[Results of preclinically placed thoracic drainages].
Thorax injuries are to be found in approximately 78 % amongst all victims of accidents. Moreover they implicate an increase in mortality rate. Consequently an adequate contemporary treatment has to begin preclinically, even if the conditions are less comfortable than in a clinical setting. Emergency doctors need to be familiar with the placement of chest tubes. From 01.01.2007 to 31.12.2010 emergency doctors of the rescue helicopter site Christoph 20 had to place chest tubes directly at the scene of an accident in 49 patients. These patients were now reidentified and their clinical course reevaluated. By means of apparative diagnostics it was possible to analyse the location of the tips of the tubes. A comparison of the patient outcome versus the quality of preclinical thoracic drainage could be made. The preclinical placement of a chest tube became necessary mainly because of a blunt thoracic trauma. This was predominantly related to victims of traffic accidents, whereas male victims clearly dominated. 42 of those patients received further treatment at the Klinikum Bayreuth, enabling an analysis of the tube locations by CT scans. Six patients had been drained on both sides, contributing to the 48 tube tips that could be examined concerning their location. Of the 48 chest tubes 46 had been placed from a lateral approach. The ventral access according to Monaldi had only been chosen in two cases. Altogether nine incorrect placements, mainly within the right interlobe gap, were detected. The study collective showed a significant preference to the lateral approach when placing a chest tube at the emergency scene of an accident. In total a prevalence of 19 % incorrect placements could be revealed, meaning the chest tube had either been placed within the lung parenchyma, the interlobe gap or extrathoracically. Concerning the patient outcome no statistically significant difference regarding the clinical course after incorrect chest tube placement could be identified. The omission of an indicated preclinical thoracic drainge is certainly a more serious error than its incorrect placement with more serious consequences.


How sustainable is the nitrogen management in Brazil? A sustainability assessment using the Entropy Weight Method.
Nitrogen pollution is one of Brazil's most threatening and challenging environmental problems, caused mainly by productive activities aimed at meeting the demand of food, energy, and housing by a fast-growing population. Sustainable nitrogen management involves optimizing the beneficial effects of reactive nitrogen (Nr) use and, at the same time, mitigating the negative impacts of its excess on the environment and human health. Here we conduct an assessment of nitrogen sustainability in Brazil from 2000 to 2018 applying the Entropy Weight Method (EWM) to a set of nitrogen-related indicators within four subsystems: environmental, economic, social, and institutional. Our research objectives are to determine an overall Nitrogen Sustainability Index and discuss the relevance of indicators linked to the main anthropogenic sources of nitrogen pollution. By our analysis, the following indicators play a key role in determining nitrogen sustainability levels in the country: political stability, fertilizer consumption, population growth, and investments in water and sanitation. Our findings suggest that political and institutional concerns are greatly impacting sustainable actions towards nitrogen management, leading Brazil to reach only a weak-to-basic level of sustainability in the studied period. We highlight that neglecting the problems caused by the unsustainable nitrogen management can increase environmental, economic, and social issues, and jeopardize the achievement of the Sustainable Development Goals (SDGs). In addition to fostering of sustainability goals on the agriculture and energy sectors from the environmental, socioeconomic, and political perspectives, the importance of this assessment lies in supporting governments, policymakers, and civil society to develop sustainable nitrogen roadmaps to significantly reduce nitrogen waste by 2030, as outlined in the 2019 Colombo Declaration on Sustainable Nitrogen Management backed by the UN Environment Programme.


Sapucaia nut: Morphophysiology, minerals content, methodological validation in image analysis, phenotypic and molecular diversity in Lecythis pisonis Cambess.
Sapucaia or Lecythis pisonis Cambess. is an ornamental tree that produces edible, tasty, and nutritious nuts, and can be used for timber production. Sapucaia has potential as a functional food, owing to optimal nutritional and particularly Se levels. The present study sought to characterize the seeds of 21 sapucaia matrices from forest remnants of a neotropical hotspot (Atlantic Forest) and farms in two Brazilian states. Biometrics, germination, vigor, lignin content in the teguments, minerals content, and phenotypic and molecular diversity were analyzed. The seeds of matrices 16 and 21 were the most vigorous. Nuts from matrices 21 and 17 contained the highest amounts of Se. Matrices 5, 8, and 21 were the most phenotypically distant; whereas matrix 21 was the most genetically distant. Importantly, we validated a new non-destructive and efficient X-ray-based methodology for internal and densitometric analysis of sapucaia seeds, and demonstrated a high genetic divergence among matrices.


Phosphorylation by cell surface protein kinase of bovine and human fibrinogen and fibrin.
Human and bovine fibrinogen as well as fibrin are shown to be phosphorylated by Co631 (monolayer, hamster) and RPL12 (suspension, chicken) cells by their surface protein kinase of the casein kinase II type. The phosphate label is introduced into the alpha-peptide. The kinase system phosphorylates serine residues and utilizes GTP equally well as ATP. The participation of intact cell surfaces indicates the possibility of phosphorylation of extracellular fibrinogen independently of the site of its biosynthesis.


Bedside biochemical monitoring of the penumbra zone surrounding an evacuated acute subdural haematoma.
We describe a penumbra zone with increased biochemical vulnerability in cerebral cortex underlying an evacuated acute subdural haematoma. Two microdialysis catheters were placed in this zone and one catheter was placed in the opposite, less injured hemisphere. The microdialysis perfusates were analysed bedside for glucose, pyruvate, lactate, glutamate, and glycerol. In the penumbra zone, but not in the opposite hemisphere, energy metabolism was seriously disturbed with signs of cell membrane degradation. During an adverse event (decrease in haemoglobin level, systemic blood pressure and cerebral perfusion pressure) the perturbation of energy metabolism increased in this zone. Energy metabolism recovered and the signs of cell membrane degradation disappeared after normalization of the physiological parameters. We use the term biochemical penumbra zone to describe an area with signs of energy failure and cell membrane degradation, which has a capacity to regain a normal metabolic pattern but also an increased vulnerability to secondary insults.


Prognostic factors in resected stage I non-small cell lung cancer with a diameter of 3 cm or less: visceral pleural invasion did not influence overall and disease-free survival.
Resection is the treatment of choice for patients with stage I non-small cell lung cancer. Stage I non-small cell lung cancer has been further subdivided into IA (T1N0M0, tumor size < or = 3 cm without visceral pleural invasion) and IB (T2N0M0, tumor size > 3 cm or any size with visceral pleural invasion). The aim of this study was to evaluate the prognostic factors in patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less. We retrospectively reviewed the clinicopathologic characteristics of 445 patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less who were treated at Taipei Veterans General Hospital between 1980 and 2000. Disease-free survival, overall survival, and their predictors were analyzed. The 5- and 10-year overall survivals were 61.4% and 40.0%, respectively. The 5- and 10-year disease-free survivals were 74.5% and 73.4%, respectively. Tumor size, smoking index, and number of mediastinal lymph nodes dissected were significant predictors for both disease-free survival (P = .009, P = .002, and P = .006, respectively) and overall survival (P = .004, P < .001, and P = .001, respectively) in multivariate analyses. Visceral pleural invasion did not influence overall survival or disease-free survival. Tumor size, smoking index, and number of mediastinal lymph nodes dissected were prognostic factors for both overall survival and disease-free survival in resected stage I non-small cell lung cancer with a diameter of 3 cm or less. Small tumors (<3 cm) of stage IB (T2N0M0) non-small cell lung cancer with visceral pleural invasion should be treated as T1 disease and not T2 disease.


Perceived Recovery and Self-Reported Functioning in Adolescents with Mild Traumatic Brain Injury: The Role of Sleep, Mood, and Physical Symptoms.
Purpose: To determine the contributions of anxiety, depressive, and concussion symptoms and sleep quality to self-perceived recovery in adolescents with concussion.Method: Adolescents aged 12-20 (n = 298) completed anxiety, depression, concussion symptoms, and sleep measures at an initial concussion clinic visit and three-month follow-up. At follow-up, they reported self-perceived recovery as percent back to normal.Results: Injury-related factors alone did not predict self-perceived recovery (R2Adj =.017, p =.074). More concurrent physical, mental health, and sleep symptoms explained 18.8% additional variance in poorer self-perceived recovery (R2Adj Change =.188, p <.05). Physical symptoms (Bstand = -.292) and anxiety (Bstand = -.260) accounted for the most variance in self-perceived recovery.Conclusion: Post-concussive symptoms, in particular anxiety and self-reported physical symptoms, seem to characterize protracted recovery. Self-perceived recovery as an outcome measure may provide a more holistic understanding of adolescents' experiences after concussion.


Jejunojejunal intussusception following jejunostomy closure: A case report.
Intussusception can occur anywhere in the small and large bowel, ileocolic intussusception is the most common type in adult and there are few reported cases of jejunojejunal intussusception. Here we report a case of jejunojejunal intussusception due to an iatrogenic lead point at the feeding jejunostomy closure site. In 2019 we received a 63-year-old female complaining of abdominal pain, constipation, and repeated vomiting for five days. On physical examination, she was dehydrated, in pain, and had a nasogastric tube that was draining bilious fluid. The abdomen was tender, there was a long midline incision with tension sutures at the lower of incision. CT of the abdomen showed ileoileal intussusception. Proper resuscitation and preoperative preparation were done. During exploratory laparotomy, there was jejunojejunal intussusception. The intussusception was reduced gently and completely. Resection of the lead point segment done with end to end anastomosis. The patient recovered uneventfully and discharged home on the 5th postoperative day. The patient followed up after one and three months with no complications. During the closure of the feeding jejunostomy site by hand-sewn technique, over invagination of the second (seromuscular) layer of the wall of the jejunum might become so thick at the site of the closure that it acts as a lead point for intussusception. We reported a case of such a scenario.


Core-shell starch as a platform for reducing starch digestion and saturated fat intake.
Ill-balanced diets, especially high-carbohydrate and high-fat diets, have led to an explosion of diabetes and cardiovascular diseases worldwide, posing great threats to human health. The structural design of functional foods can offer promising solutions to these afflictions. Here, we introduce a versatile core-shell starch made from food-grade starch and alcohol-soluble protein to reduce starch digestion and saturated fat intake. The fabrication of core-shell structure is realized through an anti-solvent method, assisted by electrostatic interaction, which is generalizable to starches and proteins from different sources and feasible for scale-up production. The protein shell imparts a higher gelatinization temperature and a lower pasting viscosity to the starch, suggesting restricted granule swelling, which leads to a reduced starch digestibility as proved by in vitro digestion studies. The hypoglycemic effect of core-shell starch is demonstrated in vivo. We also show that the application of core-shell starch can be extended to oil encapsulants and saturated fat replacers due to the impact of protein shell on the surface hydrophobicity of the starch. These results may advance the establishment of healthy diets and the tackling of diet-related diseases.


Practical application of wireless communication network multimedia courseware in college basketball teaching.
With the acceleration of informatization and the coverage of wireless networks, homes, conferences, schools and other places have a higher pursuit of the wireless transmission capabilities of electronic devices. Wireless screen transmission technology is used more frequently in life, work and study. This article mainly discusses the practical application of network multimedia courseware in college basketball teaching. This article first elaborates the teaching plan of multimedia courseware, including teaching content, teacher guidance, student learning and multimedia courseware. Secondly, the multimedia courseware of basketball tactics basic teaching is completed by using Flash mx2004 plug-in. After that, it specifically introduces the process of how to transmit basketball teaching content through multimedia equipment to the video network for students to learn under the wireless network environment. It emphasizes that the "wireless multimedia communication" course is an important course in the electronic information subject. Finally, through the teaching experiment, the accuracy of the multimedia teaching method was tested, and the validity of the courseware content was tested by the empirical validity evaluation method. At the same time, after the teaching experiment, in order to test the two groups of students' mastery of the basic coordination theory of basketball tactics, the basic coordination theory of basketball tactics was tested. The experimental group had 22 students with a score of 90 or more, accounting for 27.5%, and the control group had 13 students with a score of 90 or more, accounting for 16.5%. The results show that wireless network multimedia computer-assisted teaching has a positive effect on improving students' interest in learning.


Gestational hypertension, preeclampsia and intrauterine growth restriction induce dysregulation of cardiovascular and cerebrovascular disease associated microRNAs in maternal whole peripheral blood.
To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out. The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications. Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood.


Importance of three-dimensional geometric analysis in the assessment of the athlete's heart.
How the left ventricle remodels in response to a high-volume stimulus is important in evaluating the endurance athlete's heart. Marathoners and patients with isolated, moderate chronic compensated mitral regurgitation (MR) represent physiologic and pathologic forms of eccentric left ventricular (LV) remodeling in response to intermittent and chronic volume overload, respectively. Thus, in this study, magnetic resonance imaging with tissue tagging and 3-dimensional data analysis at rest were performed in 19 marathoners (mean age 39 ± 10 years, 47% women), 17 patients with isolated MR without coronary artery disease or medical therapy (mean age 46 ± 5 years, 53% women), and 24 controls (mean age 45 ± 8 years, 50% women). Marathoners and patients with MR had approximately 35% greater LV end-diastolic volume indexes, approximately 50% greater end-systolic volume indexes, and approximately 34% greater LV stroke volume indexes (p <0.0001) compared to controls. However, marathoners' hearts had increased long-axis length, while those of patients with MR did not differ from the hearts of controls. The hearts of patients with MR had greater LV global and apex sphericity compared to those of marathoners and controls (p <0.0001). Marathoners had normal LV mass/volume ratios and wall thicknesses, whereas these were significantly decreased in the MR group. In marathoners, the baseline LV work rate was similar to that in controls and higher in patients with MR compared to controls. In conclusion, marathoners' hearts achieve elevated stroke volume at rest with adherence to an elliptical shape defined by 3-dimensional geometry and mass/volume ratio. Thus, a comprehensive evaluation of LV geometry and mass/volume ratio may be important in the evaluation of the athlete's heart.


Xanthogranulomatous pyelonephritis: a critical analysis of 26 cases and of the literature.
Manifestations of xanthogranulomatous pyelonephritis in 26 patients closely mimicked those of neoplastic and other inflammatory renal parenchymal diseases. Middle-aged or older women were affected most often. Most patients presented with anemia, chronic febrile illness, a painful tender flank mass and recurrent urosepsis. Some features of nephrogenic hepatic dysfunction were present in 13 patients. Bacterial cultures of renal tissue were almost always positive but the spectrum differed considerably from that of the bladder urine. Urographically, a renal mass lesion was encountered in 62% of the patients, nephrolithiasis in 38% and a functionless kidney in 27%. Angiographically, none of the 4 mass lesions studied was distinguished from hypernephroma. Indeed, a correct preoperative diagnosis was made in only 1 instance. There were 3 stages of xanthogranulomatous pyelonephritis recognized. Treatment consisted of nephrectomy for diffuse or advanced stage disease or both (21 patients), excision of the diseased renal segment for localized and low stage disease (2 patients) and renal biopsy (3 patients). Xanthogranulomatous pyelonephritis did not recur but in some patients bacteriuria continued or hypertension developed.


Craniocaudal tumour extension in uterine cervical cancer on MRI compared to histopathology.
To assess the reliability of magnetic resonance imaging (MRI) for evaluation of craniocaudal tumour extension by comparing the craniocaudal tumour extension on the pre-operative MRI and post-operative hysterectomy specimen in patients with early stage uterine cervical cancer. After approval of the institutional review board was acquired, pre-operative MRI and hysterectomy specimen of 21 women with early stage cervical cancer were re-evaluated. The craniocaudal extension on MRI was measured separately by two experienced radiologists and compared with corresponding measurements from the hysterectomy specimen, which were re-evaluated by an experienced pathologist. Median craniocaudal extension of uterine cervical cancer on MRI was slightly smaller compared to histopathology (2.1 cm vs. 2.5 cm). The median underestimation was 0.4 cm (range -0.6 cm to 2.2 cm, mean 0.4 cm, standard deviation (SD) ±0.7 cm); Pearson's correlation was 0.83 (p < 0.001). In two patients (9%) MRI underestimated tumour craniocaudal extension by more than 1.8 cm. MRI represents the histopathological craniocaudal tumour extension in the majority of patients with early stage uterine cervical cancer, but with a systematic small underestimation of the real craniocaudal tumour extension.


Literacy and health research in Canada: where have we been and where should we go?
This article reviews current literature and research on literacy and health and identifies priorities for research on this topic in Canada. Information sources included documents found through an environmental scan, the Alpha Plus collection and a computer search of recent documents. The information was analyzed using a conceptual framework. The review found that low literacy has direct and indirect impacts on health. Families are at risk due to difficulty reading medication prescriptions, baby formula instructions and health and safety education materials. People with lower levels of literacy tend to live and work in less healthy environments. They have more difficulties obtaining employment and income security. Determinants of literacy include: education, early childhood development, aging, living and working conditions, personal capacity/genetics, gender and culture. Action is needed to improve literacy and health through a combination of health communication, education and training, community development, organizational development, and policy development. There is some evidence that such interventions can have a positive effect on health, particularly when combined with one another. Further program and policy development requires greater evidence and evaluation of existing initiatives, more cost/benefit analyses, more culturally specific studies, and greater attention to current social trends and needs.


Clonal diversity among erythromycin-resistant beta-haemolytic Streptococcus isolates in La Rioja, Spain.
To analyse clonal diversity in 72 erythromycin-resistant beta-haemolytic streptococci. Clonal relationships were studied for streptococci of groups A (GAS, n = 30), B (GBS, n = 34), C (GCS, n = 4) and G (GGS, n = 4) by means of PFGE. Streptococcal isolates were obtained from a 450-bed hospital in Spain during the following periods: GAS (1996-2001), GBS (1999-2001), GCS and GGS (1997-2000). Twenty-two of the 30 GAS isolates showed the M resistance phenotype and harboured the mef(A) gene. Five unrelated PFGE patterns were identified among these 22 GAS isolates. Sixteen of them, obtained during four different years of the study, showed one of the two predominant PFGE patterns. The remaining eight GAS isolates showed the MLSB resistance phenotype, and four unrelated PFGE patterns were detected. All but one erythromycin-resistant GBS showed the MLSB resistance phenotype, and an erm gene was identified in all cases [erm(B) or erm(A)]. Twenty-two unrelated PFGE patterns were demonstrated among 25 GBS with the MLSB resistance phenotype; the remaining eight MLSB GBS isolates could not be typed by PFGE. The eight erythromycin-resistant GGS and GCS isolates of this study presented seven unrelated PFGE patterns. GGS and GCS strains showed an MLSB resistance phenotype and had the erm(A) gene. High clonal diversity was detected in this series of erythromycin-resistant GBS, whereas lower diversity was seen in the GAS isolates.


Ofloxacin induces etiolation in Welsh onion leaves.
Antibiotic pollution has become an important global issue, and ofloxacin (OFL) is widely used worldwide. However, little is known about the potential adverse effects of OFL on plants. We assessed the toxic effects of OFL on Welsh onion and explored its toxicity mechanism. The leaf pigment content increased in 0.1 mg/L of OFL but decreased in a dose-dependent manner (0.5-2 mg/L OFL) until leaf etiolation. The ultrastructure of leaves showed that the treatment of 2 mg/L OFL produced significant toxicity. Furthermore, photosynthetic and fluorescence parameters were negatively affected by OFL treatment. The photosynthetic electron transport chain was significantly inhibited by OFL treatment, especially between QA and QB. The hydrogen peroxide and malondialdehyde content also increased with OFL concentration, indicating that antioxidant enzymes' role in antibiotic response is limited. In conclusion, OFL can damage chloroplasts by promoting ROS accumulation, which results in the etiolation of Welsh onion leaves.


Oxygen binding to partially nitrosylated hemoglobin.
Reactions of nitric oxide (NO) with hemoglobin (Hb) are important elements in protection against nitrosative damage. NO in the vasculature is depleted by the oxidative reaction with oxy Hb or by binding to deoxy Hb to generate partially nitrosylated Hb (Hb-NO). Many aspects of the formation and persistence of Hb-NO are yet to be clarified. In this study, we used a combination of EPR and visible absorption spectroscopy to investigate the interactions of partially nitrosylated Hb with O2. Partially nitrosylated Hb samples had predominantly hexacoordinate NO-heme geometry and resisted oxidation when exposed to O2 in the absence of anionic allosteric effectors. Faster oxidation occurred in the presence of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate (IHP), where the NO-heme derivatives had higher levels of pentacoordinate heme geometry. The anion-dependence of the NO-heme geometry also affected O2 binding equilibria. O2-binding curves of partially nitrosylated Hb in the absence of anions were left-shifted at low saturations, indicating destabilization of the low O2 affinity T-state of the Hb by increasing percentages of NO-heme, much as occurs with increasing levels of CO-heme. Samples containing IHP showed small decreases in O2 affinity, indicating shifts toward the low-affinity T-state and formation of inert α-NO/β-met tetramers. Most remarkably, O2-equilibria in the presence of the physiological effector DPG were essentially unchanged by up to 30% NO-heme in the samples. As will be discussed, under physiological conditions the interactions of Hb with NO provide protection against nitrosative damage without impairing O2 transport by Hb's unoccupied heme sites. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.


Increasing inclusivity in precision medicine research: Views of deaf and hard of hearing individuals.
Deaf/hard of hearing (HoH) individuals can benefit from precision medicine research (PMR) but are underrepresented in mainstream health research and may experience barriers to participation. Understanding their views and concerns about PMR can inform processes to foster inclusion in future studies and reduce health disparities. We administered an online disability-accessible survey to explore perceptions of PMR among, inter alia, deaf/HoH individuals. Questions included willingness to participate, interest in results, and barriers and facilitators to participation. Analyses describe results for participants who self-identified their primary condition as being deaf/HoH and compared results for key demographic characteristics. A total of 267 deaf/HoH participants completed the survey. Interest in PMR was high, although many reported inaccessible facilities and information about medical research; 51% reported that communication with health professionals is a barrier. Concerns about harm, lack of access to benefits, misinformed allocation decisions, and limited disability-relevant knowledge among researchers and health care providers were significant. Differences across racial, ethnic, and sex groups were observed and are discussed. Strategies to remove barriers to participation of deaf/HoH individuals in PMR are suggested. Distrust is a major challenge for cohort diversity, and research is needed to identify measures to increase the trustworthiness of PMR endeavors.


Changes in Population-Level and Institutional-Level Prescribing Habits of Radioiodine Therapy for Papillary Thyroid Cancer.
Background: In the past two decades, new evidence and guidelines have emerged to refine recommendations for the use of radioactive iodine (RAI) therapy after thyroidectomy for cancer. We aim to describe national trends in RAI utilization, assess the impact of individual hospitals on RAI utilization, and examine whether variation in prescribing habits has declined over time. Methods: The National Cancer Database (NCDB) was queried from 2004 to 2016 for patients with papillary thyroid cancer (PTC) who received total thyroidectomy. Trends were analyzed using Joinpoint analysis. Hospital-specific effects and variation in prescribing habits were assessed through a hierarchical, mixed regression model. Results: RAI utilization declined from 61.0% in 2004 to 43.9% in 2016. RAI use declined most profoundly in patients with T1a, N0/X, M0 PTC without extrathyroidal extension (34.8% in 2004 to 9.5% in 2015), but continues to be used commonly in patients with advanced disease for whom it is routinely recommended (73.4% in 2004 to 72.0% in 2015). Furthermore, ∼80% of hospitals in 2016 utilized at or below the median utilization rate in 2006. Variation in RAI utilization across hospitals decreased by ∼50% from 2004 to 2016 (Levene's test p < 0.001), with a significant decline (p = 0.002) in the variation after 2012 (confidence interval: 2010 to 2014). Conclusions: Recommendations for whom to prescribe RAI appear to have impacted both the number of patients receiving RAI and the variation in prescribing habits across hospitals. Hospital selection has contributed less to the probability of receiving RAI over time.


Selective induction of apoptosis through activation of caspase-8 in human leukemia cells (Jurkat) by dandelion root extract.
Dandelion extracts have been used in traditional Native American Medicine and Traditional Chinese Medicine (TCM) for treatment of leukemia and breast cancer; however, the mechanism of action remains unknown. Today, DRE is mainly marketed for management of gastrointestinal and liver disorders. The current study aims to determine the anti-cancer activity of dandelion root extract (DRE) against human leukemia, and to evaluate the specificity and mechanism of DRE-induced apoptosis. The effect of DRE on cell viability was evaluated using the colorimetric-based WST-1 assay. Apoptotic cell death was monitored by nuclear condensation and confirmed by exposure of phosphatidylserine to outer leaflet of plasma membrane. Activation of caspases was detected using a fluorogenic substrate specific to either caspase-8 or -3. Loss of mitochondrial membrane potential was observed by microscopy using JC-1 dye. The apoptotic effect of DRE was also evaluated on a dominant-negative FADD (Fas-associated death domain) cell line and non-cancerous peripheral blood mononuclear cells (PBMCs). Aqueous DRE effectively induces apoptosis in human leukemia cell lines in a dose and time dependent manner. Very early activation of caspase-8 and the subsequent activation of caspase-3 indicate that DRE may be inducing extrinsic or receptor-mediated apoptosis. Caspase inhibition rendered this extract ineffective, thus DRE-induced apoptosis is caspase-dependent. Moreover, the dominant-negative FADD cells that are unable to form a complete DISC (death-inducing signaling complex) were resistant to DRE treatment, which further confirms our hypothesis that DRE induces receptor-mediated apoptosis. Interestingly, non-cancerous peripheral blood mononuclear cells (PBMCs) exposed to aqueous DRE under the same treatment conditions as leukemia cells were not significantly affected. Our results suggest that aqueous DRE contains components that act to induce apoptosis selectively in cultured leukemia cells, emphasizing the importance of this traditional medicine and thus presents a potential novel non-toxic alternative to conventional leukemia therapy.


Nucleotide sequence of XhoI O fragment of ectromelia virus DNA reveals significant differences from vaccinia virus.
The nucleotide sequence of the 3913 base pair XhoI O fragment located in an evolutionary variable region adjacent to the right end of the genome of ectromelia virus (EMV) was determined. The sequence contains two long open reading frames coding for putative proteins of 559 amino acid residues (p65) and 344 amino acid residues (p39). Amino acid database searches showed that p39 is closely related to vaccinia virus (VV), strain WR, B22R gene product (C12L gene product of strain Copenhagen), which belongs to the family of serine protease inhibitors (serpins). Despite the overall high conservation, differences were observed in the sequences of p39, B22R, and C12L in the site known to interact with proteases in other serpins, suggesting that the serpins of EMV and two strains of VV may all inhibit proteases with different specificities. The gene coding for the ortholog of p65 is lacking in the Copenhagen strain of vaccinia virus; the WR strain contains a truncated variant of this gene (B21R) potentially coding for a small protein (p16) corresponding to the C-terminal region of p65. p65 is a new member of the family of poxvirus proteins including vaccinia virus proteins A55R, C2L and F3L, and a group of related proteins of leporipoxviruses, Shope fibroma and myxoma viruses (T6, T8, T9, M9). These proteins are homologous to the Drosophila protein Kelch involved in egg development. Both Kelch protein and the related poxvirus proteins contain two distinct domains. The N-terminal domain is related to the similarly located domains of transcription factors Ttk, Br-C (Drosophila), and KUP (human), and GCL protein involved in early development in Drosophila. The C-terminal domain consists of an array of four to five imperfect repeats and is related to human placental protein MIPP. Phylogenetic analysis of the family of poxvirus proteins showed that their genes have undergone a complex succession of duplications, and complete or partial deletions.


How cells build totipotency and pluripotency: nuclear, chromatin and transcriptional architecture.
Totipotent and pluripotent cells display different degrees of cellular plasticity. After fertilization, embryonic cells transit naturally from a totipotent to a pluripotent state. Major changes in nuclear architecture, chromatin mobility and gene expression occur during this transition. In particular, nuclear architecture has recently emerged as a potential regulator of heterochromatin formation in the early embryo. Future research should address whether a causal, functional link between nuclear organization and gene regulation is a general theme during reprogramming and the formation of pluripotent cells.


Peritoneal inclusion cysts in patients affected by Crohn's disease: magnetic resonance enterography findings in a case series.
Peritoneal inclusion cystarises when fluid produced by ovary is trapped within peritoneal adhesions. In this article, we describe a case series of patients affected by Crohn's disease, undergoing to magnetic resonance enterography, in whom it was possible not only to monitor the pathological findings of small bowel but also to primarily diagnose the presence of peritoneal inclusion cysts. The current knowledge of peritoneal inclusion cyst concomitant to Crohn's disease is still limited, often leading radiologists to misdiagnose it.


Metabolic responses of the green microalga Dunaliella salina to silver nanoparticles-induced oxidative stress in the presence of salicylic acid treatment.
In the present study, the biochemical responses and antioxidant enzymes activity of the Dunaliella salina, a green microalga, to the interaction of silver nanoparticles (AgNPs) and salicylic acid (SA) were investigated. Algal suspensions in the phase of logarithmic growth were subjected to the concentrations of 0, 5, 15, and 25 pM AgNPs with or without 1 mM SA. AgNPs level of 25 pM declined cell division but highly accumulated levels of chlorophyll, β-carotene, proteins, free amino acid, carbohydrates, and hydrogen peroxide, which was associated with enhanced the activity of proteolysis, lipid peroxidation, and antioxidant enzymes. SA-treated cells at 25 pM AgNPs improved cell growth but declined the activities of antioxidant enzymes and proteolytic along with a lower accumulation of metabolites except β-carotene relative to untreated controls. These results suggest that AgNPs treatment induce oxidative stress in D. salina cells, which tolerated by alga through the metabolic modifications and accumulating β-carotene, while SA induces AgNPs tolerance by the mechanisms that direct carbon flux to growth and β-carotene biosynthesis rather than the antioxidant enzymes or osmoprotectant metabolites.


Uterine artery pseudoaneurysm: unusual cause of delayed postpartum hemorrhage.
We describe a case of uterine artery pseudoaneurysm in a 21-year-old woman with postpartum hemorrhage. This condition is easily diagnosed with duplex Doppler sonography and can be treated with embolization, but only if delayed postpartum hemorrhage is considered in the differential diagnosis.


Very high-dose cisplatin-induced ototoxicity: a preliminary report on early and long-term effects.
Acute and subacute audiometric hearing changes were evaluated in 12 patients receiving 35 courses of very high-dose (vhd) cisplatin (200 mg/m2 per course) in hypertonic saline at 4 or 8-week intervals. Audiogical evaluations were performed both before and immediately after each course of chemotherapy, and again after the discontinuation of treatment. A significant drop of the mean hearing threshold (P less than 0.01) at high frequencies was observed even within 48 h from the end of the first course of therapy, with 50% of the patients presenting a hearing loss of more than 15 dB. At the same total dose (200 mg/m2), one course of this regimen provided an incidence of hearing loss of more than 15 dB, which was four times greater than that reported with two courses of standard-dose regimens. The incidence and severity of the hearing impairment progressed further with subsequent courses of chemotherapy. Compared with baseline levels, most patients (75%) receiving at least two courses had a moderate to severe hearing loss, especially involving 4 and 8 kHz. At the end of treatment, 33% of the patients complained of a nondisabling functional hearing impairment. No recovery occurred after chemotherapy had been discontinued for 9-28 weeks. At this dose level cisplatin is markedly ototoxic. The use of hypertonic saline and vigorous hydration are effective means of minimizing the risk of nephrotoxicity, but seem to have no effect on cisplatin-related ototoxicity.


Time-course effects of human recombinant luteinizing hormone on porcine Leydig cell specific differentiated functions.
Since recombinant hormones are considered as safer and more reliable in their bioactivity than extractive hormones, the recently available human recombinant luteinizing hormone (r-hLH), will probably replace hCG in the near future, for clinical purposes. This prompted us to investigate whether or not, and by which mechanisms, r-hLH can induce a desensitization of signal transduction and/or an up-regulation of steroidogenic capacity in Leydig cells. The effects of a 30 min to 24 h exposure to r-hLH (10(-9) M) on the differentiated functions of cultured immature porcine Leydig cells were studied by measuring the following parameters: LH/hCG receptor number and mRNA, hCG-, cholera toxin- and forskolin-induced cAMP production, G protein alphas subunit content of the membrane, hCG-, cholera toxin-, forskolin-, 8Br-cAMP-, 22R-OH-cholesterol-, progesterone-, 170H-progesterone-, DHEA-, delta4-androstenedione-induced testosterone secretion and StAR, 3beta-HSD, cytochrome P-450scc and P-450c17 mRNAs. hCG binding sites and LH/hCG receptor mRNA were slowly down regulated by r-hLH, reaching 47+/-1 and 18+/-7% of control at 24 h, respectively. Down-regulation of both hCG- and cholera toxin-induced cAMP production occurred earlier and was more marked, and at 24 h represented only 2.7+/-0.5 and 12.5+/-3.6% of control. Due to the synergistic effect of r-hLH and forskolin on cAMP production, the forskolin-induced cAMP was higher in r-hLH treated than in control cells, but this response also declines with time and was, at 24 h, only 32% of that observed at 30 min. This decreased cAMP production was associated with a less marked decline in the amount of membrane content of Galphas protein. The testosterone production in response to hCG, cholera toxin, forskolin and 8Br-cAMP declined to reach a nadir at 6 h but increased thereafter and at 24 h was significantly higher than in control cells. In contrast, the conversion of several precursors into testosterone remained stable or increased slightly during the first hours of r-hLH treatment and significantly increased at 24 h and this was associated with an increase of StAR, 3beta-HSD, P-450scc and P-450c17 mRNAs. Taken together, the present results indicate that, despite the marked down-regulation of transmembrane signaling, r-hLH increased the steroidogenic capacity of Leydig cells by increasing the expression of several genes encoding the proteins involved in testosterone synthesis.


The borderline dysplastic hip: when and how is it abnormal?
Borderline acetabular dysplasia refers to mildly sub-normal patterns of acetabular shape and coverage that might predispose children to mechanical dysfunction and instability. Borderline dysplasia generally includes children with a lateral center edge angle (CEA) of 18-24°. Some children with borderline radiographic measurements have normal joint mechanics and function while others benefit from acetabular reorienting surgery. Although radiographic findings of borderline dysplasia might suggest instability, the ultimate diagnosis is based on history and physical exam in addition to imaging. Children with borderline acetabular dysplasia sometimes benefit from other cross-sectional imaging studies such as MR imaging to evaluate for secondary evidence of instability, including damage along the acetabular rim, or labral degeneration and hypertrophy. CT is also helpful for depiction of 3-D acetabular morphology for preoperative assessment and planning. Pediatric radiologists are often the first to identify borderline or mild dysplasia on radiographs. It is imperative that pediatric radiologists serve as effective consultants and offer appropriate recommendations as part of a cohesive multidisciplinary approach to this complex patient population.


Evidence for glucuronidation and sulfation of zeranol and metabolites (taleranol and zearalanone) by rat and pig hepatic subfractions.
Biochemical evidence is given of alpha-zearalanol (zeranol), zearalanone, and beta-zearalanol (taleranol) glucurono- and sulfoconjugation in the rat and pig. It is based on the use of liver microsomal and cytosolic fractions, incubation with labeled endogenous coupling substrates, i.e. UDP-glucuronic acid and sulfate, and HPLC profiling of the resulting incubates. It is proved that only monoconjugates are produced, while it is suggested that conjugation occurs on the aromatic ring. Whether it is the C-14 or C-16 hydroxyl group that is conjugated remains to be demonstrated. When comparing the metabolic profiles in vitro with those already obtained in pig plasma, it can be concluded that both glucurono- and sulfoconjugates are produced in vivo.


Characterization of the anticoagulants from Taiwan cobra (Naja naja atra) snake venom.
Taiwan cobra (Naja naja atra) snake venom was separated into 19 fractions by means of CM-Sephadex C-50 column chromatography. Anticoagulant Fractions V-VII were refractionated by gel filtration on Sephadex G-50 and the purified component possessed phospholipase A2 activity and an inhibitory effect on collagen-induced platelet aggregation. The anticoagulant action could be antagonized by phospholipid or platelet factor 3. Anticoagulant Fraction XVII was also further refractionated by gel filtration on Sephadex G-50 and the purified component was shown to be cardiotoxin. It was a weak anticoagulant, caused direct hemolysis and potentiated collagen-induced platelet aggregation. Thromboelastographic studies showed that the anticoagulant action of cobra venom is due to the synergistic effects of phospholipase A2 and cardiotoxin.


Central serous chorioretinopathy: Professional repercussions among agents of the internal security forces.
To describe the relationship between central serous chorioretinopathy (CSCR) and stress in addition to the transient and permanent professional repercussions of this condition among security forces agents. This is a retrospective, descriptive study of 22 CSCR patients. All patients were interviewed to establish their job status, a stressful triggering event, the number of consultations, absenteeism, the duration of episodes, the number of days off, exemption from certain activities and professional reclassification. All of our patients underwent a complete ophthalmological examination and ancillary testing (OCT optical coherence tomography, fluorescein retinal angiography) to establish the positive diagnosis and to determine the clinical form. During their daily activity, all patients were armed and worked night security duty. They all reported a stressful event just before the onset of the disease. The average visual acuity was 4/10 P6 all forms combined; with a visual acuity between 1 and 2/10 for the chronic form. Visual impairment was associated with absenteeism (mean length of time off was 1.13 months per episode), exemptions from carrying arms or night duty in 36.36% of cases, with professional reclassification in 22.7% of patients. CSCR affects psychology and alters the quality of life of patients who are generally young and professionally active. This can interfere with work performance and cause temporary or permanent disability.


Detection of circulating hepatitis B virus immune escape and polymerase mutants among HBV-positive patients attending Institut Pasteur de Bangui, Central African Republic.
Previous studies in the Central African Republic (CAR) have reported the presence of hepatitis B virus (HBV) recombinant genotype E/D and a suspicion of immune escape mutants (IEMs), without further investigation into their impact on prevention and diagnosis. Consequently, this study investigated HBV mutations among hepatitis B surface antigen (HBsAg)-positive patients attending Institut Pasteur de Bangui in the CAR. Sera from a total of 118 HBsAg-positive patients with no previous history of HBV treatment or vaccination at the Institut Pasteur de Bangui, were sampled between 2017 and 2019. Subsequently, the region spanning the surface and polymerase genes of HBV was amplified by PCR and sequenced. HBV sequences were genotyped/subgenotyped by phylogenetic analysis and serotyped based on predicted amino acid residues at positions s122, s127, s140, s159, and s160. They were then analyzed for HBV IEMs and polymerase mutations. The region spanning the surface and polymerase genes was successfully amplified and sequenced for 51 samples. Of the HBV sequences, 49 were genotype E and two were genotype A subgenotype A1; these were serotyped as ayw4 and ayw1, respectively. Potential IEMs sY100C, sA128V, and sM133T, and several polymerase mutants were identified. This study raises awareness of the need for further studies to be conducted on a large scale to better understand HBV mutations for improved disease control and prevention strategies in the country.


CLABSI Rounding Team: A Collaborative Approach to Prevention.
Central line-associated bloodstream infections (CLABSIs) are an ongoing concern in health care, resulting in increased mortality, morbidity, length of stay, and additional costs to hospitals. Despite intermittent improvements in CLABSI rates within our facility, long-term sustainment has been challenging. This was a quality improvement project including a collaborative rounding approach supported by specialty nursing roles. In addition to implementing a variety of evidence-based interventions, the rounding team performed audits to assess performance and created focused education tools to address the identified opportunities within each individual unit. High levels of engagement as evidenced by increased audit completion resulted in CLABSI reductions. However, 2 peaks in CLABSI rates were associated with higher volumes of coronavirus disease (COVID-19) hospitalizations and decreased audits. Despite challenges correlated with COVID-19, a collaborative rounding team promotes and enhances awareness of prevention methods and a culture of safety.


Clinical trials, genetic add-ons, and the question of benefit-sharing.
Discussion of benefit-sharing has become common in the sphere of human genetic research. Roughly, this term means that individuals or organisations who could reap financial rewards from research into human genetics have some obligation to share the benefits of this research, perhaps with the people who made the research possible in the first place, or with humankind more broadly. This idea has met with some acceptance, finding its way into policy recommendations and statements of several prominent groups. However, the issue of benefit-sharing is generally raised in the context of large-scale population-based genetic studies. Other sources of human DNA are often ignored. In particular, little attention has been paid to the increasingly common practice of collecting genetic samples as add-ons to clinical drug trials. Generally such trials do not specify a use for these samples, which are collected for purposes of potential future research. We argue that if a case for benefit-sharing can be made for genetic studies in general, it can be made for add-on studies as well. We suggest some ways in which benefit-sharing might be implemented for genetic add-on studies.


Coupling effect of vehicle wake and jet flow on the dispersion characteristics and dilution efficiency of pollutants in urban highway tunnels.
The pollutants emitted by traveling vehicles are prone to accumulation inside urban highway tunnels, which poses a serious threat to the driving safety and health of passengers. This study employed the dynamic mesh method to simulate a traveling vehicle and investigated the coupling effect of vehicle wake and jet flow on the dispersion characteristics of pollutants in urban highway tunnels. To ensure the accuracy of the numerical simulation results, the turbulence model (realizable k-ε model) and dynamic mesh model were validated through field tests. The results revealed that jet flow can disrupt the large-scale longitudinal vortices pattern in the wake region, whereas vehicle wake can simultaneously weaken the entrainment strength of jet flow. The jet flow was found to be decisive in the space with a height greater than 4 m, whereas the vehicle wake intensity was considerably stronger at the bottom space of the tunnel, leading to the accumulation of pollutants in the passenger breathing zone. To evaluate the effect of jet fans on pollutants in the breathing zone, an innovative dilution efficiency was proposed. The dilution efficiency can be significantly affected by the intensity of vehicle wake and turbulence. Moreover, the dilution efficiency of alternative jet fans was better than that of traditional jet fans.


The effects of stimulation of trigeminal sensory afferents upon caudate units in cats.
This investigation assessed the influences of trigeminal primary sensory afferents upon caudate neuronal activity in locally anesthetized and chloralose anesthetized cats. Afferents from jaw elevator stretch receptors were stimulated via electrodes in the trigeminal mesencephalic nucleus (Mes 5). Afferents from dental and periodontal receptors were stimulated via electrodes in the inferior dental nerve (IDN). Low intensity electrical stimulation of either locus evoked caudate neuronal responses with Mes 5 being more effective. Higher intensity stimulation of IDN in chloralose anesthetized cats was used to determine if thresholds of trigeminal evoked caudate responses corresponded to thresholds of particular fiber groups in the sensory afferent. In all tested units, neuronal responses were only evoked when stimulation was suprathreshold for both A beta and A delta fibers. These data were discussed in relation to processing of oropharyngeal sensory information within the basal ganglia. Possible implications for bucco-lingual dyskinesias were noted.


Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure.
Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF, GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.


Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast Cancer: A Systematic Review.
Breast cancer (BC) is the most common neoplasm in women worldwide. Liquid biopsy (LB) is a non-invasive diagnostic technique that allows the analysis of biomarkers in different body fluids, particularly in peripheral blood and also in urine, saliva, nipple discharge, volatile respiratory fluids, nasal secretions, breast milk, and tears. The objective was to analyze the available evidence related to the use of biomarkers obtained by LB for the early diagnosis of BC. Articles related to the use of biomarkers for the early diagnosis of BC due to LB, published between 2010 and 2022, from the databases (WoS, EMBASE, PubMed, and SCOPUS) were included. The MInCir diagnostic scale was applied in the articles to determine their methodological quality (MQ). Descriptive statistics were used, as well as determination of weighted averages of each variable, to analyze the extracted data. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) are described. In this systematic review (SR), 136 articles met the selection criteria, representing 17 709 patients with BC. However, 95.6% were case-control studies. In 96.3% of cases, LB was performed in peripheral blood samples. Most of the articles were based on microRNA (miRNA) analysis. The mean MQ score was 25/45 points. Sensitivity, specificity, and area under the curve values for specific biomarkers (individual or in panels) have been found. The determination of biomarkers through LB is a useful mechanism for the diagnosis of BC. The analysis of miRNA in peripheral blood is the most studied methodology. Our results indicate that LB has a high sensitivity and specificity for the diagnosis of BC, especially in early stages.


Is there tea complemented with the appealing flavor of microplastics? A pioneering study on plastic pollution in commercially available tea bags in Bangladesh.
Microplastic pollution is a global concern, mainly due to its adverse effects on organisms and ecosystems. However, our knowledge of its impact on humans, in particular, is still very limited. Thus, while we have not gathered definitive information on their consequences, studies that aim to identify the MP's sources constitute subsidies to better understand the various exposure pathways to these pollutants. Thus, we investigated the possible presence of MP-like particles in teabag samples (of different brands) obtained in Dhaka, Bangladesh. Surprisingly, all analyzed samples (five brands) were contaminated with MPs. Fragments and fibers were identified in a higher percentage, and a wide variety of colors was identified, with a predominance of brown, blue, and red colors. Scanning electron microscope images of teabags exhibited net-like structures of fiber particles with a smooth surface. Furthermore, we observed irregularly shaped MPs and rougher surfaces and fragments in the process of detachment from the main fiber, oxidation flakes, and fracture-like. The average size of these pollutants was between 200.6 and 220.7 μm, and the polymer types identified via Fourier-transform infrared spectroscopy (FT-IR) were polytetrafluoroethylene, high-density polyethylene, polycarbonate, nylon, polyvinyl chloride, polytetrafluoroethylene, ethylene-vinyl acetate, cellulose acetate, and acrylonitrile butadiene styrene, the last three being the most frequent in the analyzed samples. Finally, we noticed that MPs from tea bags in Dhaka could cause an average emission of 10.9 million grams of MPs/year. Although the teabags analyzed in our study are not "complemented with the appealing flavor of MPs", it is very likely that tea ingestion in Dhaka is accompanied by the concomitant ingestion of plastic particles making teabags an important route of human exposure to these micropollutants.


Adenosine deaminase and 5'nucleotidase activities in peripheral blood T cells of multiple sclerosis patients.
Multiple sclerosis (MS) is one of the most common causes of neurological disability in young and middle-aged adults and is thought to be mediated by autoreactive T cells. Activities of adenosine deaminase (ADA) and 5'(nucleotidase (5'NT), which are involved in the differentiation and maturation of the lymphoid system, were measured in peripheral blood T cells from 21 MS patients and in 23 age and sex matched healthy controls to determine whether an association existed between these enzyme abnormalities and cellular immune functions. ADA and 5'NT activities were found significantly decreased in MS patients (P < .001 and P < .01 respectively) when compared with controls. Low levels of ADA and 5'NT activities were found irrespective of whether patients had relapsing-remitting or chronic progressive MS. These findings suggest that low levels of these enzyme activities in T cells may be related to the persistent abnormalities in T cell function in the clinical course of MS.


Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke.
C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis. We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes. All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS. Chinese Clinical Trial Registry, ChiCTR1800020330.


Screening performance of different methods defining fetal nasal bone hypoplasia as a single and combined marker for the detection of trisomy 21 in the second trimester.
To evaluate different methods of defining fetal nasal bone hypoplasia in the second trimester for the detection of trisomy 21. Prospective study in Greek women undergoing anomaly scan between 18 + 0 and 23 + 6 weeks. The following methods of defining nasal bone hypoplasia were evaluated, either as a single marker or in combination with others: (1) BPD to nasal bone length (NBL) ratio; (2) multiples of the median (MoM) of NBL, according to normal curves from a Greek population; (3-4) NBL < 2.5 percentile according to normal curves (3) commonly used internationally curves and (4) curves from a Greek population. In total, 1301 singleton fetuses were evaluated - 10 with trisomy 21. The best detection rate of trisomy 21 was achieved when the applied method was nasal bone percentiles adjusted to maternal ethnicity, in combination with other markers (<2.5 percentile according to normal curves from a Greek population; p < 0.001; sensitivity 50%; specificity 94.8%; false-positive rate 5.2%; positive likelihood ratio 9.6). Screening performance of fetal nasal bone hypoplasia in detecting trisomy 21 varies according to the method applied. The best screening performance is achieved by using percentiles adjusted to maternal ethnicity in combination with other markers of aneuploidy.


Is there a future for clinical laboratories? Experience in the Marche Region, Italy.
The government of the Marche Region has approved an Act called the "Regional Health Plan" establishing rules for the organization and development of healthcare. The main aim of the general plan is to rationalize the activities of medical laboratories first by making up an inventory of existing facilities and tests performed, and by classifying laboratories on the basis of their specialization and the complexity of tests that they perform.Moreover, the possible role of point-of-care testing and the need for clinical advice by laboratory professionals has also been debated.


Proteomic analysis of extracellular vesicles reveals an immunogenic cargo in rheumatoid arthritis synovial fluid.
Extracellular vesicles (EVs) from rheumatoid arthritis (RA) synovial fluid (SF) have been reported to stimulate the release of pro-inflammatory mediators from recipient cells. We recently developed a size exclusion chromatography (SEC)-based method for EV isolation capable of high-quality enrichments from human SF. Here, we employed this method to accurately characterise the SF EV proteome and investigate potential contributions to inflammatory pathways in RA. Using our SEC-based approach, SF EVs were purified from the joints of RA patients classified as having high-level (n = 7) or low-level inflammation (n = 5), and from osteoarthritis (OA) patients (n = 5). Protein profiles were characterised by mass spectrometry. Potential contributions of EV proteins to pathological pathways and differences in protein expression between disease groups were investigated. Synovial fluid EVs were present at higher concentrations in RA joints with high-level inflammation (P-value = 0.004) but were smaller in diameter (P-value = 0.03) than in low-level inflammation. In total, 1058 SF EV proteins were identified by mass spectrometry analysis. Neutrophil and fibroblast markers were overrepresented in all disease groups. Numerous proteins with potential to modulate inflammatory and immunological processes were detected, including nine citrullinated peptides. Forty-five and 135 EV-associated proteins were significantly elevated in RA joints with high-level inflammation than in RA joints with low-level inflammation and OA joints, respectively. Gene ontology analysis revealed significant enrichment for proteins associated with 'neutrophil degranulation' within SF EVs from RA joints with high-level inflammation. Our results provide new information about SF EVs and insight into how EVs might contribute to the perpetuation of RA.


Puberty in cystic fibrosis.
Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the majority of individuals with CF. However, youth with more severe disease are still at risk for delayed puberty. Careful evaluation of pubertal development in children and adolescents with CF is important as pubertal timing impacts linear growth, bone mineral accrual, body image and psychosocial wellbeing, all of which can also be impacted directly by CF. This article reviews the physiology of puberty, timing of puberty in CF, evaluation of pubertal development, and the differential diagnosis, evaluation, and management of delayed and precocious puberty in people with CF.


Gender attitudes and health risk behaviors in urban African American and Latino early adolescents.
This study examines the association of beliefs about gender differences (frequently termed gender attitudes or attitudes about women in other research) and of beliefs specifically about masculinity to health risk behaviors in minority, urban, early adolescents, in light of the "gender conventionality" hypothesis. Data from a self-administered questionnaire assessing gender attitudes and violence-related, substance use, and heterosexual health risk behaviors administered to 587 African American and Latino early adolescents are analyzed. With sociodemographic and family variables controlled, in males violence-related behaviors and substance use are associated with traditional beliefs about masculinity, and heterosexual activity is associated with traditional beliefs about gender differences. In females, being sexually active is positively associated with traditional beliefs about masculinity. Interventions to reduce health risk behaviors in minority, urban, early adolescents may be more effective if they include greater attention to ways in which gender-related attitudes may play a role in health risk taking.


Pulmonary Artery Dual-Lumen Cannulation Versus Two Cannula Percutaneous Extracorporeal Membrane Oxygenation Configuration in Right Ventricular Failure.
Refractory right ventricular failure has significant morbidity and mortality. Extracorporeal membrane oxygenation is indicated when medical interventions are deemed ineffective. However, it is still being determined if one configuration is better. We conducted a retrospective analysis of our institutional experience comparing the peripheral veno-pulmonary artery (V-PA) configuration versus the dual-lumen cannula with the tip in the pulmonary artery (C-PA). The analysis of a cohort of 24 patients (12 patients in each group). There was no difference in survival after hospital discharge (58.3% in the C-PA group compared to 41.7% in the V-PA group, p = 0.4). Among the C-PA group, there was a statistically significant shorter ICU length of stay (23.5 days [interquartile range {IQR} = 19-38.5] vs. 43 days [IQR = 30-50], p = 0.043) and duration of mechanical ventilation (7.5 days [IQR = 4.5-9.5] compared to (16.5 days [IQR = 9.5-22.5], p = 0.006) in the V-PA group. In the C-PA group, there were lower incidents of bleeding (33.33% vs. 83.33%, p =0.036) and combined ischemic events (0 vs. 41.67%, p = 0.037). In our single-center experience, the C-PA configuration might have a better outcome than the V-PA one. Further studies are needed to confirm our findings.


Billionaire's crypto company collapse strands scientists.
As FTX files for bankruptcy, the grantees its foundations supported may not see all of their pledged money.


Severe pancytopenia triggered by recombinant hepatitis B vaccine.
We describe the case of a teenager who developed fever, arthritis, cutaneous vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late myeloid elements and, subsequently, maturation arrest. Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells from the patient was dramatically increased. An underlying immune predisposition (HLA-DR3) may have indirectly enabled the vaccine to trigger a hepatitis B virus-specific cytotoxic T-lymphocyte response. It is therefore possible that the pancytopenia was induced by a dysregulation of the CD8+ T-cell compartment via increased IFN-gamma production.


Implications of altered inotropic effects of phenylephrine in pressure-overloaded cat ventricular muscle.
The positive inotropic action of phenylephrine in cardiac muscle is mediated by alpha- and beta-adrenoceptors. Data suggest the responsiveness of myocardium to inotropic agents is altered in cardiac disease. We evaluated the actions of phenylephrine on isometric contraction and K+-induced contracture in isolated cat right ventricular muscle from normal hearts and hearts with partial pulmonary artery ligation-induced pressure overload of 5-11 days in duration. Peak contractile force (Po) and rate of force development (dP/dt) were lower (p less than or equal to 0.005) in pressure-overloaded (0.59 +/- 0.2 g/mm2 and 4.6 +/- 1.7 g/s/mm2, respectively) than in normal (1.33 +/- 0.2 g/mm2 and 10.5 +/- 1.6 g/s/mm2, respectively) muscle. Phenylephrine (10(-6), 5 X 10(-6), and 10(-5) M) significantly (p less than or equal to 0.01) increased Po and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 X 10(-6) M) reduced peak K+-induced contracture force (Pc) similarly in normal (-30 +/- 8%) and pressure-overloaded (-36 +/- 11%) muscles. beta-Adrenergic blockade (nadolol, 10(-4) M) reduced, but did not abolish, the "relaxant" action of the drug on Pc in both muscle groups. The lack of a positive inotropic effect of phenylephrine in pressure-overloaded muscle suggests a derangement in both alpha- and beta-adrenoceptor function in this model of cardiac disease.


Normal T cell subsets and lymphocyte activity in multiple sclerosis.
Nine patients with either chronic progressive or relapsing/remitting multiple sclerosis were treated with several courses of lymphopheresis. The lymphocytes obtained by this procedure showed a significantly lower percentage of OKT3+ cells than normal controls at the beginning of therapy. This percentage increased to normal levels after five lymphopheresis treatments and then decreased during the last stages of treatment. Patients had normal levels of OKT4+ and OKT8+ cells compared to controls and these percentages showed no statistically significant changes during the course of treatment. The proliferative response of patient's lymphocytes after stimulation with concanavalin A, PHA and alloantigen was not significantly different from normal controls and these responses were unchanged during the lymphopheresis treatment. Natural killer cell activity was also normal in our patients. The results reported in this study do not suggest a basic T cell abnormality in our patients with multiple sclerosis. Furthermore, the lymphopheresis treatments did not induce any significant change in T cell numbers or functional activity in vitro.


Computational Fluid Dynamics Turbulence Model and Experimental Study for a Fontan Cavopulmonary Assist Device.
Head-flow HQ curves for a Fontan cavopulmonary assist device (CPAD) were measured using a blood surrogate in a mock circulatory loop and simulated with various computational fluid dynamics (CFD) models. The tests benchmarked the CFD tools for further enhancement of the CPAD design. Recommended Reynolds-Averaged Navier-Stokes (RANS) CFD approaches for the development of conventional ventricular assist devices (VAD) were found to have shortcomings when applied to the Fontan CPAD, which is designed to neutralize off-condition obstruction risks that could contribute to a major adverse event. The no-obstruction condition is achieved with a von Karman pump, utilizing large clearances and small blade heights, which challenge conventional VAD RANS-based CFD hemodynamic simulations. High-fidelity large eddy simulation (LES) is always recommended; however, this may be cost-inhibitive for optimization studies in commercial settings, thus the reliance on RANS models. This study compares head and power predictions of various RANS turbulence models, employing experimental measurements and LES results as a basis for comparison. The models include standard k-ϵ, re-normalization group k-ϵ, realizable k-ϵ, shear stress transport (SST) k-ω, SST with transitional turbulence, and Generalized k-ω. For the pressure head predictions, it was observed that the standard k-ϵ model provided far better agreement with experiment. For the rotor torque, k-ϵ predictions were 30% lower than LES, while the SST and LES torque values were near identical. For the Fontan CPAD, the findings support using LES for the final design simulations, k-ϵ model for head and general flow simulation, and SST for power, shear stress, hemolysis, and thrombogenicity predictions.


Unveiling the Potential of Liquid Biopsy in HER2-Positive Breast Cancer Management.
Invasive breast cancer (BC) is the most common cancer in women with a slightly increasing yearly incidence. BC immunohistochemical characterisation is a crucial tool to define the intrinsic nature of each tumour and personalise BC patients' clinical management. In this regard, the characterisation of human epidermal growth factor receptor 2 (HER2) status guides physicians to treat with therapies tailored to this membrane receptor. Standardly, a tumour solid biopsy is therefore required, which is an invasive procedure and has difficulties to provide the complete molecular picture of the tumour. To complement these standard-of-care approaches, liquid biopsy is a validated methodology to obtain circulating tumour components such as circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) from body fluids in an easy-to-perform minimal-invasive manner. However, its clinical validity in cancer is still to be demonstrated. This review focusses on the utilisation of both ctDNA and CTCs in early and metastatic HER2-positive BC tumours. We discuss recently published studies deciphering the capacity of liquid biopsy to determine the response to neoadjuvant and adjuvant therapies as well as to predict patients' outcomes.


An extra dimension in protein tagging by quantifying universal proteotypic peptides using targeted proteomics.
The use of protein tagging to facilitate detailed characterization of target proteins has not only revolutionized cell biology, but also enabled biochemical analysis through efficient recovery of the protein complexes wherein the tagged proteins reside. The endogenous use of these tags for detailed protein characterization is widespread in lower organisms that allow for efficient homologous recombination. With the recent advances in genome engineering, tagging of endogenous proteins is now within reach for most experimental systems, including mammalian cell lines cultures. In this work, we describe the selection of peptides with ideal mass spectrometry characteristics for use in quantification of tagged proteins using targeted proteomics. We mined the proteome of the hyperthermophile Pyrococcus furiosus to obtain two peptides that are unique in the proteomes of all known model organisms (proteotypic) and allow sensitive quantification of target proteins in a complex background. By combining these 'Proteotypic peptides for Quantification by SRM' (PQS peptides) with epitope tags, we demonstrate their use in co-immunoprecipitation experiments upon transfection of protein pairs, or after introduction of these tags in the endogenous proteins through genome engineering. Endogenous protein tagging for absolute quantification provides a powerful extra dimension to protein analysis, allowing the detailed characterization of endogenous proteins.


Can IQCODE detect poststroke dementia?
Little is known about the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in the screening of post-stroke dementia (PSDE). At 3 months after the index stroke, a research assistant administered the IQCODE to relatives of 189 Chinese patients with acute stroke who were consecutively admitted to a general hospital. A psychiatrist, who was blind to the IQCODE scores, interviewed all 189 patients and made DSM-IV diagnosis of dementia, which served as the benchmark for judging the performance of IQCODE in screening PSDE. The optimal cut-off point of IQCODE was 3.40. The sensitivity, specificity, and positive and negative predictive values of IQCODE, and the area under the receiver operating characteristic curve, were 88%, 75%, 33%, 98%, and 0.88, respectively. When used as a sole instrument, IQCODE does not appear to be useful in screening PSDE in Chinese elderly.


A Financing Strategy to Expand Surgical Health Care.
Despite an evolving need to provide surgical health care globally, few health systems, particularly in low-income and middle-income countries (LMICs), can sufficiently provide such care. The vast majority of the world's people-an estimated 5 billion-are unable to access safe and affordable surgical health care when they need it. This is a significant concern for global public health because the demand for these services is rising with the epidemiological and demographic transitions occurring worldwide. A principal driver of weak surgical health care services is a lack of adequate health system financing for surgical health care. This article examines the financing of surgical health care by analyzing global trends in health system financing, approaches to expand fiscal space for health, and empirical perspectives on the design, introduction, and scale-up of policies to improve surgical systems. We describe a surgical health care financing strategy, together with broader political and economic considerations, to provide policy recommendations to fund the expansion of surgical health care and an essential surgical package as part of universal health coverage in LMICs.


Clinical Development of Gene Therapies: The First Three Decades and Counting.
In the past three decades the field of gene therapy has made remarkable progress, surging from mere laboratory experiments to Food and Drug Administration (FDA)-approved products that bring significant reduction in disease burden to patients who previously had no therapeutic options for their serious conditions. Herein, we review the evolution of the gene therapy clinical research landscape and describe the gene therapy product development programs evaluated by the FDA in Investigational New Drug applications received in 1988-2019. We also discuss the clinical development programs of the first six oncolytic and gene therapy products approved in the United States.


Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland.
Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum adrenocorticotropic hormone (ACTH) levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated. To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes. SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time reverse transcription polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry, and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay. The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2-positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization, and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus positivity. Our study supports the tropism of SARS-CoV-2 for human pituitary and encourages exploration of pituitary dysfunction after COVID-19.


Anticoagulation Issues in Patients with AF.
The evaluation of the risk of stroke for individual patients with atrial fibrillation (AF) is a crucial factor in the decision to provide anticoagulation therapy. Novel oral anticoagulants, as compared with warfarin, are associated with a lower or similar rate of stroke and systemic embolism and a lower rate of hemorrhagic stroke. These drugs are administered at a fixed dose, have a shorter peak action and half-life, and do not require international normalized ratio monitoring. After a successful AF ablation, oral anticoagulation therapy discontinuation seems to be feasible in patients with a CHADS2 score greater than or equal to 2 and normal left atrial (LA) function. However, larger prospective randomized trials are needed to confirm the safety of this strategy.


Evidence of circadian rhythms in non-photosynthetic bacteria?
Examples of circadian rhythms have been described in eukaryotic organisms and in photosynthetic bacteria, but direct proof of their existence in other prokaryotes is limited and has been largely ignored. The aim of this article is to review existing evidence and to present preliminary results that suggest that the heterotrophic bacterium Pseudomonas putida shows regular variations in its growth pattern synchronized with light/darkness cycles. We put forward the hypothesis that circadian regulation of certain processes can take place in non-photosynthetic prokaryotes and may represent an adaptative advantage in specific environments.


Correlation between Ultrasound Elastography and Histologic Characteristics of Papillary Thyroid Carcinoma.
The aim of this study was to investigate the correlation between elastography and histologic characteristics including fibrosis and calcification. We also wanted to investigate whether other clinicopathologic indexes influence the strain ratio (SR) of papillary thyroid carcinomas (PTCs). We retrospectively reviewed 126 papillary thyroid carcinomas (PTCs) from 103 patients who underwent ultrasonography and elastography before surgery. The histologic characteristics and clinicopathologic indexes were compared with the SR of ultrasound elastography (UE). The results showed that there was a significantly positive correlation between fibrosis degree and SR measurements (r = 0.754, p = 0.000); the SR was significantly different between the groups with and without calcification (11.34 ± 10.08 vs. 6.81 ± 7.33, p = 0.000). The standard coefficients of collagen and stromal calcification were 0.684 and 0.194, respectively. There was no significant correlation between SR and indices such as size, position, co-existence with Hashimoto's thyroiditis (HT), multifocality or cervical lymph node (CLN) metastasis. In conclusion, we found that the SR of UE is positively correlated with the fibrosis of PTC. Stromal calcification will elevate the SR dramatically, but psammoma bodies will not when they exist in the absence of stromal calcification.


Treatment of circumscribed choroidal hemangiomas.
Forty of 59 patients with a circumscribed choroidal hemangioma have been treated by photocoagulation since 1972 because of visual impairment due to secondary nonrhegmatogenous retinal detachment involving the fovea. An attempt was made in every case to bring about resolution of the subretinal fluid, but no attempt was made to destroy the tumor. The treatment techniques used were xenon arc photocoagulation and less intense argon laser photocoagulation. At least a temporary reduction or resolution of subretinal fluid occurred after treatment in most of the eyes, but subsequent reaccumulation of subretinal fluid was noted in many cases. Unfortunately, only 22.5% of the treated eyes retained visual acuity of 6/12 or better after an average follow-up of four years.


Hydrocortisone decreases the internalization of low density lipoprotein in cultured human fibroblasts and arterial smooth muscle cells.
The effect of hydrocortisone on the cellular low density lipoprotein (LDL) pathway was studied in cultured human skin fibroblasts and arterial smooth muscle cells. Hydrocortisone decreased both uptake and degradation of 125I-LDL, LDL binding, measured at 4 C, was not affected by the hormone. Physiological concentrations of hydrocortisone (4 . 1 X 10(-8) mol/l) resulted in a 30% reduction of LDL uptake and degradation which could not be accounted for by an effect of the hormone on macromolecular synthesis, cell protein or cell number. To test whether the decrease in uptake and degradation of 125I-LDL was due to reduced internalization, the effect of hydrocortisone on the internalization of prebound LDL was determined and found to be decreased. Also, preincubation with unlabelled LDL in the presence of hydrocortisone resulted in less down regulation of LDL receptor activity than when no hydrocortisone was present. An effect of the hormone on bulk phase endocytosis has been excluded, since hydrocortisone did not affect either LDL degradation by receptor negative cells or endocytosis of 14C-sucrose by normal skin fibroblasts. Thus, hydrocortisone impairs LDL catabolism by decreasing the internalization of LDL normally bound to its cell surface receptor. These results may be relevant to the pathogenesis of atherosclerosis in conditions associated with reduced cellular LDL catabolism.


[Effect of leucine-enkephalin on the interneuronal transmission of excitation].
In the experiments on non-anesthetized flaxedil-immobilized cats it has been shown that the injection of leucin-enkephalin (1 mg) into the lateral ventricle of the brain is followed by the inhibition of evoked potentials in the ventrolateral columns of the spinal cord and of segmental interneuronal transmission in the spinal cord as well as by the reduction of the amplitude of potentials in the S I zone of the brain cortex induced by the sciatic nerve stimulation. Naloxone (1 mg/kg, i.v.) prevented the effects of leucin-enkephalin. Methysergide pretreatment (2.5 mg/kg, i.p.) led to a decrease of leucin-enkephalin effect on the interneuronal transmission in the spinal cord. Leucin-enkephalin failed to change the amplitude of polysynaptic potentials of glosso-mandibular reflex integrated at the brain stem level.


Personality mediators of psychopathy and substance dependence in male offenders.
Psychopathy and substance dependence (SUD) is highly prevalent in incarcerated populations and tends to co-occur in the same individuals. The factors underlying this relationship are not clearly understood. The primary purpose of this study was to investigate whether two personality models mediate the relationship between psychopathy and substance misuse in male offenders. Ninety-two inmates in provincial correctional centers in New Brunswick completed questionnaires, including the Sensitivity to Reward Sensitivity to Punishment Questionnaire to measure behavioral activation and behavioral inhibition, the Substance Use Risk Profile Scale to measure anxiety sensitivity, introversion/hopelessness, sensation seeking and impulsivity, and the Psychopathic Personality Inventory-Revised to assess psychopathy levels. Results revealed that high impulsivity indirectly mediated the relationship between psychopathy and stimulant dependence. In addition, low anxiety sensitivity indirectly mediated the relationship between psychopathy and opioid dependence. Finally, impulsivity indirectly and inconsistently mediated the relationship between psychopathy and alcohol dependence. These results suggest that individuals with psychopathic traits are at increased risk of misusing certain drugs due to underlying personality-based differences.


Skin cancer: a growing health problem for children.
To explore childhood ultraviolet radiation exposure and skin carcinogenesis, review prevention practices, analyze indoor tanning trends, identify skin cancer prevention programs, and address the role of the oncology nurse in youth-focused community initiatives. Review of the literature, research, and experience. Skin cancer is an important health problem for children because it is initiated in childhood and melanoma is on the rise in this population. Nurses can play a pivotal role in reducing the burden of skin cancer through patient education, community outreach, and political action.


Microbial monomers custom-synthesized to build true bio-derived aromatic polymers.
Aromatic polymers include novel and extant functional materials although none has been produced from biotic building blocks derived from primary biomass glucose. Here we screened microbial aromatic metabolites, engineered bacterial metabolism and fermented the aromatic lactic acid derivative β-phenyllactic acid (PhLA). We expressed the Wickerhamia fluorescens gene (pprA) encoding a phenylpyruvate reductase in Escherichia coli strains producing high levels of phenylalanine, and fermented optically pure (>99.9 %) D-PhLA. Replacing pprA with bacterial ldhA encoding lactate dehydrogenase generated L-PhLA, indicating that the produced enzymes converted phenylpyruvate, which is an intermediate of phenylalanine synthesis, to these chiral PhLAs. Glucose was converted under optimized fermentation conditions to yield 29 g/l D-PhLA, which was purified from fermentation broth. The product satisfied the laboratory-scale chemical synthesis of poly(D-PhLA) with M w 28,000 and allowed initial physiochemical characterization. Poly(D-PhLA) absorbed near ultraviolet light, and has the same potential as all other biomass-derived aromatic bioplastics of phenylated derivatives of poly(lactic acid). This approach to screening and fermenting aromatic monomers from glucose exploits a new era of bio-based aromatic polymer design and will contribute to petroleum conservation and carbon dioxide fixation.


Cinacalcet attenuates hypercalcemia observed in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors.
Excessive secretion of parathyroid hormone-related protein (PTHrP) by tumors stimulates bone resorption and increases renal tubular reabsorption of calcium, resulting in hypercalcemia of malignancy. We investigated the ability of cinacalcet, an allosteric modulator of the calcium-sensing receptor, to attenuate hypercalcemia by assessing its effects on blood ionized calcium, serum PTHrP, and calcium-sensing receptor mRNA in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors. Cinacalcet effectively decreased hypercalcemia in a dose- and enantiomer-dependent manner; furthermore, cinacalcet normalized phosphorus levels, but did not affect serum PTHrP. Ribonuclease protection assay results demonstrated presence of PTHrP receptor, but not calcium-sensing receptor mRNA in C26-DCT tumors. The mechanism by which cinacalcet lowered serum calcium was investigated in parathyroidectomized rats (i.e., without PTH) made hypercalcemic by PTHrP. Cinacalcet attenuated PTHrP-mediated elevations in blood ionized calcium, which were accompanied by increased plasma calcitonin. Taken together these results suggest that the cinacalcet-mediated decrease in serum calcium is not the result of a direct effect on tumor cells, but rather is the result of increased calcitonin release. In summary, cinacalcet effectively reduced tumor-mediated hypercalcemia and corrected hypophosphatemia in mice. Further investigation of cinacalcet for treatment of hypercalcemia of malignancy is warranted.


Comparison of whole-body MR imaging and conventional X-ray examination in patients with multiple myeloma and implications for therapy.
Skeletal X-ray survey is the established method of diagnosis in patients with multiple myeloma; however, whole-body magnetic resonance imaging (wb-MRI) has become an important additional tool. The aim of this study was to compare the different patterns of infiltration on conventional X-ray examinations (X-ray survey) with findings from wb-MRI to subsequently determine the influence of wb-MRI on therapy changes. In 60 patients with a mean age of 65.1 +/- 11.7 years, wb-MRI examinations were correlated with a recent X-ray survey. The results were independently assessed by two radiologists and the patterns of infiltration were described in both modalities. Subsequently, the disease was staged according to Salmon and Durie and Salmon and Durie PLUS. Additionally, the influence of MRI on potential changes in therapy was assessed using a three-range Likert-type scale. In all, 480 skeletal regions were compared. In 183 skeletal regions, an increased degree of infiltration was identified on wb-MRI. Significant differences (p < 0.05) between the modalities could be found in the thorax, spine, pelvis, and both lower extremities. Based on wb-MRI, tumor stage was upgraded in 19 of the 60 patients using the Durie and Salmon PLUS classification. In ten out of these 19 patients (42%), the wb-MRI result was essential for making the decision to initiate further therapy due to the degree of infiltration, extramedullary tumor extension, and/or further risk of fracture. Whole-body MRI provides a more detailed assessment of the pattern of bone marrow infiltration and strongly influences therapeutic strategies.


Thermodynamic evaluation on chemical looping conversion of Cd- and Zn-contained phytoremediation plant with different CaO pathways.
With the development of phytoremediation for soil contamination, disposal of phytoremediation plant becomes a serious problem. Thermochemical conversion of phytoremediation plant can greatly reduce the volume and mass, meanwhile the clean and reusable utilization is realized. As one of the thermochemical conversion technologies, chemical looping (CL) offers a carbon negative way for clean utilization of biomass. In this technology, CaO has binary roles of heavy metal solidification and CO2 sorption for gasification enhancement. To assess the CaO pathway in CL of phytoremediation plant, two different CL processes are constructed and comparatively studied based on thermodynamic evaluation. The effects of different operating parameters on the products of gasifier (GR) and reduction reactor (RR) are compared and discussed. Results demonstrated that the CaO addition in GR is beneficial to the production of pure combustible gases. Increasing RR temperature can promote the chemical looping reactions in RR. Under lower temperature, CaO in RR can consume more CO2 leading to CO2 free environment. When it is higher than 850 °C, there is no effect of CaO in RR. Increasing the amount of OC in system can enhance the conversion of combustible gases. When αOC is higher than 0.3, the OC is reduced to a mixed state of Fe3O4 and FeO. When the CaO circulates only between GR and calciner, pure CO2 can be captured at the outlet of calciner. Existence of CaO is beneficial to retain Cd and Zn in solid phases. When the gasification temperature increases from 500 °C to 800 °C, the Cd(g) increases while Cd decreases in both CL1 and CL2. For a long lifetime of OC, CaO is suggested to circulates between GR and calciner.