belong to the solute carrier family. Heart is one of the major target for carnitine transport and use, however basic properties of carnitine uptake by heart cells have never been studied. In this paper, the transport of L-carnitine by rat heart explants has been examined and the kinetic properties of this transport determined and compared to data obtained in skeletal muscle explants. As in muscle, L-carnitine uptake by heart cells was shown to be dependent on sodium and was inhibited by L-carnitine analogues. Molecules known to interact with the skeletal muscle L-carnitine transport were studied in the heart. While trimethyl hydrazinium propionate (THP) was shown to fully inhibit the L-carnitine uptake by muscle cells, it remained inefficient in inhibiting the L-carnitine uptake by heart cells. On the other hand, compounds such as verapamil and AZT were both able to inhibit both the skeletal muscle and the cardiac uptake of L-carnitine. These data suggested that the muscle and heart systems for L-carnitine uptake exhibited different systems of regulation and these results have to be taken in consideration while administrating those compounds that can alter l-carnitine uptake in the muscle and the heart and can lead to damage to these tissues.


Analysis of different preferences for the EU's regulatory options for endocrine disruptor identification criteria using argumentation theory.
What criteria are most suitable to identify endocrine disrupting substances (EDSs) for regulatory purposes in the EU? The results of the European Commission's public consultation, as part of the process to establish identification criteria for EDSs, show that different regulatory options are supported. Some respondents prefer an option including hazard characterization considerations, whereas others prefer an option that avoids these considerations and introduces several hazard-identification based weight-of-evidence categories. In this study, the argumentation underlying the different preferences for identification criteria are analyzed and compared using pragma-dialectical argumentation theory (PDAT). All responses of non-anonymous, national governments that submitted a response in English (n = 17) were included. Responses of other stakeholder organizations were included if a Google News search returned an opinionated presence in the media on the subject (n = 9). Five topical themes and 21 underlying issues were identified. The themes are 1) mechanistic understanding of EDSs, 2) regulatory considerations related to the identification of EDSs, 3) consistency with existing regulatory frameworks, and 4) evaluations of specific issues related to a category approach and 5) related to including potency. We argue that two overarching (implicit) 'advocacy coalitions' can be discerned, that adopted contrasting positions towards the identified themes and issues. Among these 'coalitions', there appears to be consensus about the necessity of having 'science-based' criteria, though different perspectives exist as to what the most accurate mechanistic understanding of EDSs entails. To move the discussion forward, we argue that a societal dialogue would be beneficial, where EDS science and regulation are discussed as interrelated themes.


Small-angle X-ray scattering in the era of fourth-generation light sources.
Recently, fourth-generation synchrotron sources with several orders of magnitude higher brightness and higher degree of coherence compared with third-generation sources have come into operation. These new X-ray sources offer exciting opportunities for the investigation of soft matter and biological specimens by small-angle X-ray scattering (SAXS) and related scattering methods. The improved beam properties together with the advanced pixel array detectors readily enhance the angular resolution of SAXS and ultra-small-angle X-ray scattering in the pinhole collimation. The high degree of coherence is a major boost for the X-ray photon correlation spectroscopy (XPCS) technique, enabling the equilibrium dynamics to be probed over broader time and length scales. This article presents some representative examples illustrating the performance of SAXS and XPCS with the Extremely Brilliant Source at the European Synchrotron Radiation Facility. The rapid onset of radiation damage is a significant challenge with the vast majority of samples, and appropriate protocols need to be adopted for circumventing this problem.


Construction of an expression vector for human papillomavirus type 16 E7-glutathione S transferase fusion protein.
An expression vector for human papillomavirus type 16 (HPV 16) E7-glutathione S transferase fusion protein was constructed. The E7 gene was confirmed by southern blot analysis with a digoxygenin 11-dUTP labeled and simultaneously amplified E7 DNA probe by polymerase chain reaction (PCR). The fusion protein was expressed in E. coli, recovered as inclusion bodies, and was confirmed by western blot analysis using a monoclonal antibody against HPV 16-E7 protein. A polyclonal antibody against the HPV 16-E7 protein was raised in the serum of mice hyper-immuned with the fusion protein. This antibody will be available for screening of patients with cervical cancer.


The effect of vitamin D status on risk factors for cardiovascular disease.
Vitamin-D-related pathways are implicated in various endocrine, inflammatory and endothelial functions. An estimated 1 billion people in the world have vitamin D deficiency or insufficiency, and undiagnosed vitamin D deficiency is common. Vitamin D deficiency is associated with substantial increases in the incidence of hypertension, hyperlipidaemia, myocardial infarction and stroke, as well as in diseases such as chronic kidney disease and type 2 diabetes. Low vitamin D levels also upregulate the renin-angiotensin-aldosterone system, increase inflammation and cause endothelial dysfunction. However, the role of vitamin D deficiency in cardiovascular morbidity and mortality is an emerging and hotly debated topic. Epidemiological studies suggest an association between low vitamin D levels and risk factors for cardiovascular disease, but a causal relationship has not been established, and clinical trials and meta-analyses have not demonstrated convincing evidence that vitamin D therapy improves cardiovascular outcomes. Some evidence suggests that vitamin D status is a biomarker of lifestyle, since unhealthy and sedentary lifestyles are associated with vitamin D insufficiency or deficiency and are also risk factors for cardiovascular complications.